Mental Health

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

This month’s column is driven by the recent increase of youth in crisis, and COVID-19–related limitations of higher-level services. Suicide is the second leading cause of death among youth¹ and populations who face discrimination are at increased risk.^2,3

A pediatrician colleague recently asked me about how to support patients who may be at risk. With inpatient units and emergency departments over capacity, properly allocating resources to patients with the most acute needs is crucial. When appropriate, providing preventive suicide care in primary care similarly saves lives.
 

Case summary

Cassandra is a 16-year-old Black girl who told a friend on Snapchat that she did not want to be alive. The friend told her parents and Cassandra’s parents brought their daughter to an urgent primary care appointment. Cassandra has had a history of difficulty with large transitions like a family move when she was 13. She spent more time in her room for several months before joining the volleyball team and making new friends. She has always done well academically in school but struggled with insomnia and classwork when her high school shifted to remote learning for the 2020-2021 school year because of the pandemic. This year she attends school in person but is unable to play volleyball because of COVID-19 restrictions. Her parents report that she is again spending more time online in her room. She is passing her classes and doing well in math, but overall, her grades have fallen since the pandemic began. She reports recent difficulties with friends and notes feeling hopeless about a changing climate and race relations in the United States.

Discussion

This case example illustrates some factors pediatricians can consider in determining how to proceed in similar circumstances. What are Cassandra’s immediate risk and treatment needs? In cases like Cassandra’s, the American Academy of Pediatrics recommends the ABCD (Assess, Build hope, Connect, Develop a safety plan) approach.⁴ Preparing practices to deliver this best possible preventive suicide care is essential.

1. Is this patient at imminent risk of harming herself?

Assess: Screen for suicide risk and assess risk level. Several standardized screening tools exist for gauging a patient’s risk. The Ask Suicide Screening Questionnaire (asQ) is a straightforward screening tool (not to be confused with the ASQ Ages and Stages developmental screening). These questionnaires take only a few minutes and next steps are suggested depending on the score (low, moderate, or high risk) and clinical judgment. What matters most is using a standardized screener to directly ask questions about suicide and then follow up appropriately based on risk.

2. What can be done during the visit to promote a good outcome?

Build hope/reasons for living. Validate that people sometimes feel suicidal when things are difficult, but that the feelings come and go and people go on to live meaningful lives. Tell the patients that you care about keeping them safe when the feelings come up. Motivational interviewing can be helpful to reflect back patient-identified reasons for living. Genuinely tell the patients how much you care about their wellbeing.

3. What can be done outside the visit to promote a good outcome?

Connect: Strengthen connections with protective adults. Make a plan to have the patient connect regularly with parents/trusted adults. She could engage in social action, or connect one-on-one. With more structured social opportunities, she will spend less time online. Medical practices can reach out with postcards and phone calls to show that they care about the patient, an intervention called “Caring Contacts” that has been shown to decrease suicide.

4. Once suicide risk is identified, what are specific tools to use during the visit to keep her safe?

Develop a plan for staying safe: Restrict access to lethal means, develop a safety plan and healthy ways of coping. There is a free 2-hour CALM (Counseling on Access to Lethal Means) training to help providers feel competent in restricting access to lethal means prior to increased risk. This resource provides safety plan templates that help identify triggers, specific ways to stay safe, people to talk to, and suicide prevention resources including lifelines (988) and chat options (text 2 letter state to 741741).

Enacting suicide prevention requires practice readiness and workflow changes. Providers should assess mental health supports in and out of the office, and then rehearse workflow around suicide prevention care. Increasingly, there are embedded case managers or behavioral health providers available. Sometimes local mental health crisis services are the best option. A practice introductory letter to community mental health practitioners can improve later coordination efforts when caring for suicidal youth. Having practice-level support for provider well-being can improve outcomes.
 

Case follow-up

After interviewing the girl separately, and performing a PHQ-A and an asQ, followed by the Brief Suicide Safety Assessment to screen for acuity, the pediatrician felt confident that Cassandra was suffering from moderate depression and had moderate but not imminent risk of suicide. Options to treat her depression were discussed with Cassandra and her parents, and a referral to therapy was made.

The provider knew that depression care is complementary but not sufficient as standalone suicide prevention. The provider used the asQ pathway to determine next steps. He made a safety plan, and referred her to an outpatient mental health clinician with whom the practice had an established relationship for an urgent mental health evaluation. A follow-up primary care appointment was scheduled within 72 hours to re-check safety and ensure that she had an appointment scheduled to start therapy. A nurse contacted the patient and her family regularly to check on her wellbeing. Her parents made a plan with her volleyball coach to organize outdoor off-season conditioning to help with exercise and socializing. The family removed screens prior to bedtime and sleep improved. At a 3-month follow-up, Cassandra had only mild depressive symptoms and the frequency and intensity of her suicidal ideation had decreased.
 

Dr. Spottswood is a child psychiatrist practicing in an integrated care clinic at the Community Health Centers of Burlington, Vermont, a Federally Qualified Health Center. She is the medical director of the Vermont Child Psychiatry Access Program and a clinical assistant professor in the department of psychiatry at the University of Vermont.
 

References

1. National Institute of Mental Health: Suicide.

2. Hottes TS et al. Am J Public Health. 2016 May;106(5):e1-12.

3. Bridge JA et al. JAMA Pediatr. 2018;172(7):697-9.

4. Asarnow JR. SAMHSA Center for Adolescent Suicide and Self-Harm..

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial show.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was nonsignificant in those with major depressive disorders,” the researchers wrote.

“We assessed for the first time in the same study the effect of ketamine on three a priori–defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, said in an interview.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Dr. Jollant added.  

The study was published online Feb. 2, 2022, in the BMJ.
 

Swift, full remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0-2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Dr. Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs. 32%; odds ratio, 3.7; 95% confidence interval, 1.9-7.3; P < .001).

This antisuicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors reported.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0-92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3-5.2; P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9-17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly versus placebo (69.5% vs. 56.3%; OR, 0.8; 95% CI, 0.3-2.5; P = .7).

The researchers noted the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they wrote.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledged that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They pointed out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.
 

A new perspective on ketamine

In an accompanying editorial, Riccardo De Giorgi, MD, Wellcome Trust doctoral training fellow, department of psychiatry, University of Oxford (England), said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” Dr. De Giorgi wrote.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” Dr. De Giorgi pointed out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” Dr. De Giorgi wrote.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concluded.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Dr. Jollant and Dr. De Giorgi disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.

Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.

On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.

Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.

“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
 

Tennessee data reflect national problem

Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.

Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.

“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
 

How to identify substances, manage overdoses

The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.

They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.

While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.

The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”

Dr. Fuehrlein had no disclosures.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intranasal oxytocin (INOT) is showing early promise as a treatment for cocaine dependence, new research suggests.

Results of a small 6-week randomized, placebo-controlled trial in patients with cocaine use disorder showed a high level of abstinence in those who received INOT beginning 2 weeks after treatment initiation.

“In this population of cocaine-dependent individuals in a community clinic setting, we found the use of intranasal oxytocin to be safe and feasible, with no adverse events, and a high level of abstinence after 6 weeks, compared to placebo,” lead author Wilfrid Noel Raby, PhD, MD, a Teaneck, N.J.–based psychiatrist, said in an interview.

On the other hand, “the findings were paradoxical because there was a greater dropout rate in the intranasal oxytocin group after week 1, suggesting that oxytocin might have a biphasic effect, which should be addressed in future studies,” added Dr. Raby, who was an adjunct clinical professor of psychiatry, division on substance abuse, Montefiore Medical Center, Albert Einstein College of Medicine, New York, when the trial was conducted.

The study was published in the March issue of Drug and Alcohol Dependence Reports.
 

‘Crying need’

“Focus on stress reactivity in addiction and on the loss of social norms among drug users has generated interest in oxytocin, due to its purported role in these traits and regulation of stress,” the authors wrote.

Oxytocin is a neuropeptide that regulates autonomic functions. Previous research in cannabis users suggests it may have a role in treating addiction by reportedly reducing cravings. In addition, earlier research also suggests it cuts stress reactivity and state anger in cocaine users.

A previous trial of INOT showed it decreased cocaine craving, and additional research has revealed recurrent cocaine use results in lower endogenous oxytocin levels and depleted oxytocin in the hypothalamus and amygdala.

“The bias of my work is to look for simple, nonaddictive medicinal approaches that can be used in the community settings, because that’s where the greatest crying need lies and where most problems from drug addiction occur,” said Dr. Raby.

“There has been long-standing interest in how the brain adaptive systems, or so-called ‘stress systems,’ adjust in the face of drug dependence in general, and the main focus of the study has been to understand this response and use the insight from these adaptations to develop medicinal treatments for drug abuse, particularly cocaine dependence,” he added.

To investigate the potential for INOT to promote abstinence from cocaine, the researchers randomized 26 patients with cocaine use disorder (73% male, mean [SD] age, 50.2 [5.4] years). Most participants had been using cocaine on a regular basis for about 25 years, and baseline average days of cocaine use was 11.1 (5.7) during the 30 days prior to study entry.

At a baseline, the researchers collected participants’ medical history and conducted a physical examination, urine toxicology, electrocardiogram, comprehensive metabolic panel, and complete blood count. They used the MINI International Neuropsychiatric Interview to confirm the diagnosis of cocaine dependence.

The study began with a 7-day inpatient abstinence induction stage, after which participants were randomized to receive either INOT 24 IU or intranasal placebo (n = 15 and n = 11, respectively).

Patients attended the clinic three times per week. At each visit, they completed the cocaine craving scale, the Perceived Stress Scale, and the Clinician Global Inventory (all self-reports), as well as the Time Line Follow Back (TLFB) to document cocaine use.

Participants were trained to self-administer an intranasal solution at home, with compliance monitored in two ways – staff observed self-administration of the randomized medication at the time of clinic visits and weighed the “at home bottle.”

