Zia Choudhry, MD, PhD, MBA

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

Amid a flurry of conflicting reports concerning the efficacy of vitamin D for COVID-19 patients, a sense of consternation has emerged in the health care sector regarding its overall utility. Our medical team proposes that we embrace a cautious approach to the implementation of vitamin D – one that is preventive and not curative in scope.

Vitamin D plays a critical role in the restorative function of mental health. Low vitamin D levels correlate with mood disorders as well as the development of schizophrenia. In light of the rise in mental health dysfunction and the body of evidence examined to develop this article, we recommend that patients continue to incorporate regular vitamin D supplementation during the course of the pandemic with the goal of preventing deterioration of well-being. Recent studies have generally overlooked the role of vitamin D in mental health by primarily focusing on the immediacy of therapeutic management for medical disorders within the context of COVID-19.
 

What is the role of vitamin D in human physiology?

Vitamins play an integral role in homeostatic metabolism. Vitamin D, in particular, is intimately responsible for regulating the body’s underlying phosphorus and calcium balance, thereby facilitating bone mineralization.¹ As an immunomodulatory hormone, vitamin D coordinates activities across innate and adaptive immune systems, providing defense against autoimmune diseases and miscellaneous infections.²

It is uncommon for people to be affected with vitamin D deficiency in equatorial zones, yet an Indonesian study uncovered low vitamin D effects (hypovitaminosis D) in virtually all of the patients in its COVID-19 case series.³

Likewise, a study conducted in Spain indicated that a whopping 82.2% of the COVID-19 patients endorsed clinically deficient levels of vitamin D, often within the context of severe presentation. Those patients also expressed elevated inflammatory markers, namely, D-dimer and ferritin.⁴

Comparable studies across the globe continue to support a correlative, if not causative, role for hypovitaminosis D and susceptibility to COVID-19. Mental health awareness entails healthy emotional interactions, preservation of well-being, and the ability to govern one’s thoughts and actions in accordance with societal expectations against the backdrop of ongoing psychosocial stressors. Such awareness helps ensure that people can make resourceful choices and meaningful associations, and can handle stress. We know that mental health is pivotal in dictating one’s overall health. This article provides a detailed exploration of the dynamics of mental health, COVID-19, and vitamin D.
 

The rationale for vitamin D supplementation therapy in COVID-19

When it comes to respiratory tract infections (RTI) such as COVID-19, influenza, and pneumonia, considerable interest has been generated with respect to the therapeutic efficacy of vitamin D in the acute setting. Vitamin D, as an inflammatory modulator, exerts a protective effect in patients with RTI, especially in those with deviations from baseline vitamin D levels.⁵

What is the rationale for administering vitamin D supplementation therapy for COVID-19? It has been noted that emergent cases of COVID-19 arise during the autumn months for European countries⁶ and there is also a firmly established connection between the amount of solar radiation/UV exposure (or the lack thereof) and influenza outbreaks,⁷ further underscoring the relevance of vitamin D levels. Despite those observations, wholesale implementation of vitamin D therapy should not be used in the acute setting for conditions such as COVID-19 or pneumonia as it is not supported by evidence-based practices. Despite the compound’s inherent antimicrobial actions,⁸ four randomized clinical trials involving pediatric subjects failed to demonstrate a significantly beneficial response (for example, radiographic resolution) to adjunctive supplementation during the course of acute pneumonia symptomatology.⁹ Likewise, data collected from a randomized controlled trial confirmed the suspicion that high-dose vitamin D therapy has no tangible effect, tied to mortality or otherwise, on moderate or severe presentations of COVID-19.¹⁰

Revisiting vitamin D supplementation therapy for mental health patients with COVID-19

It is clear that recent studies have undermined the overall applicability of vitamin D therapy with respect to acute presentations of COVID-19. However, our team would like to underscore the importance of vitamin D supplementation with respect to maintenance of the integrity of underlying mental health processes.

Numerous studies (for example, cross-sectional, cohort, case-control) have uncovered a statistically significant relationship between vitamin D deficiency and depression, including variants such as postpartum and antepartum depression. It should be noted that the pathophysiology for those variables is not entirely known and that the overall clinical utility of supplementation therapy has not previously been recommended because of existing gaps in the literature.¹¹

In another prospective study involving a relatively small sample size, subjects with seasonal affective disorder (SAD) were either exposed to 10,000 IUs of vitamin D or phototherapy, and depression endpoints were evaluated via the Hamilton Rating Scale for Depression, the SIGH-SAD, and the SAD-8 depression scale. Improvements in 25-hydroxyvitamin D (25-OH D) levels correlated with improvements in depression metrics. However, subjects exposed to phototherapy sessions did not exhibit any meaningful improvements in clinical outcome.¹²

It is also possible that vitamin D deficiency is reflective of an overall poor nutritional status. People with schizophrenia have frequently been observed to have vitamin D deficiency with more than half of all patients also manifesting symptoms of osteoporosis, a condition that often necessitates vitamin D supplementation. The literature shows that the jury is still out regarding the applicability of vitamin D supplementation for schizophrenia patients, with numerous conflicting studies, including one randomized trial indicating an improvement in positive and negative symptoms as well as in the metabolic profile.¹³

However, in light of the rather large and growing body of evidence suggesting an increased risk of deterioration, psychological distress, and worsened prognosis during the pandemic coupled with the presence of medical and/or mental health morbidities, it would be sensible for psychiatric patients, especially those with preexisting deviations from baseline vitamin D levels, to consider vitamin D supplementation.

Vitamin D supplementation therapy, as a preventive, but not curative measure – one that is also low cost/high benefit – allows for the patient to be in a much better position from the perspective of her/his general health and nutritional status to tackle the ongoing psychosocial challenges of the pandemic and/or COVID-19 exposure.
 

Dr. Aman is a faculty member in the biology department at City Colleges of Chicago. She is a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF) in Montreal; fellow, medical staff development, American Academy of Medical Management; and master online teacher (MOT) at the University of Illinois at Chicago. Dr. Aman disclosed no relevant relationships. Dr. Islam is a medical writer for the IMCHF and is based in New York. He is a postdoctoral fellow, psychopharmacologist, and a board-certified medical specialist. He disclosed no relevant financial relationships. Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston and is affiliated with Sturdy Memorial Hospital in Attleboro, Mass. He is on the speakers bureaus/advisory boards of Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience. Mr. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry (Mr. Choudhry’s father) is chief scientific officer and head of the department of mental health and clinical research at the IMCHF. Dr. Choudhry has no disclosures.

References

1. van Driel M and van Leeuwen JPTM. Mol Cellular Endocrinol. 2017;453:46-51.

2. Charoenngam N and Holick MF. Nutrients. 2020 Jul 15;12(7):2097. doi: 103390/nu12072097.

3. Pinzon RT et al. Trop Med Health. 2020 Dec 20;48:102. doi: 10.1186/S41182-020-00277-w.

4. Hernández JL et al. J Clin Endocrinol Metab. 2021 Mar;106(3)e1343-53.

5. Martineau AR et al. BMJ. 2017;356:i6583. doi: 1136/bmj.i6583.

6. Walrand S. Sci Rep. 2021 Jan 21;11(1981). doi: 10.1038/s41598-021-81419-w.

7. Moan J. et al. Dermatoendocrinol. 2009 Nov-Dec;1(6):307-9.

8. Fabri M et al. Sci Transl Med. 2011 Oct 12;3(104):104ra102. doi: 10.1126/scitranslmed.3003045.

9. Slow S et al. Sci Rep. 2018 Sep 14;8(1):13829. doi: 10.1038/s41598-018-32162-2.

10. Berman R. “Study confirms high doses of vitamin D have no effect on COVID-19.” Medical News Today. 2021 May 4.

11. Menon V et al. Indian J Psychol Med. 2020 Jan-Feb;42(1):11-21.

12. Gloth 3rd FM et al. Nutr Health Aging. 1999;3(1):5-7.

13. Cui X et al. Mol Psychiatry. 2021 Jan 26. doi:10.1038/s41380-021-01025-0.

An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.¹

When ADLs become a matter of survival

For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).

Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.

The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
 

Resource diversion and mitigation strategies

Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.

Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.

Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).²
 

Resilience and recovery in a retrospective study

A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.

The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.

Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.³ Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, AD patients may prove to be unusually resilient with respect to the recovery process, which underscores the importance of early diagnosis and intervention.
 

Genetic and environmental susceptibility

One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.⁴

Transcending research design

The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.

To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).

Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.⁵

 

References

1. Ritchie K. KJZZ. 2020 Nov 16.

2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.

3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.

4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.

5. Alzheimers Dement. 2020 Apr;16(4):587-8.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.

Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.

An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.¹

When ADLs become a matter of survival

For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).

Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.

The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
 

Resource diversion and mitigation strategies

Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.

Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.

Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).²
 

Resilience and recovery in a retrospective study

A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.

The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.

Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.³ Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, AD patients may prove to be unusually resilient with respect to the recovery process, which underscores the importance of early diagnosis and intervention.
 

Genetic and environmental susceptibility

One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.⁴

Transcending research design

The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.

To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).

Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.⁵

 

References

1. Ritchie K. KJZZ. 2020 Nov 16.

2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.

3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.

4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.

5. Alzheimers Dement. 2020 Apr;16(4):587-8.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.

Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.

An alarming number of additional Alzheimer’s disease (AD) deaths have been reported across various states within the past several months, according to the Alzheimer’s Association. Centers for Disease Control and Prevention data indicate that no less than 31,000 additional people with the neurodegenerative condition had died from the beginning of the pandemic through the end of September 2020. We know that long-term care facilities have been hit hardest, and access to adequate and/or prompt testing has been cited as the most pressing issue during the onset of the pandemic.¹

When ADLs become a matter of survival

For individuals affected with Alzheimer’s disease and other types of dementia, performing routine tasks may seem cumbersome and overwhelming. Many of these patients are dependent upon caregivers and family support to facilitate their activities of daily living (ADLs).

Transitioning into the “new normal” set by the pandemic milieu is not an easy task for the average AD individual, because they are now expected to comply with numerous safety instructions (for example, maintaining hygiene, social distancing, etc.). They are also expected to monitor and communicate information about the onset of any suspected symptom to their caregiver or health care clinician.

The additional tasks added to their list of ADLs are particularly distressing given their already compromised short-term memory and overall cognitive decline. Individuals with AD may also be dealing with a host of psychobehavioral challenges, such as the presence of depression, anxiety, and/or agitation amid self-isolation. Enforced social isolation tied to COVID-19 may compound those issues.
 

Resource diversion and mitigation strategies

Unfortunately, any disruption in services within a long-term care setting may lead to a suboptimal therapeutic environment for patients. The Washington State LTC, for example, reported experiencing a case fatality rate (CFR) exceeding more than a third of its residents; essential staff and health care clinicians were duly affected from exposure to the virus (the risk of transmission increases considerably during transport between facilities). Access to personal protective equipment (PPE) might have been hindered by availability.

Another issue with far-reaching consequences is diversion of resources for urgent care. Health care professionals may simply not be readily available for those with chronic care needs because of the enormous scale of the impact of COVID-19 upon health care systems.

Continuity of therapy might include evaluations or follow-up services via teleconferencing modalities, but an exhaustive initial onsite physical examination is often necessary for accurate diagnostics and care. Medication management for the newly diagnosed AD or dementia patient necessitates a thorough screening process involving appropriate in-person blood or laboratory work. It is for this reason that clinicians will need to plan ahead by preparing a contingency plan with the corresponding mitigation strategies (for example, telemedicine, proposed solutions to anticipated disruption of services, extended support, and feedback from family members, etc.).²
 

Resilience and recovery in a retrospective study

A research team from Wuhan Red Cross Hospital in China performed a retrospective cohort study on a sample of patients (n = 42) to determine the severity and prognostic features of COVID-19 pneumonia; 19 AD patients (as per National Institute on Aging/Alzheimer’s Association diagnostic guidelines) were directly compared with 23 age-matched non-AD COVID-19 patients in a similar treatment context.

The study yielded some rather unexpected findings, namely, AD patients experienced remarkably shorter hospital stays and better appetites, especially with respect to their non-AD counterparts. This is even more puzzling when considering that previous studies indicated that dementia patients with concomitant COVID-19 pneumonia are twice as likely to die as those without neurodegenerative compromise.

Aside from a seemingly inexplicable interest in food, the observable positive changes may be attributable to such factors that are particular to the nursing home – residents have immediate access to health care services, which generally allows for timely diagnosis and care. However, the authors of the study speculate that the pathophysiological response of angiotensin-converting enzyme 2 (ACE2) confers to AD patients a therapeutic advantage as they have reduced expression.³ Despite the notoriously high mortality rates of COVID-19 pneumonia among the elderly population, AD patients may prove to be unusually resilient with respect to the recovery process, which underscores the importance of early diagnosis and intervention.
 

Genetic and environmental susceptibility

One of the more devastating observations about the ongoing pandemic environment is that a whopping 80% of dying patients committed to a long-term facility also include those with AD; it has been reported that almost half of all patients in nursing homes and related services have the neurodegenerative condition. The grim scenario is brought about by several factors, chief of which is the proximity of shared living arrangements within the context of a residential care setting. It should be noted that patients with AD exhibit comorbid conditions (for example, diabetes, cardiovascular disease, and/or respiratory issues) that immediately put them at high risk for COVID exposure. Interestingly enough, the ApoE4 genotype, which is associated with an increased susceptibility for AD, is also correlated with COVID-19 prognosis and severity. Although exact numbers are difficult to come by, it is of utmost importance for clinicians to evaluate the overall scope of the situation, identify at-risk patients such as individuals with AD and related dementias, and work with caregivers to afford care to patients who need it the most.⁴

Transcending research design

The elderly population, unsurprisingly, experiences the highest COVID-19 mortality rate because of the presence of multiple risk factors, namely, compromised immunity and difficulties maintaining ADLs, and thereby adhering to safety protocols. As far as Alzheimer’s patients are concerned, numerous hurdles affect the domain of neurodegenerative research.

To safeguard the health and well-being of the participants and caregivers, site sponsors and investigators must explore various communication avenues with the goal of facilitating health education (for example, mitigation strategies, adverse effects monitoring, etc.), as well as implementing contingency plans in the event that a site becomes inaccessible (for example, site closure, traveling regulations, lockdowns, etc.).

Alternatives such as telemedicine present viable solutions for ensuring completion of studies. Given the nature of the pandemic, there is a possibility that a research participant may contract the virus, necessitating a break from the established protocol. It is for this reason that site sponsors and corresponding regulatory bodies are advised to proactively engage in dialogue and transparent communications with respect to ensuing protocol deviations. Institutional Review Boards can expedite the review process by making the necessary changes in a timely manner.⁵

 

References

1. Ritchie K. KJZZ. 2020 Nov 16.

2. Brown EE et al. Am J Geriatr Psychiatry. 2020 Jul;28(7):712-21.

3. Li J et al. J Alzheimers Dis. 2020;77(1):67-73.

4. Perry G. J Alzheimers Dis. 2020 Jan 1;76(1):1.

5. Alzheimers Dement. 2020 Apr;16(4):587-8.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships.

Dr. Dhillon is a staff neurologist at Brigham and Women’s Hospital in Boston. Dr. Dhillon is currently on the speaker bureau/advisory board for Biogen, Bristol Myers Squibb, Genzyme, and Teva Neuroscience.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He has no disclosures.

In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,¹ so much so that even propafenone is being mislabeled as the agent.² It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.

Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).^3,4

Addressing the challenge of imitation Percocet pills

Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.⁵As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.

However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.

Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.⁶ Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).

Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.^7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.⁹

As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.

A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
 

Treatment recommendations

According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.

Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.¹⁰ Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
 

References

1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.

2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.

3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.

4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.

