Mental Health

Depression or an anxiety disorder in male adolescents was associated with a 20% increased likelihood of experiencing an acute MI in midlife in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.

The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.

Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.

The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.

In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.

Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”

She reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Bergh C et al. ESC 2020, Abstract 90524.

Depression or an anxiety disorder in male adolescents was associated with a 20% increased likelihood of experiencing an acute MI in midlife in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.

The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.

Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.

The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.

In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.

Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”

She reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Bergh C et al. ESC 2020, Abstract 90524.

Depression or an anxiety disorder in male adolescents was associated with a 20% increased likelihood of experiencing an acute MI in midlife in a Swedish national registry study presented at the virtual annual congress of the European Society of Cardiology.

The association was mediated in part by poor stress resilience and lack of physical fitness among these teenagers with an affective disorder, reported Cecilia Bergh, PhD, of Obrero (Sweden) University.

Her study was made possible by Sweden’s comprehensive national health care registries coupled with the Nordic nation’s compulsory conscription for military service. The mandatory conscription evaluation during the study years included a semistructured interview with a psychologist to assess stress resilience through questions about coping with everyday life, a medical history and physical examination, and a cardiovascular fitness test using a bicycle ergometer.

The study included 238,013 males born in 1952-1956. They were aged 18-19 years when they underwent their conscription examination, at which time 34,503 of them either received or already had a diagnosis of depression or anxiety. During follow-up from 1987 to 2010, a first acute MI occurred in 5,891 of the men. The risk was increased 51% among those with an earlier teen diagnosis of depression or anxiety.

In a Cox regression analysis adjusted for levels of adolescent cardiovascular risk factors, including blood pressure, body mass index, and systemic inflammation, as well as additional potential confounders, such as cognitive function, parental socioeconomic index, and a summary disease score, the midlife MI risk associated with adolescent depression or anxiety was attenuated, but still significant, with a 24% increase. Upon further statistical adjustment incorporating adolescent stress resilience and cardiovascular fitness, the increased risk of acute MI in midlife associated with adolescent depression or anxiety was further attenuated yet remained significant, at 18%.

Dr. Bergh shared her thoughts on preventing this increased risk of acute MI at a relatively young age: “Effective prevention might focus on behavior, lifestyle, and psychosocial stress in early life. If a healthy lifestyle is encouraged as early as possible in childhood and adolescence, it is more likely to persist into adulthood and to improve longterm health. So look for signs of stress, depression, or anxiety that is beyond normal teenager behavior and a persistent problem. Teenagers with poor well-being could benefit from additional support to encourage exercise and also to develop strategies to deal with stress.”

She reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Bergh C et al. ESC 2020, Abstract 90524.

Serotonin, or 5-hydroxytryptamine (5-HT), is a chemical neurotransmitter in the central and peripheral nervous systems that was discovered in 1940s. ¹ O ne of the most widely studied chemical messengers , serotonin influences many physiologic functions in humans, including regulation of mood, sleep-wake cycle, appetite suppression, memory, emesis, breathing, cognition, blood coagulation, libido, and many other functions. ² In 1992, Insel and colleagues first document ed the toxic symptoms produced from too much serotonin in the central and peripheral nervous systems , naming it serotonin syndrome. ^3,4

Serotonin Syndrome

Experts in the fields of psychiatry, pharmacy, and toxicology refer to these symptoms as serotonin toxicity, because the symptoms result from the toxic effects of too much serotonin.^5-9 The term toxicity instead of syndrome “clarifies that it is a form of poisoning, just as lithium toxicity is a form of poisoning.”⁶ Therefore, serotonin toxicity (ST) can develop with administration of any serotonin-enhancing medication, including therapeutic use, polypharmacy, or accidental/intentional drug overdose.

The incidence of ST has increased over the past decade.^5,6,10,11 Several reasons explain this increase: (1) ST mirrors the increase in depression in the US populations^10,12,13; (2) There has been an increase in off-label antidepressant prescribing by both primary care and mental health providers^14-16; (3) the increased use of illicit drugs¹³; (4) an increase in suicide attempts with antidepressants¹⁷; and (5) increased use of opioids for pain management, including both prescription and illicit use.^11,14 This paper reviews the potential lethal combinations of commonly prescribed medications used to treat both veteran and nonveteran patients and includes the latest information on offending medications; a presentation of symptoms from in utero to adult; diagnostic criteria; and recommended treatments.

The Veterans Health Administration (VHA) and non-VHA health care providers can play a key role in identifying and preventing serotonin syndrome/ST by keeping abreast of the latest updates of potentially lethal drug combinations. Commonly prescribed medications with the potential for a reaction include antidepressants, anxiolytics, pain medications, antinausea medications, herbal medications, and over-the-counter (OTC) medications, such as cough suppressants. Patients may be at increased risk for ST due to the growth of polypharmacy management of comorbidities.