Cocaine use was determined via urine toxicology and TLFB self-report.
 

Threshold period

INOT did not induce ≥ 3 weeks of continuous abstinence. However, beginning with week 3, the odds of weekly abstinence increased dramatically in the INOT group, from 4.61 (95% confidence interval,1.05, 20.3) to 15.0 (1.18, 190.2) by week 6 (t = 2.12, P = .037).

The overall medication group by time interaction across all 6 weeks was not significant (F1,69 = 1.73, P = .19); but when the interaction was removed, the difference between the overall effect of medication (INOT vs. placebo) over all 6 weeks “reached trend-level significance” (F1,70) = 3.42, P = .07).

The subjective rating outcomes (cravings, perceived stress, cocaine dependence, and depression) “did not show a significant medication group by time interaction effect,” the authors reported, although stress-induced cravings did tend toward a significant difference between the groups.

Half of the patients did not complete the full 6 weeks. Of those who discontinued, 85% came from the INOT group and 15% from the placebo group. Of the 11 who dropped out from the treatment group, seven were abstinent at the time of discontinuation for ≥ 1 week.

There were no significant differences in rates of reported side effects between the two groups.

“This study highlights some promise that perhaps there is a threshold period of time you need to cross, after which time oxytocin could really be really helpful as acute or maintenance medication,” said Dr. Raby. The short study duration might have been a disadvantage. “We might have seen better results if the study had been 8 or 12 weeks in duration.”

Using motivational approaches during the early phase – e.g., psychotherapy or a voucher system – might increase adherence, and then “after this initial lag, we might see a more therapeutic effect,” he suggested.

Dr. Raby noted that his group studied stress hormone secretions in the cocaine-dependent study participants during the 7-day induction period and that the findings, when published, could shed light on this latency period. “Cocaine dependence creates adaptations in the stress system,” he said.
 

‘Nice first step’

Commenting on the study, Jane Joseph, PhD, professor in the department of neurosciences and director of the neuroimaging division at Medical University of South Carolina, Charleston, said it is “nice to see a clinical trial using oxytocin in cocaine dependence [because] preclinical research has shown fairly convincing effects of oxytocin in reducing craving or stress in the context of cocaine seeking, but findings are rather mixed in human studies.”

Dr. Joseph, who was not involved with the study, said her group’s research showed oxytocin to be the most helpful for men with cocaine use disorder who reported childhood trauma, while for women, oxytocin “seemed to worsen their reactivity to cocaine cues.”

She said the current study is a “nice first step” and suggested that future research should include larger sample sizes to “address some of the individual variability in the response to oxytocin by examining sex differences or trauma history.”

The study was supported by an award from the National Institute of Drug Abuse. Dr. Raby and coauthors and Dr. Joseph have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Updated June 17, 2022

The US Department of Veterans Affairs (VA) provides health care for > 9 million military veterans, nearly half of all former service members.¹ Over the past 15 years, there has been a steady and substantial increase in the frequency of disability awards for veterans with post-9/11 military service. Recent data from the Bureau of Labor Statistics indicate that 41% of veterans who served after 9/11 receive service-connected disability benefits compared with 28% of veterans overall.² More than 5 million veterans receive VA service-related disability benefits.^2,3 More than half of the VA $243 billion budget for fiscal year (FY) 2021 ($135.5 billion) was allocated to the Veterans Benefits Administration (VBA), of which $115.7 billion (85%) was allocated specifically for service-related compensation claims payments.⁴

The VA predicted that VBA will have completed 1.4 million ratings for disability claims in 2021.⁵ A substantial percentage of these claims will be for mental disorders, specifically posttraumatic stress disorder (PTSD). VA officials testifying before Congress in 2017 noted that the number of PTSD claims had nearly tripled in the previous 10 years.⁶ As far back as 2013, McNally and Frueh analyzed “the skyrocketing of disability claims,” particularly for PTSD, among veterans who served in Iraq and Afghanistan.⁷

This large increase has placed an unprecedented burden on the VBA to expand its capacity to conduct initial PTSD disability evaluations that by regulations are completed by psychologists or psychiatrists. This need has led the VBA to make significant changes in the compensation and pension (C&P) process, including a reduced role for Veterans Health Administration (VHA) examiners and increased reliance on non-VA (contract) examiners through the Contract Medical Disability Examination (MDE) program. In 2019, the MDE budget was $1.23 billion; in 2020, it was increased to $1.79 billion, and for 2021, it was $2.23 billion, reflecting the increasing investment of resources in non-VA examiners, ostensibly to both increase capacity and save costs.⁵

Anecdotally, concerns have been raised regarding inadequate training of contract examiners as well as inadequate reports by these examiners. A 2018 Government Accountability Office (GAO) report concluded that VA lacked the data to determine whether contract examiners were meeting standards for quality, timeliness, and accuracy.⁸ The GAO report noted that VA required 92% of contractor reports contained no obvious errors, a relatively low target; however, in the first half of 2017, only 1 contractor group met that target. The report noted further that “VBA does not verify if examiners have completed training nor does it collect information to assess training effectiveness in preparing examiners.”⁸ A subsequent analysis of contract examinations completed by the VA Office of the Inspector General (OIG) in 2019 concluded that the MDE program was “hampered in their ability to provide oversight because of limitations with VBA’s electronic examination management systems, the lack of reliable data, and inadequate staffing of the program.”⁹

These reports have focused almost exclusively on simple performance metrics, such as timeliness of examination completion. However, the 2018 GAO report referenced isolated “focused reviews” of complaints about the quality of examinations by contract examiners and gave as an example an isolated “review of one contracted examiner who had high rates of diagnosing severe posttraumatic stress disorder.”⁸ After review indicated the examiner’s reports were of poor quality, the VBA discontinued the examiner’s contract.

Unfortunately, despite such anecdotal reports and isolated actions, to date there are no published reports examining and comparing the quality of PTSD examination reports completed by VHA and contract examiners or the subsequent disability determinations made by the VBA as a result of these evaluations. In a November 2020 letter to the VA Secretary, 11 US Senators expressed “grave concerns” regarding the VA decision to privatize C&P programs noting, among other concerns, that there were “no clinical quality measurement for, or evaluation of, contractor examinations.”¹⁰ The letter cited anecdotal evidence of contract examiners not reviewing veteran’s medical records and diagnosing conditions “without supporting evidence.”¹⁰

The purpose of the present evaluation was to provide a systematic comparison of the content and quality of initial PTSD disability examinations conducted by VHA and non-VA contract examiners. In addition, this study compared the disability rating decisions resulting from VHA and contract examinations.

Methods

A random sample of 100 Initial PTSD Disability Benefits Questionnaires (DBQs)—structured forms completed by all examiners—were obtained from a list supplied by the VA Office of Performance Analysis and Integrity. All examinations were from the Veterans Integrated Service Network (VISN) 1, encompassing the New England region and were conducted in 2019 and 2020. Two of the 100 cases were excluded for technical reasons, resulting in 98 examination reports. However, the final pool yielded 62 contract examinations and only 36 VHA examinations. To make the sample sizes more comparable, an additional 15 examinations were randomly selected from the local examination database (also VISN 1) to complement the original examination pool.

Once DBQs were retrieved, all identifying information was deleted, and cases were analyzed using assigned record numbers. All coding was completed by the 2 principal investigators, both VA psychologists with extensive training and experience in C&P evaluation and treatment of veterans with PTSD. Due to inherent structural differences between the forms used for VA and contract examinations, raters could not be masked/blinded to the source of the report.

A number of measures were taken to reduce bias and enhance objectivity of rating. First, objectively coded variables (eg, age and sex of veteran, period of service, trauma type, diagnoses rendered by the examiner, impairment category endorsed, number and type of symptoms) were transcribed directly from the DBQ as recorded by the examiner. Second, to rate report quality, an initial categorical rating scale was developed based on predetermined elements of examination quality that were considered essential. After refinement and preliminary analysis of interrater reliabilities, 3 quality-related indices were identified: (1) level of detail in description of key content areas (history before service, service trauma, after service social and vocational history, mental health history, substance use); (2) synthesis of history and findings in explaining opinion rendered; and (3) clarity of opinion regarding causation required “at least as likely as not” degree of confidence. The first 2 quality ratings were based on a 3-point scale (poor, fair, good), and the third variable was coded as yes or no. (eAppendix available at doi:10.12788/fp.0225). Interrater reliabilities calculated based on a subsample of 18 cases, randomly selected and rated by both raters, yielded Cohen κ in the acceptable range (.61, .72, and .89 for detail, synthesis, and clarity, respectively). Finally, for information regarding VBA decision making, rating decision documents contained in the Veterans Benefit Management System database were reviewed to determine whether the veteran was granted service connection for PTSD or another mental disorder based on the examination report in question and, if so, the disability rating percentage awarded. These were recorded independently after all other coding had been completed.

Results

Comparison of VHA and contract examinations revealed no significant differences between groups on relevant sociodemographic and other measures (Table). Missing data were not obtained from other records or sources, and for this study, reflect only what is recorded in the examination reports except for age, which was calculated using veteran’s date of birth and the date of examination.

To examine differences between VHA and contract examinations, the groups were first compared on a set of predetermined objectively coded variables taken directly from the DBQ. The frequency of PTSD diagnoses by VHA (57%) and contract (71%) examiners was not significantly different nor were rates of non-PTSD diagnoses by VHA (51%) and contract (73%) examiners. There also was no difference in the mean number of PTSD symptoms endorsed across PTSD diagnostic criteria B, C, D, and E (maximum of 20) recorded by VHA (9.4) and contract (10.9) examiners.