5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.

6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.

7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.

8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.

9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.

10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.

In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,¹ so much so that even propafenone is being mislabeled as the agent.² It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.

Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).^3,4

Addressing the challenge of imitation Percocet pills

Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.⁵As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.

However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.

Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.⁶ Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).

Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.^7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.⁹

As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.

A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
 

Treatment recommendations

According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.

Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.¹⁰ Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
 

References

1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.

2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.

3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.

4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.

5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.

6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.

7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.

8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.

9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.

10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.

In recent years, Percocet (oxycodone/paracetamol) has experienced a meteoric rise to prominence because of the presence of conspicuous references in pop culture and the ever-evolving hip-hop scene,¹ so much so that even propafenone is being mislabeled as the agent.² It is of utmost importance for clinicians to be made aware of the adverse effects and the treatment protocols associated with Percocet as well as propafenone.

Propafenone is identified as a class 1C antiarrhythmic with adverse effects associated with that particular class of drugs (e.g., generalized tonic-clonic seizures coupled with widened QRS complex), however, Percocet’s toxidrome is the product of the opioid/nonopioid (in the form of oxycodone/acetaminophen) components found within the formulation. Percocet is often recreationally used with MDMA (“molly”) or ecstasy as popularized by the lyrics of “Mask Off” by Future (“Percocets, Molly, Percocets”).^3,4

Addressing the challenge of imitation Percocet pills

Differentiating the untoward effects of Percocet and propafenone isn’t too challenging because the agents belong to separate classes – the problem is the use of deceitful labels on propafenone with both medications sporting the “512 imprint” on their respective pills. Initial symptoms of propafenone ingestion may include weakness and dizziness followed by seizures.⁵As an emergent situation, the patient should be immediately treated with a sodium bicarbonate infusion to effectively reverse the sodium channel blockade associated with the widened QRS.

However, a more likely scenario is that of Percocet counterfeit pills designed to illicitly emulate the properties of officially marketed Percocet. As expected, Percocet overdose management will require that the clinician be familiar with treating general opioid toxicity (in this case, derived from the oxycodone component), in particular respiratory or CNS depression. Symptoms of opioid overdose also include the loss of consciousness with pupillary miosis. Therapy entails the use of naloxone and/or mechanical ventilation for respiratory support. The patient can also exhibit cardiovascular compromise. If further information is elicited during a patient interview, it may reveal a history of drug procurement from the streets.

Epidemiologists from Georgia collaborated with the state’s department of public health’s office of emergency services, forensic experts, and drug enforcement professionals to evaluate almost 40 cases of counterfeit Percocet overdoses during the period spanning the second week of June 2017. Of these cases, a cluster triad was identified consisting of general opioid toxicity symptoms (for example, CNS or respiratory depression with concomitant pupillary constriction, a history of drug procurement, and a history of ingesting only one or two pills with rapid deterioration.⁶ Unfortunately, the screening process is often hindered by the fact that synthetic opioids such as Percocet are not readily identified on urine drug screens (UDS).

Despite shortcomings in assessment procedures, a UDS will yield positive results for multiple drugs, a feature that is common to seasoned opioid users and serves as an instrumental diagnostic clue in the investigative process. To address the crisis and prevent further spread, numerous Georgia agencies (e.g., drug trafficking and legal authorities) worked with the health care community to expediently identify cases of interest and bring forth public awareness concerning the ongoing perils of counterfeit drug intake. Future investigations might benefit from the implementation of DNA-verified UDS, because those screens are versatile enough to detect the presence of synthetic urine substitutes within the context of opioid use.^7,8 Moreover, an expanded panel could be tailored to provide coverage for semisynthetics, including hydrocodone, oxycodone, hydromorphone, and oxymorphone.⁹

As a well-received painkiller from the opioid family, Percocet derives its analgesic properties from the fast-acting oxycodone; hepatic failure is also possible from Percocet (because of the acetaminophen component) or counterfeit Percocet overdose but is less common unless the Tylenol content approaches 4 grams. By binding to the brain’s opiate receptors, Percocet modulates pain pathways leading to a dulling of pain sensation along with euphoria, which is particularly attractive to drug seekers. Chronic Percocet use corresponds with a myriad of psychological and physical consequences, and the Drug Enforcement Administration recognizes oxycodone as a Schedule II drug.

A chronic Percocet user may try to disrupt the cycle of symptoms by abruptly ceasing use of the offending agent. This can precipitate the development of classical opioid-based withdrawal symptoms, including but not limited to nausea, vomiting, irritability, tachycardia, body aches, and episodes of cold sweats. Physicians have noted that misuse (i.e., deviations from intended prescribed) might include crushing and snorting as well as “doctor-shopping” behaviors for a continuous supply of Percocet.
 

Treatment recommendations

According to Sarah Wakeman, MD, medical director of the substance use disorders initiative at Massachusetts General Hospital in Boston, there are apparently two clinical manifestations of Percocet use. The primary consequence is derived from the oxycodone component of Percocet; as an opioid, oxycodone toxicity leads to disrupted breathing and oxygenation, negatively impacting vital organs such as the brain or the heart. Patients experiencing a lack of oxygen will often display cyanosis and may not respond appropriately to stimuli. For individuals suspected of succumbing to overdose, Dr. Wakeman reportedly advised that the clinician or trained professional rub his or her knuckles along the breastbone of the potential user – a drug overdose patient will fail to wake up. On the other hand, a Percocet user may exhibit the symptoms of liver failure depending on the overall level of acetaminophen in the formulation. To prevent relapses, Percocet use disorder is best managed in a professional setting under the direction of trained clinicians; users are provided medications to address ongoing cravings and symptoms associated with the withdrawal process. A detoxification center can tailor the treatment with opioid-based medications such as methadone, buprenorphine, and naltrexone to help patients be weaned off Percocet.

Clinicians may further improve the efficacy of a therapeutic regimen by incorporating a personalized plan with a comprehensive substance UDS panel for monitoring and treatment purposes. This may prove to be beneficial in the event of suspected polysubstance use, as is the case with patients who dabble with Percocet and “molly.” Preparations can also be instituted at the outset of therapy with genetic testing implemented in high-risk patients who exhibit an inclination for opioid use disorder.¹⁰ Genetic polymorphisms provide robust clinical assets for evaluating patients most at risk for relapse. For individuals with biological susceptibility, arrangements can be made to incorporate nonopioid treatment alternatives.
 

References

1. Thomas BB. The death of Lil Peep: How the U.S. prescription drug epidemic is changing hip-hop. The Guardian. 2017 Nov 16.

2. D’Orazio JL and Curtis JA. J Emer Med. 2011 Aug 1;41(2):172-5.

3. Levy L. These are the drugs influencing pop culture now. Vulture. 2018 Feb 6.

4. Kounang N and Bender M. “What is Percocet? Drug facts, side effects, abuse and more.” CNN. 2018 Jul 12.

5. The dangers of Percocet use and overdose. American Addiction Centers. Last updated 2020 Feb 3. https://americanaddictioncenters.org/percocet-treatment/dangers-of-use-and-overdose.

6. Edison L et al. MMWR. 2017 Oct 20;66(41):1119-20.

7. Choudhry Z et al. J Psychiatry. 2015. doi: 10.4172/2378-5756.10000319.

8. Islam F and Choudhry Z. Current Psychiatry. 2018 Dec;17(12):43-4.

9. Jupe N. Ask the Experts: DOT 5-panel drug test regimen. Quest Diagnostics. 2018 Mar 21. https://blog.employersolutions.com/ask-experts-dot-5-panel-drug-test-regimen/.

10. Ahmed S et al. Pharmacogenomics. 2019 Jun 28;20(9):685-703.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam reported no relevant disclosures. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He reported no relevant disclosures.

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

An intriguing pattern has emerged for cannabis enthusiasts as a result of lockdowns and statewide safety restrictions for COVID-19.

Consumers, as of late, have been shopping for larger marijuana baskets per trip to the dispensaries in various states, including California, Colorado, Nevada, and Washington, . However, they are also cutting down on the number of trips, perhaps, as a preventive measure to reduce the risk of exposure to coronavirus during this pandemic. Sales dipped considerably by the end of March only to experience a resurgence after the issuing of stimulus checks and unemployment benefits.

For the past few years, cannabis consumption remained steady while the industry continued to thrive with robust sales of the drug. It is a recession-proof phenomenon, therefore presenting a unique opportunity for clinicians with respect to patient education and individualized care.¹

An unfortunate carryover of the governmental restrictions, self-isolation, and social estrangement is that consumers are now turning to the dark web as a source for continuous supply of cannabis. Prepandemic, according to the U.N. 2020 World Drug Report, there was already a 30% increase in sales of cannabis between 2009 and 2018. COVID-19 has fractured the drug’s supply chain and created an inescapable void that is being filled by drug traffickers.² A clinical dilemma is posed when a user procures counterfeit cannabis or a drug batch with impurities.
 

Riding the cytokine storm

Cytokines are a host of proteins with designated regulatory and immune responses that play an instrumental role in cell signaling. The aptly named “cytokine storm” conjures up the image of an imperiled immune system spiraling out of control; it is, in fact, an extreme immune response that culminates into a massive influx of cytokines released into the bloodstream. Without the presence of an immunologic threat, cytokines are responsible for maintaining homeostasis and the functionality of immune cells. However, acute cytokine release (i.e., cytokine storm), as is the case with severe COVID-19, jeopardizes organ function (for example, interstitial lung disease) with clinical symptoms, such as fever, cough, dyspnea, and myalgia.

Benefits and drawbacks of immunosuppressive agents

To inhibit cytokine release (e.g., interleukin-6 cytokine levels), immunosuppressive agents such as tocilizumab have been leveraged to damper the body’s overactive inflammatory response to perceived immunologic stressors, in particular, COVID-19. While the aforementioned agent was remarkably effective with respect to lung consolidation clearance in most of the patients tested, a host of untoward effects prevent its general applicability and use. However, a team of researchers from the University of Nebraska, Omaha, with the Texas Biomedical Research Institute, San Antonio, might have stumbled upon a strategic workaround for mitigating the immune response.

They have proposed that cannabidiol (CBD) be used in lieu of other agents with potentially toxic effects. Animal and human trials have established that CBD confers a relatively high margin of safety coupled with favorable tolerance, providing a viable option for effectively targeting the inflammatory processes of SARS-CoV-2–based pulmonary disease. Furthermore, efficacy increased when CBD was combined with a terpene formulation, especially with respect to the more traditional steroid therapy.³

SARS-CoV-2 exhibits binding affinity for the ACE2 receptor, which is expressed in the lungs as well as other known predilection sites of infection. Ongoing studies attempt to modulate ACE2 expression, thereby eliminating its conspicuous role as “viral gateways,” perhaps even more so in patients with lung pathologies (e.g., people with chronic obstructive pulmonary disease [COPD] and smokers) as they already are prone to increased respiratory morbidity. CBD lacks tetrahydrocannabinol (THC), or the psychoactive component of cannabis sativa, rendering the agent to be particularly attractive from a therapeutic perspective. In addition to being devoid of abuse potential, CBD exhibits remarkable anti-inflammatory properties. It should be noted that considerable overlap exists between tobacco and cannabis users, and it is too early to determine the impact on COVID-19. As opposed to cannabis’s effect on ACE2 levels, smoking exhibits a proinflammatory role by up-regulating ACE2 expression.3 However, there are currently numerous conflicting reports in circulation about the positive effect of nicotine on COVID-19 outcome; confounding variables will need to be explored further in patients with a history of using nicotine and cannabis together.

From an immunologic perspective, the endocannabinoid system (ECS) plays an integral role in cell signaling by interacting with natural chemicals of the body, namely, cannabinoids with designated targets at the cannabinoid receptor 1 (CB1) and the CB2, respectively. The CB2 receptor is of particular interest as it is intimately involved in immune homeostasis; the primary goal of these COVID-19 studies is to modulate the endocannabinoid system via targeted CB2 therapies to produce an immunosuppressant effect.⁴ CB2 activation, be it by means of THC or CBD agonism, may prove to be beneficial by inhibiting the cytokine influx.

Unfortunately, there is a general dearth of data on COVID-19–exposed cannabis users, whether the drug is consumed for medication or recreational purposes. It has been suggested that cannabis intake might contribute toward the development of a cough, complicating the overall clinical outcome for those infected with the virus. The presence of a cough, even in an otherwise asymptomatic individual, facilitates viral spread. As for those cannabis users experiencing COVID-19 symptomatology, they can expect rapid clinical deterioration, including pronounced fatigue and a change in mental status.

According to pulmonary specialists and representatives of the American Lung Association, recreational cannabis use may be associated with a bronchitis-like inflammation (comparable with chronic bronchitis/COPD for chronic users) of the airways, along the lines of cigarette smoking.⁵ As far as cannabis smokers are concerned, the rationale for lung irritation is believed to stem from the relatively large portion of unburnt plant content that is inhaled in a given joint. If there is a superimposed infection, as is the case with COVID-19, the patient may experience further risk of adverse respiratory effects. This serves as a diagnostic dilemma for physicians, especially when they encounter patients who recently started dabbling with cannabis as a means of placating themselves or because they’ve heard rumors that it will somehow protect them from COVID-19. The entire assessment plan is slowed down as a result of the confounding variable (onset of a cough), which may arise independently of COVID-19 in cannabis users. Vulnerable populations include smokers and those with COPD or asthma, as they are more likely to require ventilator assistance during the course of COVID-19 therapy.⁵ Asthmatics and COPD patients are prone to bronchospasms because of sensitive airways.


 

COVID-19 safety protocols for cannabis users

Because of increased risk of respiratory morbidity, clinicians advise that consumption of recreational cannabinoids be scaled back during the course of the pandemic. In light of conflicting news from several media outlets regarding the efficacy of cannabis intake with respect to COVID-19, preexisting users might unwittingly increase their consumption as a preemptive measure against being exposed to the infection. To prevent transmission among users, clinicians should discourage patients from sharing joints. This recommendation is thematically consistent with general precautionary measures about the dangers of sharing utensils, drinking cups/glasses, and so on, amid the pandemic.

Despite promising preliminary research results, CBD cannot be wholeheartedly recommended at this time; patients already on medically administered cannabinoids are urged to discuss the risk-benefit ratio with their respective health care clinicians. Cannabinoid therapies present a massive opportunity from the perspective of immunomodulation, especially when considering the prevalence of drug use. However, to improve clinical guidelines with respect to COVID-19 outcomes, it would be prudent to increase the overall volume of preclinical knowledge by gathering retrospective data (from case-control designs) and randomized prospective trials.

A more comprehensive list of advice from physicians concerning casual or chronic cannabis users may also include: adopting a dedicated delivery or dispensing system for cannabis products, making considerations for decontamination (i.e., disinfecting mouthpieces), ensuring cleansing precautions are maintained (washing thoroughly before and after use or procurement), switching to inhalation alternates (e.g., tinctures, edibles, and/or oils) to decrease further irritation to the lungs. For bong users, it is recommended that they apply rubbing alcohol to clean their device followed with a minute of air-drying.⁶

Conclusion

The literature from preclinical studies appears to largely favor the use of CBD, but there remains an element of uncertainty with respect to implementing cannabinoids for the treatment of coronavirus.

COVID-19 cannabinoid intervention is a hot topic with renewed interest from the industry and the public at large, but viral-focused therapies remain a relatively underused area worth exploring with case-control designs and randomized prospective trials. As cannabis legalization is picking up momentum across five additional states, the time is ripe to systematically investigate the therapeutic applications of the drug beyond merely preclinical data. Aside from educational reform initiatives, clinicians might proactively launch a platform that integrates telemedicine as well as digital apps, directly linking the patient to the clinician and monitoring the efficacy of program initiatives in real time.
 