Contract examiners recorded a significantly greater mean number of “other symptoms” on a checklist of 31 possible symptoms as compared to VHA examiners: 7.3 vs 5.8, respectively (t[104] = 2.27, P < .05). An initial analysis of overall social/vocational impairment ratings coded by examiners did not reveal significant differences between examiner groups. However, when the 2 most severe impairment categories were combined to create a pooled “severe” category, 31% of contract examiners rated veterans as severely impaired compared with only 12% of VHA examiners (χ² = 5.79, 1 df, P < .05) (Figure 1).

Discussion

The present study provides the first reported systematic comparison of VA disability examinations for PTSD completed by examiners employed by the VHA and those hired as contract examiners through the MDE program. Although the frequency of PTSD diagnoses by contract examiners was higher than that of VHA examiners (71% vs 57%, respectively), the difference was not statistically significant. However, contract examiners recorded significantly more symptoms for examinees and rated them as severely impaired more frequently than did their VHA counterparts. In keeping with rating guidelines used by the VBA, these differences in examination content resulted in higher disability ratings for veterans seen by contract examiners.

Along with these elevated reports in symptom and severity ratings, contract examiners were less likely to provide adequate detail in the narrative sections of their reports and less frequently provided a satisfactory explanation and synthesis of relevant history and findings in support of their conclusions. Although not reflected in the statistical analysis, case-by-case review revealed some startlingly inadequate examination reports by contract examiners, several of which contained no review of records, no report or discussion of relevant background, and no discussion or analysis of social and vocational function to inform and support their opinion about level of impairment. None of the VHA examination reports reviewed lacked information to that degree.

Such deficiencies in detail and synthesis run counter to accepted guidelines for the adequate assessment of psychological injury in general and in VA disability claims specifically.^11,12 For example, Watson and colleagues proposed that a minimum of 3 hours was required to conduct an initial PTSD examination, with more complex cases possibly taking longer.¹¹ There is no information available about how long contract examiners take to complete their examinations and how that compares with the time taken by VA examiners. The VBA failure to monitor whether or not examiners follow accepted guidelines for PTSD examination has not previously been evaluated. Historically, a large number of clinicians, researchers, and policy critics have raised concerns about the potential for exaggeration or malingering among VA PTSD disability claimants and have urged the need to adequately assess for unreliable reporting and presentation.^13,14 However, the possibility of systematic examiner deficiency and/or bias increasing the frequency of false or inflated claims being approved has received little empirical attention.

Limitations

A methodological limitation of the present study was that, due to structural differences in the DBQ forms used for VHA and contract examinations, the reports could not be de-identified as to examiner type and thus raters could not be masked/blinded. To mitigate bias, a predetermined, piloted, and refined coding and rating plan for report quality metrics was adhered to strictly, and interrater reliabilities were acceptable. Future study is suggested in which all report content is standardized for coding using the same format, which at present would require a complete rewriting of the entire report; this problem could be resolved by having the VBA adopt a more coherent system in which all reports, regardless of examiner type, use a single, standardized template. Further study using larger data sets and expanding to other VA regions also is needed.

Conclusions

The present study suggests that poor examination and report quality—by contract examiners and to a lesser degree VHA examiners—are not uncommon. The findings confirm and extend previous anecdotal reports of deficiencies in PTSD examinations performed by contract examiners and provide empirical support for concerns raised of global deficiencies in the VBA oversight of the MDE program. Such deficiencies have significant implications for the quality and integrity of the VA disability determination process for veterans claiming PTSD related to military service.

The current findings support and strengthen the call for development and management of a structured and enforced training and quality assurance/improvement program for VA PTSD disability examinations. Such training and oversight will be critical to improve the quality and integrity of these examinations, reduce error and waste in VBA’s Compensation and Pension process, and in doing so optimize VA financial resources to best serve veterans’ benefits and health care needs.

Updated June 17, 2022

The US Department of Veterans Affairs (VA) provides health care for > 9 million military veterans, nearly half of all former service members.¹ Over the past 15 years, there has been a steady and substantial increase in the frequency of disability awards for veterans with post-9/11 military service. Recent data from the Bureau of Labor Statistics indicate that 41% of veterans who served after 9/11 receive service-connected disability benefits compared with 28% of veterans overall.² More than 5 million veterans receive VA service-related disability benefits.^2,3 More than half of the VA $243 billion budget for fiscal year (FY) 2021 ($135.5 billion) was allocated to the Veterans Benefits Administration (VBA), of which $115.7 billion (85%) was allocated specifically for service-related compensation claims payments.⁴

The VA predicted that VBA will have completed 1.4 million ratings for disability claims in 2021.⁵ A substantial percentage of these claims will be for mental disorders, specifically posttraumatic stress disorder (PTSD). VA officials testifying before Congress in 2017 noted that the number of PTSD claims had nearly tripled in the previous 10 years.⁶ As far back as 2013, McNally and Frueh analyzed “the skyrocketing of disability claims,” particularly for PTSD, among veterans who served in Iraq and Afghanistan.⁷

This large increase has placed an unprecedented burden on the VBA to expand its capacity to conduct initial PTSD disability evaluations that by regulations are completed by psychologists or psychiatrists. This need has led the VBA to make significant changes in the compensation and pension (C&P) process, including a reduced role for Veterans Health Administration (VHA) examiners and increased reliance on non-VA (contract) examiners through the Contract Medical Disability Examination (MDE) program. In 2019, the MDE budget was $1.23 billion; in 2020, it was increased to $1.79 billion, and for 2021, it was $2.23 billion, reflecting the increasing investment of resources in non-VA examiners, ostensibly to both increase capacity and save costs.⁵

Anecdotally, concerns have been raised regarding inadequate training of contract examiners as well as inadequate reports by these examiners. A 2018 Government Accountability Office (GAO) report concluded that VA lacked the data to determine whether contract examiners were meeting standards for quality, timeliness, and accuracy.⁸ The GAO report noted that VA required 92% of contractor reports contained no obvious errors, a relatively low target; however, in the first half of 2017, only 1 contractor group met that target. The report noted further that “VBA does not verify if examiners have completed training nor does it collect information to assess training effectiveness in preparing examiners.”⁸ A subsequent analysis of contract examinations completed by the VA Office of the Inspector General (OIG) in 2019 concluded that the MDE program was “hampered in their ability to provide oversight because of limitations with VBA’s electronic examination management systems, the lack of reliable data, and inadequate staffing of the program.”⁹

These reports have focused almost exclusively on simple performance metrics, such as timeliness of examination completion. However, the 2018 GAO report referenced isolated “focused reviews” of complaints about the quality of examinations by contract examiners and gave as an example an isolated “review of one contracted examiner who had high rates of diagnosing severe posttraumatic stress disorder.”⁸ After review indicated the examiner’s reports were of poor quality, the VBA discontinued the examiner’s contract.

Unfortunately, despite such anecdotal reports and isolated actions, to date there are no published reports examining and comparing the quality of PTSD examination reports completed by VHA and contract examiners or the subsequent disability determinations made by the VBA as a result of these evaluations. In a November 2020 letter to the VA Secretary, 11 US Senators expressed “grave concerns” regarding the VA decision to privatize C&P programs noting, among other concerns, that there were “no clinical quality measurement for, or evaluation of, contractor examinations.”¹⁰ The letter cited anecdotal evidence of contract examiners not reviewing veteran’s medical records and diagnosing conditions “without supporting evidence.”¹⁰

The purpose of the present evaluation was to provide a systematic comparison of the content and quality of initial PTSD disability examinations conducted by VHA and non-VA contract examiners. In addition, this study compared the disability rating decisions resulting from VHA and contract examinations.

Methods

A random sample of 100 Initial PTSD Disability Benefits Questionnaires (DBQs)—structured forms completed by all examiners—were obtained from a list supplied by the VA Office of Performance Analysis and Integrity. All examinations were from the Veterans Integrated Service Network (VISN) 1, encompassing the New England region and were conducted in 2019 and 2020. Two of the 100 cases were excluded for technical reasons, resulting in 98 examination reports. However, the final pool yielded 62 contract examinations and only 36 VHA examinations. To make the sample sizes more comparable, an additional 15 examinations were randomly selected from the local examination database (also VISN 1) to complement the original examination pool.

Once DBQs were retrieved, all identifying information was deleted, and cases were analyzed using assigned record numbers. All coding was completed by the 2 principal investigators, both VA psychologists with extensive training and experience in C&P evaluation and treatment of veterans with PTSD. Due to inherent structural differences between the forms used for VA and contract examinations, raters could not be masked/blinded to the source of the report.

A number of measures were taken to reduce bias and enhance objectivity of rating. First, objectively coded variables (eg, age and sex of veteran, period of service, trauma type, diagnoses rendered by the examiner, impairment category endorsed, number and type of symptoms) were transcribed directly from the DBQ as recorded by the examiner. Second, to rate report quality, an initial categorical rating scale was developed based on predetermined elements of examination quality that were considered essential. After refinement and preliminary analysis of interrater reliabilities, 3 quality-related indices were identified: (1) level of detail in description of key content areas (history before service, service trauma, after service social and vocational history, mental health history, substance use); (2) synthesis of history and findings in explaining opinion rendered; and (3) clarity of opinion regarding causation required “at least as likely as not” degree of confidence. The first 2 quality ratings were based on a 3-point scale (poor, fair, good), and the third variable was coded as yes or no. (eAppendix available at doi:10.12788/fp.0225). Interrater reliabilities calculated based on a subsample of 18 cases, randomly selected and rated by both raters, yielded Cohen κ in the acceptable range (.61, .72, and .89 for detail, synthesis, and clarity, respectively). Finally, for information regarding VBA decision making, rating decision documents contained in the Veterans Benefit Management System database were reviewed to determine whether the veteran was granted service connection for PTSD or another mental disorder based on the examination report in question and, if so, the disability rating percentage awarded. These were recorded independently after all other coding had been completed.

Results

Comparison of VHA and contract examinations revealed no significant differences between groups on relevant sociodemographic and other measures (Table). Missing data were not obtained from other records or sources, and for this study, reflect only what is recorded in the examination reports except for age, which was calculated using veteran’s date of birth and the date of examination.