References

1. Long A. Consumers’ cannabis buying patterns change markedly in wake of COVID-19 pandemic. Marijuana Business Daily. 2020 Sep 22. https://mjbizdaily.com/consumers-cannabis-buying-patterns-change-markedly-in-wake-of-covid-pandemic/.

2. Bures B. How the coronavirus pandemic is increasing global demand for marijuana. Chicago Tribune. 2020 Jul 1. https://www.chicagotribune.com/marijuana/sns-tft-coronavirus-increases-global-marijuana-demand-20200701-oygaxryb7vhcjfeu44cgacicaa-story.html.

3. Walters J. Marijuana and COVID-19: Top studies. CannaMD. 2020 Aug 19. https://www.cannamd.com/marijuana-covid-19-top-studies/.

4. El Biali M et al. Med Cannabis Cannabinoids. 2020 Aug 19. doi: 10.1159/000510799.

5. LaMotte S. “Smoking weed and coronavirus: Even occasional use raises risk of COVID-19 complications.” CNN Health. 2020 Apr 10. https://www.cnn.com/2020/04/10/health/smoking-weed-coronavirus-wellness/index.html

6. Yafai S and Etengoff S. The case for cannabis: Advising cannabis users about COVID-19. Emergency Medicine News. 2020 May 20;42(5B).

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Mr. Choudhry is a research assistant at the IMCHF. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF and is Mr. Choudhry’s father. Dr. Islam, Mr. Choudhry, and Dr. Choudhry reported no relevant disclosures.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.

The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.^1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.

From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.³ Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.^4,5

Therapeutic strategies that work

“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, American clinicians may need to draw inspiration from international pandemic studies in accordance with evidence-based medicine. Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:

• Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
• Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
• Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).

In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.

Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.

Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).^6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.

Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.

ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.

One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.⁸

 

Toward adopting an integrated model for care

Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.⁹ Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.¹⁰ Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.

ADHD and the self-medication hypothesis

The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).¹¹ Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.

Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
 

References

1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.

2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.

3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.

4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.

5. Ir J Psychol Med. 2020 May 21:1-22.

6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.

7. O’Keefe L. AAP News. 2008 Jun;29(6):1.

8. Asian J Psychiatr. 2020 Jun;51:102077.

9. Current Psychiatry. 2015 Dec;14(12):e3-4.

10. Encephale. 2020 Jun 7;46(3S):S85-92.

11. Current Psychiatry. 2014 Dec; 3(12): e3-4.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.

Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.

The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.^1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.

From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.³ Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.^4,5

Therapeutic strategies that work

“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, American clinicians may need to draw inspiration from international pandemic studies in accordance with evidence-based medicine. Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:

• Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
• Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
• Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).

In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.

Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.

Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).^6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.

Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.

ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.

One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.⁸

 

Toward adopting an integrated model for care

Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.⁹ Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.¹⁰ Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.

ADHD and the self-medication hypothesis

The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).¹¹ Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.

Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
 

References

1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.

2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.

3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.

4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.

5. Ir J Psychol Med. 2020 May 21:1-22.

6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.

7. O’Keefe L. AAP News. 2008 Jun;29(6):1.

8. Asian J Psychiatr. 2020 Jun;51:102077.

9. Current Psychiatry. 2015 Dec;14(12):e3-4.

10. Encephale. 2020 Jun 7;46(3S):S85-92.

11. Current Psychiatry. 2014 Dec; 3(12): e3-4.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.

Recently, the Yakima Health District (YHD), in collaboration with the Washington State Department of Health, issued dramatic revisions to its educational curriculum, opting for exclusively remote learning as an important next step in COVID-19 containment measures.

The newly implemented “enhanced” distance-learning paradigm has garnered considerable national attention. Even more noteworthy is how YHD addressed those with language barriers and learning differences such as ADHD as a “priority group”; these individuals are exempt from the newly implemented measures, and small instructional groups of no more than five “at-risk” students will be directly supervised by specialized educators.^1,2 To overcome these new unprecedented challenges from the coronavirus pandemic, especially from the perspective of distance education and mental health for susceptible groups such as those with ADHD, it is of utmost importance to explore various programs of interest, as well as the targeted therapies being considered during this crisis.

From a therapeutic standpoint, individuals with learning differences are more likely to play catch-up with their age-matched peers. This puts them at significant risk for developmental delays with symptoms manifesting as disruptive behavioral issues. This is why ongoing parental guidance, coupled with a paradoxically stimulating environment, is critical for children and adolescents with ADHD.³ Accumulating evidence, based on a myriad of studies, demonstrates that childhood treatment with ADHD stimulants reduces the incidence of future substance use, as well as that of other negative outcomes.^4,5

Therapeutic strategies that work

“The new normal” has forced unique challenges on clinicians for mitigating distress by novel means of health care delivery. Given the paucity of research exploring the interactions of individuals with ADHD within the context of COVID-19, American clinicians may need to draw inspiration from international pandemic studies in accordance with evidence-based medicine. Take for example, the suggested guidelines from the European ADHD Guidelines Group (EAGG) – such as the following:

• Telecommunications in general, and telepsychiatry in particular, should function as the primary mode of health care delivery to fulfill societal standards of physical distancing.
• Children and adolescents with ADHD should be designated as a “priority group” with respect to monitoring initiatives by educators in a school setting, be it virtual or otherwise.
• Implementation of behavioral strategies by parent or guardian to address psychological well-being and reduce the presence of comorbid behavioral conditions (such as oppositional defiant disorder).

In addition to the aforementioned guidance, EAGG maintains that individuals with ADHD may be initiated on medications after the completion of a baseline examination; if the patients in question are already on a treatment regimen, they should proceed with it as indicated. Interruptions to therapy are not ideal because patients are then subjected to health-related stressors of COVID-19. Reasonable regulations concerning access to medications, without unnecessary delays, undoubtedly will facilitate patient needs, allowing for a smooth transition in day-to-day activities. The family, as a cohesive unit, may benefit from reeducation because it contributes toward the therapeutic process. Neurofeedback, coping skills, and cognitive restructuring training are potential modalities that can augment medications.

Although it may seem counterintuitive, parents or caregivers should resist the urge to increase the medication dose during an outbreak with the intended goal of diminishing the psychosocial burden of ADHD symptomatology. Likewise, unless indicated by a specialist, antipsychotics and/or hypnotics should not be introduced for addressing behavioral dysregulation (such as agitation) during the confinement period.

Historically, numerous clinicians have suggested that patients undergo a routine cardiovascular examination and EKG before being prescribed psychostimulants (the rationale for this recommendation is that sympathomimetics unduly affect blood pressure and heart rate).^6,7 However, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) eventually amended their previous stance by releasing a joint statement in which they deemed a baseline EKG necessary only in ADHD patients with preexisting cardiac risk. For all other patients, the use of EKGs was entirely contingent on physician discretion. However, given the nature of safety precautions for COVID-19, it is prudent to discourage or delay in-person cardiovascular examination/monitoring protocols altogether, especially in those patients without known heart conditions.

Another area of concern is sleep dysfunction, which might exist as an untoward effect of ADHD medication intake or because of the presence of COVID-19 psychosocial stressors. However, clinicians advise that unnecessary psychopharmacology (such as hypnotics or melatonin) be avoided. Instead, conservative lifestyle measures should be enacted, emphasizing the role of proper sleep hygiene in maintaining optimal behavioral health. Despite setbacks to in-person appointments, patients are expected to continue their pharmacotherapy with “parent-focused” ADHD interventions taking a primary role in facilitating compliance through remote monitoring.

ADMiRE, a tertiary-level, dedicated ADHD intervention program from South Dublin, Ireland, has identified several roadblocks with respect to streamlining health care for individuals with ADHD during the confinement period. The proposed resolution to these issues, some of which are derived from EAGG guidelines, might have universal applications elsewhere, thereby facilitating the development of therapeutic services of interest. ADMiRE has noted a correspondence between the guidelines established by EAGG and that of the Canadian ADHD Resource Alliance (CADDRA), including minimal in-person interactions (in favor of virtual teleconferencing) and a cardiovascular screen can be performed in lieu of baseline cardiac auscultation. Moreover, in the event that the patient is a low cardiac risk candidate for ADHD treatment, monitoring protocols may be continued from a home setting. However, if a physical examination is indicated, CADDRA recommends the use of precautionary PPE before commencing ADHD pharmacotherapy.