To examine differences between VHA and contract examinations, the groups were first compared on a set of predetermined objectively coded variables taken directly from the DBQ. The frequency of PTSD diagnoses by VHA (57%) and contract (71%) examiners was not significantly different nor were rates of non-PTSD diagnoses by VHA (51%) and contract (73%) examiners. There also was no difference in the mean number of PTSD symptoms endorsed across PTSD diagnostic criteria B, C, D, and E (maximum of 20) recorded by VHA (9.4) and contract (10.9) examiners.

Contract examiners recorded a significantly greater mean number of “other symptoms” on a checklist of 31 possible symptoms as compared to VHA examiners: 7.3 vs 5.8, respectively (t[104] = 2.27, P < .05). An initial analysis of overall social/vocational impairment ratings coded by examiners did not reveal significant differences between examiner groups. However, when the 2 most severe impairment categories were combined to create a pooled “severe” category, 31% of contract examiners rated veterans as severely impaired compared with only 12% of VHA examiners (χ² = 5.79, 1 df, P < .05) (Figure 1).

Discussion

The present study provides the first reported systematic comparison of VA disability examinations for PTSD completed by examiners employed by the VHA and those hired as contract examiners through the MDE program. Although the frequency of PTSD diagnoses by contract examiners was higher than that of VHA examiners (71% vs 57%, respectively), the difference was not statistically significant. However, contract examiners recorded significantly more symptoms for examinees and rated them as severely impaired more frequently than did their VHA counterparts. In keeping with rating guidelines used by the VBA, these differences in examination content resulted in higher disability ratings for veterans seen by contract examiners.

Along with these elevated reports in symptom and severity ratings, contract examiners were less likely to provide adequate detail in the narrative sections of their reports and less frequently provided a satisfactory explanation and synthesis of relevant history and findings in support of their conclusions. Although not reflected in the statistical analysis, case-by-case review revealed some startlingly inadequate examination reports by contract examiners, several of which contained no review of records, no report or discussion of relevant background, and no discussion or analysis of social and vocational function to inform and support their opinion about level of impairment. None of the VHA examination reports reviewed lacked information to that degree.

Such deficiencies in detail and synthesis run counter to accepted guidelines for the adequate assessment of psychological injury in general and in VA disability claims specifically.^11,12 For example, Watson and colleagues proposed that a minimum of 3 hours was required to conduct an initial PTSD examination, with more complex cases possibly taking longer.¹¹ There is no information available about how long contract examiners take to complete their examinations and how that compares with the time taken by VA examiners. The VBA failure to monitor whether or not examiners follow accepted guidelines for PTSD examination has not previously been evaluated. Historically, a large number of clinicians, researchers, and policy critics have raised concerns about the potential for exaggeration or malingering among VA PTSD disability claimants and have urged the need to adequately assess for unreliable reporting and presentation.^13,14 However, the possibility of systematic examiner deficiency and/or bias increasing the frequency of false or inflated claims being approved has received little empirical attention.

Limitations

A methodological limitation of the present study was that, due to structural differences in the DBQ forms used for VHA and contract examinations, the reports could not be de-identified as to examiner type and thus raters could not be masked/blinded. To mitigate bias, a predetermined, piloted, and refined coding and rating plan for report quality metrics was adhered to strictly, and interrater reliabilities were acceptable. Future study is suggested in which all report content is standardized for coding using the same format, which at present would require a complete rewriting of the entire report; this problem could be resolved by having the VBA adopt a more coherent system in which all reports, regardless of examiner type, use a single, standardized template. Further study using larger data sets and expanding to other VA regions also is needed.

Conclusions

The present study suggests that poor examination and report quality—by contract examiners and to a lesser degree VHA examiners—are not uncommon. The findings confirm and extend previous anecdotal reports of deficiencies in PTSD examinations performed by contract examiners and provide empirical support for concerns raised of global deficiencies in the VBA oversight of the MDE program. Such deficiencies have significant implications for the quality and integrity of the VA disability determination process for veterans claiming PTSD related to military service.

The current findings support and strengthen the call for development and management of a structured and enforced training and quality assurance/improvement program for VA PTSD disability examinations. Such training and oversight will be critical to improve the quality and integrity of these examinations, reduce error and waste in VBA’s Compensation and Pension process, and in doing so optimize VA financial resources to best serve veterans’ benefits and health care needs.

Updated June 17, 2022

The US Department of Veterans Affairs (VA) provides health care for > 9 million military veterans, nearly half of all former service members.¹ Over the past 15 years, there has been a steady and substantial increase in the frequency of disability awards for veterans with post-9/11 military service. Recent data from the Bureau of Labor Statistics indicate that 41% of veterans who served after 9/11 receive service-connected disability benefits compared with 28% of veterans overall.² More than 5 million veterans receive VA service-related disability benefits.^2,3 More than half of the VA $243 billion budget for fiscal year (FY) 2021 ($135.5 billion) was allocated to the Veterans Benefits Administration (VBA), of which $115.7 billion (85%) was allocated specifically for service-related compensation claims payments.⁴

The VA predicted that VBA will have completed 1.4 million ratings for disability claims in 2021.⁵ A substantial percentage of these claims will be for mental disorders, specifically posttraumatic stress disorder (PTSD). VA officials testifying before Congress in 2017 noted that the number of PTSD claims had nearly tripled in the previous 10 years.⁶ As far back as 2013, McNally and Frueh analyzed “the skyrocketing of disability claims,” particularly for PTSD, among veterans who served in Iraq and Afghanistan.⁷

This large increase has placed an unprecedented burden on the VBA to expand its capacity to conduct initial PTSD disability evaluations that by regulations are completed by psychologists or psychiatrists. This need has led the VBA to make significant changes in the compensation and pension (C&P) process, including a reduced role for Veterans Health Administration (VHA) examiners and increased reliance on non-VA (contract) examiners through the Contract Medical Disability Examination (MDE) program. In 2019, the MDE budget was $1.23 billion; in 2020, it was increased to $1.79 billion, and for 2021, it was $2.23 billion, reflecting the increasing investment of resources in non-VA examiners, ostensibly to both increase capacity and save costs.⁵

Anecdotally, concerns have been raised regarding inadequate training of contract examiners as well as inadequate reports by these examiners. A 2018 Government Accountability Office (GAO) report concluded that VA lacked the data to determine whether contract examiners were meeting standards for quality, timeliness, and accuracy.⁸ The GAO report noted that VA required 92% of contractor reports contained no obvious errors, a relatively low target; however, in the first half of 2017, only 1 contractor group met that target. The report noted further that “VBA does not verify if examiners have completed training nor does it collect information to assess training effectiveness in preparing examiners.”⁸ A subsequent analysis of contract examinations completed by the VA Office of the Inspector General (OIG) in 2019 concluded that the MDE program was “hampered in their ability to provide oversight because of limitations with VBA’s electronic examination management systems, the lack of reliable data, and inadequate staffing of the program.”⁹

These reports have focused almost exclusively on simple performance metrics, such as timeliness of examination completion. However, the 2018 GAO report referenced isolated “focused reviews” of complaints about the quality of examinations by contract examiners and gave as an example an isolated “review of one contracted examiner who had high rates of diagnosing severe posttraumatic stress disorder.”⁸ After review indicated the examiner’s reports were of poor quality, the VBA discontinued the examiner’s contract.

Unfortunately, despite such anecdotal reports and isolated actions, to date there are no published reports examining and comparing the quality of PTSD examination reports completed by VHA and contract examiners or the subsequent disability determinations made by the VBA as a result of these evaluations. In a November 2020 letter to the VA Secretary, 11 US Senators expressed “grave concerns” regarding the VA decision to privatize C&P programs noting, among other concerns, that there were “no clinical quality measurement for, or evaluation of, contractor examinations.”¹⁰ The letter cited anecdotal evidence of contract examiners not reviewing veteran’s medical records and diagnosing conditions “without supporting evidence.”¹⁰

The purpose of the present evaluation was to provide a systematic comparison of the content and quality of initial PTSD disability examinations conducted by VHA and non-VA contract examiners. In addition, this study compared the disability rating decisions resulting from VHA and contract examinations.

Methods

A random sample of 100 Initial PTSD Disability Benefits Questionnaires (DBQs)—structured forms completed by all examiners—were obtained from a list supplied by the VA Office of Performance Analysis and Integrity. All examinations were from the Veterans Integrated Service Network (VISN) 1, encompassing the New England region and were conducted in 2019 and 2020. Two of the 100 cases were excluded for technical reasons, resulting in 98 examination reports. However, the final pool yielded 62 contract examinations and only 36 VHA examinations. To make the sample sizes more comparable, an additional 15 examinations were randomly selected from the local examination database (also VISN 1) to complement the original examination pool.

Once DBQs were retrieved, all identifying information was deleted, and cases were analyzed using assigned record numbers. All coding was completed by the 2 principal investigators, both VA psychologists with extensive training and experience in C&P evaluation and treatment of veterans with PTSD. Due to inherent structural differences between the forms used for VA and contract examinations, raters could not be masked/blinded to the source of the report.

A number of measures were taken to reduce bias and enhance objectivity of rating. First, objectively coded variables (eg, age and sex of veteran, period of service, trauma type, diagnoses rendered by the examiner, impairment category endorsed, number and type of symptoms) were transcribed directly from the DBQ as recorded by the examiner. Second, to rate report quality, an initial categorical rating scale was developed based on predetermined elements of examination quality that were considered essential. After refinement and preliminary analysis of interrater reliabilities, 3 quality-related indices were identified: (1) level of detail in description of key content areas (history before service, service trauma, after service social and vocational history, mental health history, substance use); (2) synthesis of history and findings in explaining opinion rendered; and (3) clarity of opinion regarding causation required “at least as likely as not” degree of confidence. The first 2 quality ratings were based on a 3-point scale (poor, fair, good), and the third variable was coded as yes or no. (eAppendix available at doi:10.12788/fp.0225). Interrater reliabilities calculated based on a subsample of 18 cases, randomly selected and rated by both raters, yielded Cohen κ in the acceptable range (.61, .72, and .89 for detail, synthesis, and clarity, respectively). Finally, for information regarding VBA decision making, rating decision documents contained in the Veterans Benefit Management System database were reviewed to determine whether the veteran was granted service connection for PTSD or another mental disorder based on the examination report in question and, if so, the disability rating percentage awarded. These were recorded independently after all other coding had been completed.

Results

Comparison of VHA and contract examinations revealed no significant differences between groups on relevant sociodemographic and other measures (Table). Missing data were not obtained from other records or sources, and for this study, reflect only what is recorded in the examination reports except for age, which was calculated using veteran’s date of birth and the date of examination.

To examine differences between VHA and contract examinations, the groups were first compared on a set of predetermined objectively coded variables taken directly from the DBQ. The frequency of PTSD diagnoses by VHA (57%) and contract (71%) examiners was not significantly different nor were rates of non-PTSD diagnoses by VHA (51%) and contract (73%) examiners. There also was no difference in the mean number of PTSD symptoms endorsed across PTSD diagnostic criteria B, C, D, and E (maximum of 20) recorded by VHA (9.4) and contract (10.9) examiners.

Contract examiners recorded a significantly greater mean number of “other symptoms” on a checklist of 31 possible symptoms as compared to VHA examiners: 7.3 vs 5.8, respectively (t[104] = 2.27, P < .05). An initial analysis of overall social/vocational impairment ratings coded by examiners did not reveal significant differences between examiner groups. However, when the 2 most severe impairment categories were combined to create a pooled “severe” category, 31% of contract examiners rated veterans as severely impaired compared with only 12% of VHA examiners (χ² = 5.79, 1 df, P < .05) (Figure 1).

Discussion

The present study provides the first reported systematic comparison of VA disability examinations for PTSD completed by examiners employed by the VHA and those hired as contract examiners through the MDE program. Although the frequency of PTSD diagnoses by contract examiners was higher than that of VHA examiners (71% vs 57%, respectively), the difference was not statistically significant. However, contract examiners recorded significantly more symptoms for examinees and rated them as severely impaired more frequently than did their VHA counterparts. In keeping with rating guidelines used by the VBA, these differences in examination content resulted in higher disability ratings for veterans seen by contract examiners.

Along with these elevated reports in symptom and severity ratings, contract examiners were less likely to provide adequate detail in the narrative sections of their reports and less frequently provided a satisfactory explanation and synthesis of relevant history and findings in support of their conclusions. Although not reflected in the statistical analysis, case-by-case review revealed some startlingly inadequate examination reports by contract examiners, several of which contained no review of records, no report or discussion of relevant background, and no discussion or analysis of social and vocational function to inform and support their opinion about level of impairment. None of the VHA examination reports reviewed lacked information to that degree.

Such deficiencies in detail and synthesis run counter to accepted guidelines for the adequate assessment of psychological injury in general and in VA disability claims specifically.^11,12 For example, Watson and colleagues proposed that a minimum of 3 hours was required to conduct an initial PTSD examination, with more complex cases possibly taking longer.¹¹ There is no information available about how long contract examiners take to complete their examinations and how that compares with the time taken by VA examiners. The VBA failure to monitor whether or not examiners follow accepted guidelines for PTSD examination has not previously been evaluated. Historically, a large number of clinicians, researchers, and policy critics have raised concerns about the potential for exaggeration or malingering among VA PTSD disability claimants and have urged the need to adequately assess for unreliable reporting and presentation.^13,14 However, the possibility of systematic examiner deficiency and/or bias increasing the frequency of false or inflated claims being approved has received little empirical attention.

Limitations

A methodological limitation of the present study was that, due to structural differences in the DBQ forms used for VHA and contract examinations, the reports could not be de-identified as to examiner type and thus raters could not be masked/blinded. To mitigate bias, a predetermined, piloted, and refined coding and rating plan for report quality metrics was adhered to strictly, and interrater reliabilities were acceptable. Future study is suggested in which all report content is standardized for coding using the same format, which at present would require a complete rewriting of the entire report; this problem could be resolved by having the VBA adopt a more coherent system in which all reports, regardless of examiner type, use a single, standardized template. Further study using larger data sets and expanding to other VA regions also is needed.

Conclusions

The present study suggests that poor examination and report quality—by contract examiners and to a lesser degree VHA examiners—are not uncommon. The findings confirm and extend previous anecdotal reports of deficiencies in PTSD examinations performed by contract examiners and provide empirical support for concerns raised of global deficiencies in the VBA oversight of the MDE program. Such deficiencies have significant implications for the quality and integrity of the VA disability determination process for veterans claiming PTSD related to military service.

The current findings support and strengthen the call for development and management of a structured and enforced training and quality assurance/improvement program for VA PTSD disability examinations. Such training and oversight will be critical to improve the quality and integrity of these examinations, reduce error and waste in VBA’s Compensation and Pension process, and in doing so optimize VA financial resources to best serve veterans’ benefits and health care needs.

The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”

The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.

The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:

1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.

2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
 

The study

In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.

The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
 

Results

1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.

2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.

3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
 

Implications

These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.

However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.

These results support the popular notion that stress ages (and sickens) us, and suggest a viable way of minimizing the adverse consequences of stress by strengthening the regulation of emotion and self-control.

In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.

With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.

A version of this article first appeared on Medscape.com.

The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”

The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.

The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:

1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.

2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
 

The study

In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.

The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
 

Results

1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.

2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.

3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
 

Implications

These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.

However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.

These results support the popular notion that stress ages (and sickens) us, and suggest a viable way of minimizing the adverse consequences of stress by strengthening the regulation of emotion and self-control.

In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.

With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.

A version of this article first appeared on Medscape.com.

The increase in cardiovascular disease caused by chronic stress is related to biologic mechanisms (metabolic, hormonal, inflammatory) and to behavioral mechanisms (lifestyle). There is a popular saying that “stress speeds up aging,” which makes sense if we consider the age-old idea that “our age corresponds to that of our arteries.”

The study of the mechanisms of psychosocial risk factors is of major relevance to the creation of the individual and communal preventive strategies that ensure longevity and maintain quality of life.

The following hypotheses were proposed by a group of researchers from Yale University, in New Haven, Conn., in a recent study:

1. Stress is positively associated with accelerated biologic aging, and this relationship will be mediated by stress-related physiologic changes, such as insulin and hypothalamic-pituitary-adrenal (HPA) signaling.

2. Strong factors associated with psychologic resilience will be protective against the negative consequences of stress on aging. (These relationships are predictive, not causative, as this study is cross-sectional.)
 

The study

In their study, the team assessed 444 adults with no chronic medical conditions or psychiatric disorders who were 18-50 years of age and living in the greater New Haven area. Levels of obesity and alcohol consumption in the study cohort were generally in line with those in a community population, so alcohol use and body mass index were used as covariates to account for their impact on the results.

The team also used the latest “epigenetic clock,” known as GrimAge. In recent years, several methods of determining biologic age have been developed that trace chemical changes in the DNA that are natural to the aging process but occur at different moments in different people. The epigenetic clocks have proved to be better predictors of longevity and health than chronologic age, and GrimAge predicts mortality better than other epigenetic clocks.
 

Results

1. Cumulative stress was associated with the acceleration of GrimAge and stress-related physiologic measures of adrenal sensitivity (cortisol/ACTH ratio) and insulin resistance (HOMA). After the researchers controlled for demographic and behavioral factors, HOMA was correlated with GrimAge acceleration.

2. Psychologic resilience factors moderated the association between stress and aging, such that with worse regulation of emotions, there was greater stress-related age acceleration, and with stronger regulation of emotions, any significant effect of stress on GrimAge was prevented. Self-control moderated the relationship between stress and insulin resistance, with high self-control blunting this relationship.

3. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge acceleration, even when demographic, physiologic, and behavioral covariates were accounted for.
 

Implications

These results elegantly demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

Even after adjustment for demographic and behavioral factors – such as smoking, body mass index, race, and income – people with high chronic stress scores showed markers of accelerated aging and physiologic changes, such as increased insulin resistance.

However, individuals with high scores on two psychologic resilience measures – emotion regulation and self-control – were more resilient to the effects of stress on aging and insulin resistance.

These results support the popular notion that stress ages (and sickens) us, and suggest a viable way of minimizing the adverse consequences of stress by strengthening the regulation of emotion and self-control.

In other words, the greater the psychologic resilience, the more likely the individual is to live a long and healthy life. “We like to feel as if we have some sovereignty over our destiny and, therefore, it is worth emphasizing to people (and healthcare providers) that it is important to invest in mental health,” said one of the study researchers.

With all the stress we face these days, it is essential to remember that there is no health without mental health. Above all, if we can achieve greater psychologic resilience, we will have a better chance of delaying aging.

A version of this article first appeared on Medscape.com.

In the United States, mortality rates are high and increasing among working-age adults, and “deaths of despair” from suicide, alcohol poisoning, and drug overdose are key contributors.

This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.

One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.

In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.

The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
 

U.S. is an outlier

From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.

However, much of modern life offers few opportunities for surprise and dopamine pulses.

“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.

The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.

The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.

Modern life is more isolating, often with hours spent alone in front of a computer screen.

Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.

So why has the United States suffered more deaths of despair?

Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.

This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.

By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.

However, they caution against the “medicalization” of every identified cause of rising death rates.

“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.

“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.

Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the United States, mortality rates are high and increasing among working-age adults, and “deaths of despair” from suicide, alcohol poisoning, and drug overdose are key contributors.

This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.

One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.

In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.

The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
 

U.S. is an outlier

From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.

However, much of modern life offers few opportunities for surprise and dopamine pulses.