One of the most significant hurdles is that of school closures because teacher feedback for baseline behavior was traditionally instrumental in dictating patient medical management (for example, for titration schedule). It is expected that, for the time being, this role will be supplanted by parental reports. As well as disclosing information on behavioral dysregulation, family members should be trained to relay critical information about the development of stimulant-induced cardiovascular symptoms – namely, dyspnea, chest pain, and/or palpitations. Furthermore, as primary caregivers, parents should harbor a certain degree of emotional sensitivity because their mood state may influence the child’s overall behavioral course in terms of symptom exacerbation.⁸

 

Toward adopting an integrated model for care

Developing an effective assessment plan for patients with ADHD often proves to be a challenging task for clinicians, perhaps even more so in environments that enforce social distancing and limited physical contact by default. As a neurodevelopmental disorder from childhood, the symptoms (including inattention, hyperactivity, and/or impulsivity) of ADHD do not arise in a vacuum – comorbid conditions include mood and anxiety disorders, which are complicated further by a background risk for substance use and self-medicating tendencies.⁹ Unfortunately, the pandemic has limited the breadth of non-COVID doctors visits, which hinders the overall diagnostic and monitoring process for identifiable comorbid conditions, such as autism spectrum disorder, intellectual disability, oppositional defiant and conduct disorders, and so on.¹⁰ Since ADHD symptoms cannot be treated by pharmacotherapy or behavioral interventions alone, our team advocates that families provide additional emotional support and continuous encouragement during these uncertain times.

ADHD and the self-medication hypothesis

The Khantzian self-medication hypothesis posits that a drug seeker may subconsciously gravitate toward a particular agent only to discover a sense of relief concerning inner turmoil or restlessness after use. Observations support the notion that individuals with undiagnosed ADHD have sought cocaine or even recreational designer drugs (such as methylenedioxypyrovalerone, or “bath salts”).¹¹ Given the similar mechanism of action between cocaine, methylenedioxypyrovalerone, and prescribed psychostimulants such as methylphenidate, the results are hardly surprising because these agents all work on the brain’s “reward center” (for example, the nucleus accumbens) by invoking dopamine release. Aside from the aforementioned self-medication hypothesis, “downers” such as Xanax recently have experienced a prescription spike during the outbreak. While there isn’t an immediate cause for concern of Xanax abuse in ADHD individuals, the potential for addiction is certainly real, especially when taking into account comorbid anxiety disorder or sleep dysfunction.

Because of limited resources and precautionary guidelines, clinicians are at a considerable disadvantage in terms of formulating a comprehensive diagnostic and treatment plan for children and adolescents with ADHD. This situation is further compounded by the recent closure of schools and the lack of feedback with respect to baseline behavior from teachers and specialized educators. This is why it is imperative for primary caregivers to closely monitor children with ADHD for developing changes in behavioral patterns (for example, mood or anxiety issues and drug-seeking or disruptive behavior) and work with health care professionals.
 

References

1. “Distance learning strongly recommended for all Yakima county schools.” NBC Right Now. 2020 Aug 5.

2. Retka J. “Enhanced” remote learning in Yakima county schools? What that means for students this fall. Yakima Herald-Republic. 2020 Aug 8.

3. Armstrong T. “To empower! Not Control! A holistic approach to ADHD.” American Institute for Learning and Development. 1998.

4. J Child Psychol Psychiatry. 2014 Aug;55(8):878-85.

5. Ir J Psychol Med. 2020 May 21:1-22.

6. Lancet Child Adolesc Health. 2020 Jun;4(6):412-4.

7. O’Keefe L. AAP News. 2008 Jun;29(6):1.

8. Asian J Psychiatr. 2020 Jun;51:102077.

9. Current Psychiatry. 2015 Dec;14(12):e3-4.

10. Encephale. 2020 Jun 7;46(3S):S85-92.

11. Current Psychiatry. 2014 Dec; 3(12): e3-4.

Dr. Islam is a medical adviser for the International Maternal and Child Health Foundation (IMCHF), Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Islam disclosed no relevant financial relationships. Zaid Ulhaq Choudhry is a research assistant at the IMCHF. He has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clini-cal research at the IMCHF and is Mr. Choudhry’s father. He has no disclosures.

Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.¹ Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.

As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.² Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants. As clinicians, we must reassess the psychotropic medication regimen for people who are currently being treated for or recovering from COVID-19.
 

What’s at stake for COVID-19–positive mental health care patients?

Although the efficacy of hydroxychloroquine is currently being investigated,³ the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.^3,4

In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues^.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.^5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients⁸ and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.⁹

SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk

Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.

Treatment recommendations

1. Establish a baseline EKG

A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;¹¹ numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.¹²

2. Medical management and risk assessment

Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.

3. Embrace an individually tailored approach to therapeutics

While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,¹² our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
 

References

1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.

2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.

3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.

4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.

5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.

6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.

7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.

8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.

9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.

10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.

11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.

12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
 

Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.

Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.

Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.¹ Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.

As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.² Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants. As clinicians, we must reassess the psychotropic medication regimen for people who are currently being treated for or recovering from COVID-19.
 

What’s at stake for COVID-19–positive mental health care patients?

Although the efficacy of hydroxychloroquine is currently being investigated,³ the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.^3,4

In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues^.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.^5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients⁸ and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.⁹

SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk

Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.

Treatment recommendations

1. Establish a baseline EKG

A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;¹¹ numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.¹²

2. Medical management and risk assessment

Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.

3. Embrace an individually tailored approach to therapeutics

While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,¹² our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
 

References

1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.

2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.

3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.

4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.

5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.

6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.

7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.

8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.

9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.

10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.

11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.

12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
 

Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.

Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.

Over the last few weeks, several conflicting reports about the efficacy of SARS-CoV-2 treatments have emerged, including high-profile papers that were placed in the limelight and groundbreaking retractions that were issued by the Lancet and New England Journal of Medicine, involving the potential dangers of COVID therapy with findings derived from the Surgisphere database. Hydroxychloroquine has garnered considerable media attention and was touted earlier by President Trump for its therapeutic effects.¹ Naturally, there are political connotations associated with the agent, and it is unlikely that hydroxychloroquine will be supplanted in the near future as ongoing clinical trials have demonstrated mixed results amid the controversy.

As clinicians navigating unchartered territory within the hospital setting, we have to come to terms with these new challenges, tailoring treatment protocols accordingly with the best clinical practices in mind. Patients with preexisting mental health conditions and who are being treated for COVID-19 are particularly susceptible to clinical deterioration. Recent studies have indicated that psychiatric patients are more prone to feelings of isolation and/or estrangement as well as exacerbation of symptoms such as paranoia.² Even more concerning is the medication regimen, namely, the novel combination therapies that arise when agents such as hydroxychloroquine are used in tandem with certain antipsychotics or antidepressants. As clinicians, we must reassess the psychotropic medication regimen for people who are currently being treated for or recovering from COVID-19.
 

What’s at stake for COVID-19–positive mental health care patients?