“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.

The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.

The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.

Modern life is more isolating, often with hours spent alone in front of a computer screen.

Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.

So why has the United States suffered more deaths of despair?

Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.

This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.

By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.

However, they caution against the “medicalization” of every identified cause of rising death rates.

“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.

“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.

Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the United States, mortality rates are high and increasing among working-age adults, and “deaths of despair” from suicide, alcohol poisoning, and drug overdose are key contributors.

This is not the case in 16 other industrialized nations, however, including Canada, Australia, and Japan, where mortality rates are actually decreasing.

One likely reason is that other countries take better care of their citizens from cradle to grave, authors Peter Sterling, PhD, and Michael Platt, PhD, of the University of Pennsylvania, Philadelphia, wrote in a special communication in JAMA Psychiatry published online Feb. 2.

In the United States, individuals and families often struggle in isolation to navigate the life cycle, whereas other countries offer communal assistance to every life stage, and this support protects individuals and families in the long term, they noted.

The United States could solve this “health crisis” by adopting the best practices of these other nations, they wrote.
 

U.S. is an outlier

From an anthropological perspective, Dr. Sterling and Dr. Platt point out that “hunter-gatherers” prioritized food, comfort, and companionship. When one of these needs is unexpectedly met, the surprise triggers a pulse of the feel-good hormone dopamine.

However, much of modern life offers few opportunities for surprise and dopamine pulses.

“It is the difference between a day’s hard walk to finally encounter and kill a wild pig to feed the family and community versus a quick trip to aisle 7 to select a pork roast in plastic wrap,” Dr. Sterling and Dr. Platt noted.

The hunter-gatherers were far more physically active, and cardiovascular disease, diabetes, obesity, and hypertension were virtually unknown.

The small-scale societies of hunters and gatherers depended on strong family bonds and cooperation with community members.

Modern life is more isolating, often with hours spent alone in front of a computer screen.

Yet the lack of natural dopamine producers in modern society and the increased social isolation is not unique to the United States but holds across the board for industrialized nations.

So why has the United States suffered more deaths of despair?

Dr. Sterling and Dr. Platt assert that it comes down to public support other countries provide their citizens across the life span, from prenatal care and quality preschool and elementary school to affordable (or free) education beyond high school.

This support did not require “bloody revolutions, just simple agreements to prepay basic human needs from public funds collected as taxes,” Dr. Sterling and Dr. Platt noted.

By adopting some of the best practices pioneered by other wealthy nations, the United States could reduce despair and restore to many the will to live, they added.

However, they caution against the “medicalization” of every identified cause of rising death rates.

“Every symptom of despair has been defined as a disorder or dysregulation within the individual. This incorrectly frames the problem, forcing individuals to grapple on their own,” they wrote.

“It also emphasizes treatment by pharmacology, providing innumerable drugs for anxiety, depression, anger, psychosis, and obesity, plus new drugs to treat addictions to the old drugs. We cannot defeat despair solely with pills – to the contrary, pills will only deepen it,” they added.

Dr. Platt reported receiving grant support from the National Institutes of Health, the National Science Foundation, and the Charles E. Kaufman Foundation. He is cofounder of Cogwear and a scientific adviser to Neuroflow, Amplio, Blue Horizon International, and Progenity. Dr. Sterling has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

An otherwise healthy 55-year-old male, with no previous psychiatric or medical history, sought care with a family medicine physician for the first time in decades.

Medical symptoms began Oct. 9, 2021, with “some leg weakness and mild sniffles.” Since he was going to be at a public event, he decided to take a PCR test for the SARS-CoV-2 virus on Oct. 13. The patient tested positive.

His symptoms continued to worsen, and he experienced severe body fatigue, sleep disturbance, and lethargy. “A few days after my positive test, the cognitive and physical symptoms dramatically ramped up,” the patient recalled.

Because of those worsening symptoms, on Oct. 20, the patient obtained a new patient appointment with a family medicine physician. After a telemedicine evaluation, the family medicine physician began a multifaceted early outpatient COVID-19 treatment protocol,¹ as I (C.M.W.) and colleagues wrote about late last year. However, this treatment began late in the course because of the patient’s initial resistance to seek care.

This early outpatient treatment protocol for COVID-19 included vitamin D3 125 mcg (5,000 ICU), N-acetylcysteine (NAC) 600 mg every day x 30 days; acetylsalicylic acid 325 mg every day x 30 days; azithromycin 250 mg b.i.d. before every meal x 10 days; hydroxychloroquine sulfate 200 mg b.i.d. x 10 days; ivermectin 3 mg, 5 pills daily x 10 days; zinc sulfate 220 mg (50 mg elemental) every day x 30 days; and a prednisone taper (30 mg daily x 3 days, tapering down 5 mg every 3 days). Hydroxyzine 50 mg at bedtime as needed was added for sleep. The patient did not comment to the family physician on any of the psychological or psychiatric symptoms and responded appropriately to questions during the Oct. 20 initial evaluation.

However, he later described that around the time the PCR was positive, “COVID twisted my brain. I could not think straight. Every thought required 50 times the effort.” For example, he was watching a simple YouTube video for work and “everything was confusing me ... it rattled me, and I couldn’t understand it.” He described his COVID-19 mind as: “The words in my head would come out in a jumbled order, like the message from the words in my brain to my mouth would get crossed. I had trouble spelling and texting. Total cognitive breakdown. I couldn’t do simple mathematics.”

Despite his physical exhaustion, he endured a 3-day period of sleep deprivation. During this time, he recalled looking up at the roof and thinking, “I need to jump off the roof” or thinking, “I might want to throw myself under a bus.” He did not initially reveal his suicidal thoughts to his family medicine physician. After beginning COVID-19 treatment, the patient had two nights of sleep and felt notably improved, and his physical symptoms began to remit. However, the sleeplessness quickly returned “with a vengeance” along with “silly suicidal thoughts.” The thoughts took on a more obsessional quality. For example, he repeatedly thought of jumping out of his second-story bedroom to the living room below and was preoccupied by continually looking at people’s roofs and thinking about jumping. Those thoughts intensified and culminated in his “going missing,” leading his wife to call the police. It was discovered that he had driven to a local bridge and was contemplating jumping off.

After that “going missing” incident, the patient and his wife reached out to their family medicine physician. He reevaluated the patient and, given the new information about the psychiatric symptoms, strongly recommended stat crisis and psychiatric consultation. After discussing the case on the same day, both the family medicine physician and the psychiatrist recommended stat hospital emergency department (ED) assessment on Oct. 29. In the ED, a head CT without contrast at the recommendation of both psychiatrist and family physician, routine electrolytes, CBC with differential, and EKG all were within normal limits. The ED initially discharged him home after crisis evaluation, deciding he was not an imminent risk to himself or others.

The next day, the psychiatrist spoke on the phone with the patient, family medicine physician, and the patient’s wife to arrange an initial assessment. At that time, it remained unclear to all whether the obsessional thoughts had resolved to such a degree that the patient could resist acting upon them. Further, the patient’s sleep architecture had not returned to normal. All agreed another emergency ED assessment was indicated. Ultimately, after voluntary re-evaluation and a difficult hold in the crisis unit, the patient was admitted for psychiatric hospitalization on Oct. 29 and discharged on Nov. 4.

In the psychiatric hospital, venlafaxine XR was started and titrated to 75 mg. The patient was discovered to be hypertensive, and hydrochlorothiazide was started. The discharge diagnosis was major depressive disorder, single episode, severe, without psychotic features.
 

Posthospitalization course

The patient’s clinical course cleared remarkably. He was seen for his initial psychiatric outpatient assessment postpsychiatric hospitalization on Nov. 9, as he had not yet been formally evaluated by the psychiatrist because of the emergency situation.

Gabapentin 300 mg by mouth at bedtime was started, and his sleep architecture was restored. The initial plan to titrate venlafaxine XR into dual selective norepinephrine reuptake inhibitor dose range was terminated, and his psychiatrist considered tapering and discontinuing the venlafaxine XR. A clinical examination, additional history, and collateral data no longer necessarily pointed to an active major depressive disorder or even unspecified depressive disorder, though to be sure, the patient was taking 75 mg of venlafaxine XR. While there were seasonal stressors, historically, nothing had risen to the level of MDD.

The obsessions driving his thoughts to jump off buildings and bridges had completely remitted. His cognitive ability returned to baseline with an ability to focus and perform the complicated tasks of his high-intensity work by the Dec. 8 psychiatric examination, where he was accompanied by his wife. He described feeling like, “I snapped back to like I was before this crazy stuff happened.” His mood was reported as, “Very good; like my old self” and this was confirmed by his wife. His affect was calmer and less tense. He was now using gabapentin sparingly for sleep. We continued to entertain discontinuing the venlafaxine XR, considering this recent severe episode likely driven by the COVID-19 virus. The decision was made to continue venlafaxine XR through the winter rather than discontinuing, remaining on the conservative side of treatment. The patient’s diagnosis was changed from “MDD, single episode,” to “mood disorder due to known physiologic condition (COVID-19) (F06.31) with depressive features; resolving.” At the patient’s follow-up examination on Jan. 5, 2022, he was continuing to do well, stating, “The whole series of crazy events happened to someone else.” The hydrochlorothiazide had been discontinued, and the patient’s blood pressure and pulse were normal at 119/81 and 69, respectively. He had made strategic changes at work to lessen stressors during the typically difficult months.
 

Discussion

Literature has discussed neuropsychiatric sequelae of COVID-19.² The cited example questions whether psychiatric symptoms are tied directly to the viral infection or to the “host’s immune response.” We believe our case represents a direct neurocognitive/neuropsychiatric insult due to the COVID-19 infection.