Although the efficacy of hydroxychloroquine is currently being investigated,³ the antimalarial is usually prescribed in tandem with azithromycin for people with COVID-19. The National Institute of Allergy and Infectious Diseases has advised against that particular combination therapy because of ongoing concerns about toxicities.^3,4

In another study, azithromycin was effectively substituted with doxycycline to help minimize systemic effects for patients with cardiac and/or pulmonary issues^.5 Azithromycin is notorious in the literature for influencing the electrical activity of the heart with the potential for fatal arrhythmia and sudden cardiac death in individuals at risk for cardiovascular disease.^5,6,7 It should be noted that both of these commonly prescribed COVID-19 medications (for example, hydroxychloroquine and azithromycin) could lead to QT interval prolongation especially within the context of combination therapy. This is largely concerning for psychiatrists and various other mental health practitioners for the following reasons: (1) higher rates of metabolic syndrome and cardiovascular diseases among psychiatric patients⁸ and/or (2) effects of certain antipsychotics (for example, IV haloperidol, thioridazine, and ziprasidone) and antidepressants (for example, citalopram and escitalopram) on the QT interval.⁹

SARS-CoV-2 and clinical judgment: Evaluating patients at higher risk

Although COVID-19 medication guidelines are still being actively developed, hydroxychloroquine appears to be commonly prescribed by physicians. The medication is known myriad untoward effects, including potential behavioral dysfunction (for example, irritability, agitation, suicidal ideation)10 as well as the aforementioned issues concerning arrhythmia (for example, torsades de pointes). Health care professionals might not have much control over the choice of COVID-19 agents because of a lack of available resources or limited options, but they can exercise clinical judgment with respect to selecting the appropriate psychotropic medications.

Treatment recommendations

1. Establish a baseline EKG

A baseline 12-lead EKG is the standard of care for patients currently being screened for COVID-19. It is necessary to rule out the presence of an underlying cardiovascular disease or a rhythm irregularity. A prolonged QTc interval is generally regarded as being around greater than 450-470 msecs with variations attributable to gender;¹¹ numerous studies have affirmed that the risk of acquiring torsades de pointes is substantial when the QTc interval exceeds 500 msecs.¹²

2. Medical management and risk assessment

Commonly prescribed antipsychotics such as IV haloperidol and ziprasidone are known for exerting a negative effect on the interval and should readily be substituted with other agents in patients who are being treated for COVID-19; the combination of these antipsychotics alongside some COVID-19 medication regimens (for example, hydroxychloroquine/azithromycin) might prove to be fatal. The same logic applies to COVID-19 patients previously on antidepressant therapeutics such as citalopram and escitalopram.

3. Embrace an individually tailored approach to therapeutics

While American Psychiatric Association guidelines historically supported a cessation or reduction in the offending agent under normal circumstances,¹² our team is recommending that the psychotropics associated with QTc interval prolongation are discontinued altogether (or substituted with a low-risk agent) in the event that a patient presents with suspected COVID-19. However, after the patients tests negative with COVID-19, they may resume therapy as indicated under the discretion of the mental health practitioner.
 

References

1. Offard C. “Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients.” The Scientist Magazine. 2020 Jun 4.

2. Shigemura J et al. Psychiatry Clin Neurosci. 2020 Apr;74(4):281-2.

3. Keshtkar-Jahromi M and Bavari S. Am J Trop Med Hyg. 2020 May;102(5):932-3.

4. Palca J. “NIH panel recommends against drug combination promoted by Trump for COVID-19.” NPR. 2020 Apr 21.

5. Mongelli L. “Long Island doctor tries new twist on hydroxychloroquine for elderly COVID-19 patients.” New York Post. 2020 Apr 4.

6. Hancox JC et al. Ther Adv Infect Dis. 2013 Oct;(5):155-65.

7. Giudicessi JR and Ackerman MJ. Cleve Clin J Med. 2013 Sep;80(9):539-44.

8. Casey DE. Am J Med. 2005 Apr 1;118(Suppl 2):15S-22S.

9. Beach SR et al. Psychosomatics. 2013 Jan 1;54(1):1-3.

10. Bogaczewicz A and Sobów T. Psychiatria i Psychologia Kliniczna. 2017;17(2):111-4.

11. Chohan PS et al. Pak J Med Sci. 2015 Sep-Oct;31(5):1269-71.

12. Lieberman JA et al. APA guidance on the use of antipsychotic drugs and cardiac sudden death. NYS Office of Mental Health. 2012.
 

Dr. Faisal A. Islam is medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Faisal Islam disclosed no relevant financial relationships.

Dr. Mohammed Islam is affiliated with the department of psychiatry at the Interfaith Medical Center, New York. He disclosed no relevant financial relationships.

Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. He disclosed no relevant financial relationships.

The N-methyl-D-aspartate (NMDA) antagonist ketamine is a general-purpose anesthetic and Class III controlled substance that has a wide range of clinical applications. In addition to anesthesia, ketamine also is used for analgesia (acute and chronic pain) and critical care due to its receptor properties, which encompass adrenoreceptors, purinergic, opioid, and cholinergic systems.¹ Because it has antidepressant effects, ketamine also is a novel treatment for treatment-resistant depression (TRD).

Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.

Adverse effects of ketamine abuse

Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.² The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.²

While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.³ Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.

At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.⁴ High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.⁵ A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.³

Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.^3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.³ Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.⁶

Treating ketamine abuse

Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.^4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.⁷ Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.⁷

Continue to: Consider referring patients to...

Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.⁸

‘Self-medicating’ ketamine users

Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.

The N-methyl-D-aspartate (NMDA) antagonist ketamine is a general-purpose anesthetic and Class III controlled substance that has a wide range of clinical applications. In addition to anesthesia, ketamine also is used for analgesia (acute and chronic pain) and critical care due to its receptor properties, which encompass adrenoreceptors, purinergic, opioid, and cholinergic systems.¹ Because it has antidepressant effects, ketamine also is a novel treatment for treatment-resistant depression (TRD).

Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.

Adverse effects of ketamine abuse

Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.² The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.²

While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.³ Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.

At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.⁴ High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.⁵ A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.³

Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.^3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.³ Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.⁶

Treating ketamine abuse

Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.^4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.⁷ Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.⁷

Continue to: Consider referring patients to...

Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.⁸

‘Self-medicating’ ketamine users

Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.

The N-methyl-D-aspartate (NMDA) antagonist ketamine is a general-purpose anesthetic and Class III controlled substance that has a wide range of clinical applications. In addition to anesthesia, ketamine also is used for analgesia (acute and chronic pain) and critical care due to its receptor properties, which encompass adrenoreceptors, purinergic, opioid, and cholinergic systems.¹ Because it has antidepressant effects, ketamine also is a novel treatment for treatment-resistant depression (TRD).

Physicians need to be aware, however, that many patients use illicit ketamine, either for recreational purposes or as self-treatment to control depressive symptoms. To help clinicians identify the signs of ketamine abuse, we discuss the adverse effects of illicit use, and suggest treatment approaches.

Adverse effects of ketamine abuse

Ketamine can be consumed in various ways; snorting it in a powder form is a preferred route for recreational use.² The primary disadvantage of oral use is that it increases the likelihood of nausea and vomiting.²

While ketamine is generally safe in a supervised clinical setting, approximately 2.5 million individuals use various illicit forms of ketamine—which is known as Special K and by other names—in recreational settings (eg, dance clubs) where it might be used with other substances.³ Alcohol, in particular, compounds the sedative effects of ketamine and can lead to death by overdose.

At a subanesthetic dose, ketamine can induce dissociative and/or transcendental states that are particularly attractive to those intrigued by mystical experiences, pronounced changes in perception, or euphoria.⁴ High doses of ketamine—relative to a commonly used recreational dose—can produce a unique “K-hole” state in which a user is unable to control his/her body and could lose consciousness.⁵ A K-hole state may trigger a cycle of delirium that warrants immediate clinical attention.³

Researchers have postulated that NMDA antagonism may negatively impact memory consolidation.^3,6 Even more troubling is the potential for systemic injuries because illicit ketamine use may contribute to ulcerative cystitis, severely disturbed kidney function (eg, hydronephrosis), or epigastric pain.³ Chronic abuse tends to result in more systemic sequelae, affecting the bladder, kidneys, and heart. Adverse effects that require emergent care include blood in urine, changes in vision (eg, nystagmus), chest discomfort, labored breathing, agitation, seizures, and/or altered consciousness.⁶

Treating ketamine abuse

Treatment should be tailored to the patient’s symptoms. If the patient presents with “K-bladder” (ie, ketamine bladder syndrome), he/she may need surgical intervention or a cystectomy.^4,7 Therapeutic management of K-bladder entails recognizing bladder symptoms that are specific to ketamine use, such as interstitial or ulcerative cystitis and lower urinary tract symptoms.⁷ Clinicians should monitor patients for increased voiding episodes during the day, voiding urgency, or a general sense of bladder fullness. Patients with K-bladder also may complain of suprapubic pain or blood in the urine.⁷

Continue to: Consider referring patients to...

Consider referring patients to an individualized, ketamine-specific rehabilitation program that is modeled after other substance-specific rehabilitation programs. It is critical to address withdrawal symptoms (eg, anorexia, fatigue, tremors, chills, tachycardia, nightmares, etc.). Patients undergoing ketamine withdrawal may develop anxiety and depression, with or without suicidal ideation, that might persist during a 4- to 5-day withdrawal period.⁸

‘Self-medicating’ ketamine users

Clinicians need to be particularly vigilant for situations in which a patient has used ketamine in an attempt to control his/her depressive symptoms. Some researchers have described ketamine as a revolutionary drug for TRD, and it is reasonable to suspect that some patients with depressive symptoms may have consulted Internet sources to learn how to self-medicate using ketamine. Patients who have consumed smaller doses of ketamine recreationally may have developed a tolerance in which the receptors are no longer responsive to the effects at that dose, and therefore might not respond when given ketamine in a clinical setting. Proper history taking and patient education are essential for these users, and clinicians may need to develop a personalized therapeutic plan for ketamine administration. If, on the other hand, a patient has a history of chronic ketamine use (perhaps at high doses), depression may occur secondary to this type of ketamine abuse. For such patients, clinicians should explore alternative treatment modalities, such as transcranial magnetic stimulation.

Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.¹ Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.

Consider individualized UDS monitoring

The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.² This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.

Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.³ However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.

Additional drug monitoring techniques

Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.^4,5

In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.^6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.⁴

Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.

Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.¹ Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.

Consider individualized UDS monitoring

The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.² This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.

Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.³ However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.

Additional drug monitoring techniques

Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.^4,5

In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.^6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.⁴

Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.

Although urine drug screens (UDS) are most commonly used to screen job applicants, some clinicians have started to use them as a tool for improving their patients’ clinical outcomes.¹ Recently, some clinicians have begun using UDS to help patients who experience chronic pain and dependency (mainly on opioids) and for those who use diverted drugs to relieve these conditions. Many psychiatrists are concerned about the high cost of drug diversion, as well as the possibility of diversion-related patient mortality. Clinicians should therefore consider using UDS as a tool to help address these challenges.

Consider individualized UDS monitoring

The standard 5-substance UDS test panel consists of tetrahydrocannabinol, opiates, amphetamines, cocaine, and phencyclidine. Although this panel was sufficient for an employment screening-related UDS, the American Society of Addiction Medicine (ASAM) has rejected its use for patients with substance abuse. As part of its emphasis on the importance of incorporating preventative procedures, diagnostics, and surveillance protocols, the ASAM advocates using a rotating test panel in conjunction with a patient-specific UDS.² This type of patient-specific regimen would take into account the dynamic nature of a patient’s health profile factors, including comorbid and psychosocial status, subjective pain features, and diverted drug use. Furthermore, the ASAM recommends evaluating patients for the concurrent use of other substances and agents, such as benzodiazepines, sleep-inducing medications, stimulants, and alcohol, because these can interact with opioids.

Consider extending individualized monitoring by implementing standard “cutoff” values for each drug; patients whose levels of a specific substance are above the established cutoff value are categorized as testing positive for the use of that substance. The Substance Abuse Mental Health Services Administration favors adjusting UDS cutoffs, specifically the use of decreased cutoffs, to improve patient compliance.³ However, standardized drug concentration cutoff values may not be applicable for each patient; therefore, such values may need to be carefully tailored to each patient.

Additional drug monitoring techniques

Existing UDS practices, such as medication adherence and compliance, can be supplemented or alternately used with UDS panels that are modified to account for a patient’s fluctuating clinical conditions and concurrent medications. Point-of-care immunoassays, which provide accurate screening for medication compliance and adherence and possible drug diversion, should be used for routine monitoring. Using DNA-authenticated UDS also adds further control in monitoring a patient’s use of different drugs.^4,5

In addition to being helpful for monitoring opioid use, a DNA-verified UDS can be used to evaluate for the presence of synthetic urine substitutes.^6-8 Diversion remains a growing epidemiologic concern, and the number of cases is vastly underreported in the literature. The DNA-authenticated UDS can give clinicians greater precision in identifying synthetic and substituted urine among patient-provided samples.⁴

Using a combination of the methods described here can help expand a clinician’s ability to perform individualized drug monitoring, and verify whether a patient is adhering to his or her treatment regimen.

Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)¹; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.^2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.

How asthma medications work

Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.^3,4

Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to severe asthma.^5,6 Corticosteroids also have been associated with a decrease in serotonin levels, which could contribute to depression.⁷

Possible link between asthma and serotonin

Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.^2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius² emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:

• Persons with asthma presenting with medical symptoms have elevated serotonin levels.
• Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
• Asthma medications have been shown to decrease serotonin levels.^2,3

Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.^2,3

Clinical considerations

Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.

Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)¹; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.^2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.

How asthma medications work

Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.^3,4

Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to severe asthma.^5,6 Corticosteroids also have been associated with a decrease in serotonin levels, which could contribute to depression.⁷

Possible link between asthma and serotonin

Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.^2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius² emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:

• Persons with asthma presenting with medical symptoms have elevated serotonin levels.
• Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
• Asthma medications have been shown to decrease serotonin levels.^2,3

Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.^2,3

Clinical considerations

Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.

Asthma medications comprise several drug classes, including leukotriene antagonists and steroid-based inhalers. These drugs have been implicated in behavioral changes, such as increased hyperactivity, similar to symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)¹; this scenario is more of a concern in children than adults. This raises the question of whether these medications are physiologically linked to behavioral symptoms because of a suggested association with serotonin.^2,3 If this is the case, it is necessary to identify and evaluate possible psychiatric effects of these asthma agents.

How asthma medications work

Some asthma agents, such as montelukast, act as either leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists. These drugs block production of inflammatory leukotrienes, which cause bronchoconstriction. Leukotrienes also can trigger cytokine synthesis, which can modulate leukotriene receptor function. Therefore, leukotriene antagonists could interfere with cytokine function.^3,4

Corticosteroid inhalers suppress inflammatory genes by reversing histone acetylation of inflammatory genes involved in asthma. These inhalers have been shown to reduce cytokine levels in patients with chronic lung disease and those with moderate to severe asthma.^5,6 Corticosteroids also have been associated with a decrease in serotonin levels, which could contribute to depression.⁷

Possible link between asthma and serotonin

Serotonin plays an integral role in observable, dysfunctional behaviors seen in disorders such as ADHD and ODD. In previous studies, serotonin modulated the cytokine network, and patients with asthma had elevated levels of plasma serotonin.^2,3 These findings imply that asthma medications could be involved in altering levels of both cytokines and serotonin. Pretorius² emphasized the importance of monitoring serotonin levels in children who exhibit behavioral dysfunction based on these observations:

• Persons with asthma presenting with medical symptoms have elevated serotonin levels.
• Decreased serotonin levels have been associated with ADHD and ODD; medications for ADHD have been shown to increase serotonin levels.
• Asthma medications have been shown to decrease serotonin levels.^2,3

Asthma medications might be partially responsible for behavioral disturbances, and therapeutic management should integrate the role of serotonin with asthma therapy.^2,3

Clinical considerations

Therapeutic management of asthma should consider psychiatric conditions and treatments. Future research should investigate the overall predisposition for behavioral dysfunction in persons with respiratory syncytial virus, a precursor for asthma. Once an asthma patient’s risk of a psychiatric disorder has been identified, the clinician can determine the most effective medications for treating the condition. If potential medications or genetic or environmental factors are identified, we might expect a move toward personalized care in the not too distant future.