This case presents a 55-year-old male with no previous psychiatric or medical history with new onset significant and debilitating cognitive impairment and obsessive thoughts of throwing himself from his bedroom balcony ending up at a bridge struggling with an irrational thought of jumping; ultimately requiring psychiatric hospitalization for acute suicidal thoughts. The patient’s psychiatric symptoms arose prior to any and all medication treatment. The obsessive thoughts correlated both with the onset of SARS-CoV-2 infection and a period of sleep deprivation subsequent to the infection. A course of steroid treatment and taper were started after the onset of neurocognitive-psychiatric symptoms, though there is close timing. We submit that the patient experienced, as part of the initial neurocognitive psychiatric initiating cascade, a COVID-19–induced sleep deprivation that was not etiologic but part of the process; since, even when sleep returned to normal, it was still several weeks before full cognitive function returned to baseline.

An argument could be made for possible MDD or unspecified depressive disorder, as historically there had been work-related stressors for the patient at this time of year because of the chronological nature of his work; though previously nothing presented with obsessional suicidal thinking and nothing with any cognitive impairment – let alone to this incapacitating degree.

The patient describes his seasonal work much like an accountant’s work at the beginning of each year. In the patient’s case, the months of September and October are historically “nonstop, working days,” which then slow down in the winter months for a period of recuperation. In gathering his past history of symptoms, he denied neurovegetative symptoms to meet full diagnostic criteria for MDD or unspecified depressive disorder, absent this episode in the presence of SARS-CoV-2 infection.

We could also consider a contributory negative “organic push” by the viral load and prednisone helping to express an underlying unspecified depression or MDD, but for the profound and unusual presentation. There was little prodrome of depressive symptoms (again, he reported his “typical” extraordinary work burden for this time of year, which is common in his industry).

In this patient, the symptoms have remitted completely. However, the patient is currently taking venlafaxine XR 75 mg. We have considered tapering and discontinuing the venlafaxine – since it is not entirely clear that he needs to be on this medication – so this question remains an open one. We did decide, however, to continue the venlafaxine until after the winter months and to reassess at that time.
 

Conclusion

The patient presented with new onset psychological and psychiatric symptoms in addition to physiologic symptoms; the former symptoms were not revealed prior to initial family medicine evaluation. As the symptoms worsened, he and his wife sought additional consultation with family physician, psychiatrists, and ED. Steroid treatment may have played a part in exacerbation of symptoms, but the neuropsychiatric cognitive symptoms were present prior to initiation of all pharmacologic and medical treatment. The successful outcome of this case was based upon quick action and collaboration between the family medicine physician, the psychiatrist, and the ED physician. The value of communication, assessment, and action via phone call and text cannot be overstated. Future considerations include further large-scale evaluation of multifaceted early treatment of patients with COVID-19 within the first 72 hours of symptoms to prevent not only hospitalization, morbidity, and mortality, but newly recognized psychological and psychiatric syndromes.^3,4

Lastly, fluvoxamine might have been a better choice for adjunctive early treatment of COVID-19.⁵ As a matter of distinction, if a lingering mood disorder or obsessive-compulsive disorder remain a result of SARS-CoV-2 or if one were to start an antidepressant during the course of illness, it would be reasonable to consider fluvoxamine as a potential first-line agent.

Dr. Kohanski is a fellowship trained forensic psychiatrist and a diplomate of the American Board of Psychiatry & Neurology. She maintains a private practice in Somerset, N.J., and is a frequent media commentator and medical podcaster. Dr. Kohanski has no conflicts of interest. Dr. Wax is a residency-trained osteopathic family medicine physician in independent private practice in Mullica Hill, N.J. He has authored multiple papers over 2 decades on topics such as SARS-CoV-2 and COVID-19 early treatment. He has been a speaker and media host over 2 decades and served on the National Physicians Council on Healthcare Policy’s congressional subcommittee. Dr. Wax has no conflicts of interest.

References

1. Rev Cardiovasc Med. 2020 Dec 30;21(4):517-30.

2. Brain Behav Immun. 2020 Jul;87:34-9.

3. Trav Med Infect Dis. 2020 May-Jun 35;10738.

4. Kirsch S. “Early treatment for COVID is key to better outcomes.” Times of India. 2021 May 21.

5. Lancet. 2022 Jan 1;10(1):E42-E51.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Four decades into the AIDS epidemic and for some, it’s as if gains in awareness, advances in prevention and treatment, and the concept of undetected equals untransmissable (U=U) never happened. In its place, people living with HIV continue to face discrimination and stigma that affect nearly every aspect of the care continuum, from testing, prevention, and treatment to linkage to sexual, health, and reproductive services.

Accordingly, findings from a Harris poll conducted Oct. 13-18, 2021, among 5,047 adults (18 and older) residing in Australia, Portugal, the United Kingdom, and the United States, reveal that 88% of those surveyed believe that negative perceptions toward people living with HIV persist even though HIV infection can be effectively managed with antiretroviral therapy (ART). Conversely, three-quarters (76%) are unaware of U=U, and the fact that someone with HIV who is taking effective treatment cannot pass it on to their partner. Two-thirds incorrectly believe that a person living with HIV can pass it onto their baby, even when they are ART adherent.

“The survey made me think of people who work in HIV clinics, and how much of a bubble I think that we in the HIV field live in,” Nneka Nwokolo, MBBS, senior global medical director at ViiV Healthcare, London, and practicing consultant in sexual health and HIV medicine, told this news organization. “I think that we generally feel that everyone knows as much as we do or feels the way that we do.”
 

Misconceptions abound across the globe

The online survey, which was commissioned by ViiV Healthcare, also highlights that one in five adults do not know that anyone can acquire HIV regardless of lifestyle, thereby perpetuating the stereotype that HIV is a disease that only affects certain populations, such as men who have sex with men (MSM) or transgender women (TGW). 

Pervasive stereotypes and stigmatization only serve to magnify preexisting social inequities that affect access to appropriate care. A recent editorial published in the journal AIDS and Behavior underscores that stigma experienced by marginalized populations in particular (for example, Black MSM, TGW) is directly linked to decreased access to and use of effective HIV prevention and treatment services. Additionally, once stigma becomes internalized, it might further affect overall well-being, mental health, and social support.

“One of the most significant consequences of the ongoing stigma is that people are scared to test and then they end up coming to services late [when] they’re really ill,” explained Dr. Nwokolo. “It goes back to the early days when HIV was a death sentence ... it’s still there. I have one patient who to this day hates the fact that he has HIV, that he has to come to the clinic – it’s a reminder of why he hates himself.”

Great strides in testing and advances in treatment might be helping to reframe HIV as a chronic but treatable and preventable disease. Nevertheless, survey findings also revealed that nearly three out of five adults incorrectly believe that a person living with HIV will have a shorter lifespan than someone who is HIV negative, even if they are on effective treatment. 

These beliefs are especially true among Dr. Nwokolo’s patient base, most of whom are Africans who’ve immigrated to the United Kingdom from countries that have been devastated by the HIV epidemic. “Those who’ve never tested are reluctant to do so because they are afraid that they will have the same outcome as the people that they know that they’ve left behind,” she said.
 

HIV stigma in the era of 90-90-90

While there has been progress toward achieving UN AID’s 90-90-90 targets (that is, 90% living with HIV know their status, 90% who know their status are on ART, and 90% of people on ART are virally suppressed), exclusion and isolation – the key hallmarks of stigma – may ultimately be the most important barriers preventing a lofty goal to end the AIDS epidemic by the year 2030.

“Here we are, 40 years in and we are still facing such ignorance, some stigma,” Carl Schmid, MBA, former cochair of the Presidential Advisory Council on HIV/AIDS, and executive director of HIV+Policy Institute, told this news organization. “It’s gotten better, but it is really putting a damper on people being tested, getting treated, getting access to PrEP.” Mr. Schmid was not involved in the Harris Poll.

Mr. Schmid also said that, in addition to broader outreach and education as well as dissemination of information about HIV and AIDS from the White House and other government leaders, physician involvement is essential. 

“They’re the ones that need to step up. They have to talk about sex with their patients, [but] they don’t do that, especially in the South among certain populations,” he noted.

Data support the unique challenges faced by at-risk individuals living in the southern United States. Not only do Southern states account for roughly half of all new HIV cases annually, but Black MSM and Black women account for the majority of new diagnoses, according to the Centers for Disease Control and Prevention. Data have also demonstrated discrimination and prejudice toward people with HIV persist among many medical professionals in the South (especially those working in rural areas).

But this is not only a Southern problem; a 2018 review of studies in clinicians across the United States published in AIDS Patient Care and STDs linked provider fear of acquiring HIV through occupational exposure to reduced quality of care, refusal of care, and anxiety, especially among providers with limited awareness of PrEP. Discordant attitudes around making a priority to address HIV-related stigma versus other health care needs also reduced overall care delivery and patient experience.

“I think that the first thing that we as HIV clinicians can and should do – and is definitely within our power to do – is to educate our peers about HIV,” Dr. Nwokolo said, “HIV has gone off the radar, but it’s still out there.”

The study was commissioned by Viiv Healthcare. Dr. Nwokolo is an employee of ViiV Healthcare. Mr. Schmid disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A spoonful of sugar helps the medicine go down – but what if the sugar is the medicine?

Nearly three in four children with irritable bowel syndrome (IBS) or unexplained abdominal pain reported at least a 30% improvement in discomfort after taking a regimen of sugar water they knew had no medicinal properties.

The findings, published online in JAMA Pediatrics on Jan. 31, 2022, also revealed that participants used significantly less rescue medications when taking the so-called “open-label placebo.” The magnitude of the effect was enough to meet one of the criteria from the Food and Drug Administration to approve drugs to treat IBS, which affects between 10% and 15% of U.S. children.

Although open-label placebo is not ready for clinical use, IBS expert Miranda van Tilburg, PhD, said she is “glad we have evidence” of a strong response in this patient population and that the results “may make clinicians rethink how they introduce treatments.

“By emphasizing their belief that a treatment may work, clinicians can harness the placebo effect,” Dr. van Tilburg, professor of medicine and vice chair of research at Marshall University, Huntington, W.Va., told this news organization.

Study leader Samuel Nurko, MD, MPH, the director of the functional abdominal pain program at Harvard Medical School, Boston, said placebo-controlled trials in patients with IBS and functional abdominal pain consistently show a “very high placebo response.” The question his group set out to answer, he said, was: “Can we get the pain symptoms of these children better by giving them placebo with no deception?”

Between 2015 and 2018, Dr. Nurko and colleagues randomly assigned 30 children and adolescents, aged 8-18 years, with IBS or functional abdominal pain to receive either an open-label inert liquid placebo – consisting of 85% sucrose, citric acid, purified water, and the preservative methyl paraben – twice daily for 3 weeks followed by 3 weeks with no placebo, or to follow the reverse sequence. Roughly half (53%) of the children had functional abdominal pain, and 47% had IBS as defined by Rome III criteria.

Researchers at the three participating clinical sites followed a standardized protocol for explaining the nature of placebo (“like sugar pills without medication”), telling participants that adults with conditions like theirs often benefit from placebo when they receive it as part of blinded, randomized clinical trials. Participants in the study were allowed to use hyoscyamine, an anticholinergic medication, as rescue treatment during the trial.

Dr. Nurko’s team reported that patients had a mean pain score of 39.9 on a 100-point visual analogue scale during the open-label placebo phase of the trial and a mean score of 45 during the control period. That difference was statistically significant (P = .03).

Participants took an average of two hyoscyamine pills during the placebo phase, compared with 3.8 pills during the 3-week period when they did not receive placebo (P < .001).

Nearly three-fourths (73.3%) of children in the study reported that open-label placebo improved their pain by over 30%, thus meeting one of the FDA’s criteria for clinical evaluation of drugs for IBS. Half said the placebo liquid cut their pain by more than 50%.

Dr. Nurko said the findings highlight the need to address “mind-body connections” in the management of gut-brain disorders. Like Dr. van Tilburg, he cautioned that open-label placebo “is not ready for widespread use. Placebo is complicated, and we need to understand the mechanism” underlying its efficacy.

“The idea is eventually we will be able to sort out the exact mechanism and harness it for clinical practice,” he added.

However, Dr. van Tilburg expressed that using placebo therapy to treat children and adolescents with these conditions could send the message that “the pain is not real or all in their heads. Children with chronic pain encounter a lot of stigma, and this kind of treatment may increase the feeling of not being believed. We should be careful to avoid this.”

The study was funded by the National Institutes of Health, the Swiss National Science Foundation, the Schwartz family fund, the Foundation for the Science of the Therapeutic Relationship, and the Morgan Family Foundation.

A version of this article first appeared on Medscape.com.

A spoonful of sugar helps the medicine go down – but what if the sugar is the medicine?

Nearly three in four children with irritable bowel syndrome (IBS) or unexplained abdominal pain reported at least a 30% improvement in discomfort after taking a regimen of sugar water they knew had no medicinal properties.

The findings, published online in JAMA Pediatrics on Jan. 31, 2022, also revealed that participants used significantly less rescue medications when taking the so-called “open-label placebo.” The magnitude of the effect was enough to meet one of the criteria from the Food and Drug Administration to approve drugs to treat IBS, which affects between 10% and 15% of U.S. children.

Although open-label placebo is not ready for clinical use, IBS expert Miranda van Tilburg, PhD, said she is “glad we have evidence” of a strong response in this patient population and that the results “may make clinicians rethink how they introduce treatments.

“By emphasizing their belief that a treatment may work, clinicians can harness the placebo effect,” Dr. van Tilburg, professor of medicine and vice chair of research at Marshall University, Huntington, W.Va., told this news organization.

Study leader Samuel Nurko, MD, MPH, the director of the functional abdominal pain program at Harvard Medical School, Boston, said placebo-controlled trials in patients with IBS and functional abdominal pain consistently show a “very high placebo response.” The question his group set out to answer, he said, was: “Can we get the pain symptoms of these children better by giving them placebo with no deception?”

Between 2015 and 2018, Dr. Nurko and colleagues randomly assigned 30 children and adolescents, aged 8-18 years, with IBS or functional abdominal pain to receive either an open-label inert liquid placebo – consisting of 85% sucrose, citric acid, purified water, and the preservative methyl paraben – twice daily for 3 weeks followed by 3 weeks with no placebo, or to follow the reverse sequence. Roughly half (53%) of the children had functional abdominal pain, and 47% had IBS as defined by Rome III criteria.

Researchers at the three participating clinical sites followed a standardized protocol for explaining the nature of placebo (“like sugar pills without medication”), telling participants that adults with conditions like theirs often benefit from placebo when they receive it as part of blinded, randomized clinical trials. Participants in the study were allowed to use hyoscyamine, an anticholinergic medication, as rescue treatment during the trial.

Dr. Nurko’s team reported that patients had a mean pain score of 39.9 on a 100-point visual analogue scale during the open-label placebo phase of the trial and a mean score of 45 during the control period. That difference was statistically significant (P = .03).

Participants took an average of two hyoscyamine pills during the placebo phase, compared with 3.8 pills during the 3-week period when they did not receive placebo (P < .001).

Nearly three-fourths (73.3%) of children in the study reported that open-label placebo improved their pain by over 30%, thus meeting one of the FDA’s criteria for clinical evaluation of drugs for IBS. Half said the placebo liquid cut their pain by more than 50%.

Dr. Nurko said the findings highlight the need to address “mind-body connections” in the management of gut-brain disorders. Like Dr. van Tilburg, he cautioned that open-label placebo “is not ready for widespread use. Placebo is complicated, and we need to understand the mechanism” underlying its efficacy.

“The idea is eventually we will be able to sort out the exact mechanism and harness it for clinical practice,” he added.

However, Dr. van Tilburg expressed that using placebo therapy to treat children and adolescents with these conditions could send the message that “the pain is not real or all in their heads. Children with chronic pain encounter a lot of stigma, and this kind of treatment may increase the feeling of not being believed. We should be careful to avoid this.”

The study was funded by the National Institutes of Health, the Swiss National Science Foundation, the Schwartz family fund, the Foundation for the Science of the Therapeutic Relationship, and the Morgan Family Foundation.

A version of this article first appeared on Medscape.com.

A spoonful of sugar helps the medicine go down – but what if the sugar is the medicine?

Nearly three in four children with irritable bowel syndrome (IBS) or unexplained abdominal pain reported at least a 30% improvement in discomfort after taking a regimen of sugar water they knew had no medicinal properties.

The findings, published online in JAMA Pediatrics on Jan. 31, 2022, also revealed that participants used significantly less rescue medications when taking the so-called “open-label placebo.” The magnitude of the effect was enough to meet one of the criteria from the Food and Drug Administration to approve drugs to treat IBS, which affects between 10% and 15% of U.S. children.

Although open-label placebo is not ready for clinical use, IBS expert Miranda van Tilburg, PhD, said she is “glad we have evidence” of a strong response in this patient population and that the results “may make clinicians rethink how they introduce treatments.

“By emphasizing their belief that a treatment may work, clinicians can harness the placebo effect,” Dr. van Tilburg, professor of medicine and vice chair of research at Marshall University, Huntington, W.Va., told this news organization.

Study leader Samuel Nurko, MD, MPH, the director of the functional abdominal pain program at Harvard Medical School, Boston, said placebo-controlled trials in patients with IBS and functional abdominal pain consistently show a “very high placebo response.” The question his group set out to answer, he said, was: “Can we get the pain symptoms of these children better by giving them placebo with no deception?”

Between 2015 and 2018, Dr. Nurko and colleagues randomly assigned 30 children and adolescents, aged 8-18 years, with IBS or functional abdominal pain to receive either an open-label inert liquid placebo – consisting of 85% sucrose, citric acid, purified water, and the preservative methyl paraben – twice daily for 3 weeks followed by 3 weeks with no placebo, or to follow the reverse sequence. Roughly half (53%) of the children had functional abdominal pain, and 47% had IBS as defined by Rome III criteria.

Researchers at the three participating clinical sites followed a standardized protocol for explaining the nature of placebo (“like sugar pills without medication”), telling participants that adults with conditions like theirs often benefit from placebo when they receive it as part of blinded, randomized clinical trials. Participants in the study were allowed to use hyoscyamine, an anticholinergic medication, as rescue treatment during the trial.

Dr. Nurko’s team reported that patients had a mean pain score of 39.9 on a 100-point visual analogue scale during the open-label placebo phase of the trial and a mean score of 45 during the control period. That difference was statistically significant (P = .03).

Participants took an average of two hyoscyamine pills during the placebo phase, compared with 3.8 pills during the 3-week period when they did not receive placebo (P < .001).

Nearly three-fourths (73.3%) of children in the study reported that open-label placebo improved their pain by over 30%, thus meeting one of the FDA’s criteria for clinical evaluation of drugs for IBS. Half said the placebo liquid cut their pain by more than 50%.

Dr. Nurko said the findings highlight the need to address “mind-body connections” in the management of gut-brain disorders. Like Dr. van Tilburg, he cautioned that open-label placebo “is not ready for widespread use. Placebo is complicated, and we need to understand the mechanism” underlying its efficacy.

“The idea is eventually we will be able to sort out the exact mechanism and harness it for clinical practice,” he added.

However, Dr. van Tilburg expressed that using placebo therapy to treat children and adolescents with these conditions could send the message that “the pain is not real or all in their heads. Children with chronic pain encounter a lot of stigma, and this kind of treatment may increase the feeling of not being believed. We should be careful to avoid this.”

The study was funded by the National Institutes of Health, the Swiss National Science Foundation, the Schwartz family fund, the Foundation for the Science of the Therapeutic Relationship, and the Morgan Family Foundation.

A version of this article first appeared on Medscape.com.