Antidepressants

Over the past decade, antidepressant use has increased substantially in the US,United Kingdom, and Canada.¹⁴ Also the types of antidepressants prescribed has changed and been replaced with the newer agents. The selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have replaced the older tricyclics (TCAs) and monoamine oxidase inhibitors (MAOIs) as first-line treatments for depression due to their improved comparative efficacy, reduced mortality following overdose, adverse effects (AEs) that are more tolerable for most patients, and the SSRIs have no anticholinergic properties (except paroxetine) (Table 1).¹⁸

In 2017 the National Institute of Mental Health reported that about 17 million adults and 3 million adolescents (aged 11-18 years) experienced at least 1 episode of major depression.¹⁹ About 40% of US veterans will experience depression, which is 3 times higher than the rate of the general US population.¹² A random sampling survey conducted of about 17,000 active-duty service members by the US Department of Defense (DoD) from November 2015 to April 2016 revealed 9.4% reported depression.²⁰ Antidepressant usage in the US and among veterans continues to increase.^12,16 In 2018, the list of top US prescribed drugs, included sertraline (14th), citalopram (21st), trazodone (24th), and escitalopram (26th).²¹ Antidepressant prescribing in the US increased 18% from 2012 to 2017.²² This trend also continues within the military with a 40% increase of antidepressant use in the past decade.¹⁶

One reason for the increase in antidepressant use is off-label prescribing.^14,23 A sampling of about 2 billion psychiatric outpatient visits in a western portion of the US found 12.9% of the prescriptions filled were off-label.¹⁵ In Minnesota, off-label prescribing of antidepressants was found to contribute to an increase in drug interactions in elderly nursing home residents.²⁴ An investigation by the Military Times of the military community revealed off-label prescribing occurs not only with antidepressant medications, but also with anticonvulsants, antipsychotics, anti-anxiety drugs, and antiepileptic medications.¹⁴

A case report that brought ST to the forefront occurred in the 1980s and involved a college student.²⁵ She was initially diagnosed with the flu. Her symptoms progressed over a 24-hour period despite treatment, leading to seizures, hyperthermia, generalized clonus, muscle rigidity, respiratory failure, and death because of unrecognized ST. Her combination of serotonin-elevating drugs included meperidine, phenelzine, chlorpheniramine, and haldol. On autopsy, there were traces of cocaine found in some of her tissue samples.

Pathophysiology

Tryptophan is a precursor of serotonin and must be ingested from foods, including meats, dairy, fruits, and seeds. About 90% of all serotonin is made in the gastrointestinal epithelium and is the major component of the brain-gut axis.²⁶ Serotonin cannot cross the blood-brain barrier; therefore, it is synthesized and stored in presynaptic terminals around the midline of the brainstem.^1,26 Transport of serotonin is provided by serotonin transporter (SERT).^1,26,27 Once released, serotonin can either stimulate postsynaptic neuron receptors or is taken up into the presynaptic terminals for reuse. SSRI antidepressants, such as citalopram and paroxetine inhibit the reuptake of serotonin by binding to 2 different sites on the SERT thus allowing more available serotonin to be accessible to other neurons.²⁷ There are 7 families of serotonin receptors, 5-HT1 to 5-HT7 and at least 15 mammalian subtypes.^28,29 The majority of these receptors have been implicated in depression or depressive-like behavior as evidenced by the efficacy of increasing extracellular serotonin for the treatment of depression with SSRIs, SNRIs, TCAs, and MAOIs.²⁹ Three of the most studied receptors include 5-HT_IA,5-HT_1B,and 5-HT_2A.

Etiology

Most serotonin-induced drug fatalities occur when combining serotonergic drugs that work through different pathways (Table 2).³⁰ The most toxic combination of serotonin-enhancing drugs includes MAOIs taken with SSRIs or SNRIs, or a combination of 2 MAOIs.^5-9

Other potentially lethal combinations may includepolypharmacy with antidepressants, pain medications, OTC medications, and illicit drugs. Linezolid, a new synthetic antimicrobial, is considered to be a weak MAOI. Therefore, prescribing it with other serotonin-elevating agents has been reported to precipitate ST.¹⁸

Most cases of ST do not require hospitalization and can be managed by stopping the medication or decreasing the dose. Therapeutic doses of a single drug are highly unlikely to cause toxicity, although there have been reported cases of patients who are sensitive or more susceptible and develop symptoms after administration of a single agent and/or a dosage increase.

Delayed ST reactions have occurred because of a prolonged half-life of a drug, iron deficiency anemia, and coingestion of shorter acting serotonin antagonists.³¹ Most antidepressants have a short half-life (< 24 hours)except for fluoxetine. A decrease in iron may contribute to ST because iron is needed to process serotonin from tryptophan. An example of 2 shorter-acting serotonin antagonists include cyproheptadine and olanzapine. Cyproheptadine is used in the treatment of ST, and olanzapine is an antipsychotic.

Symptoms

Symptoms of ST range from mild to severe and include a combination of neuromuscular, autonomic, and mental status changes (Table 3).^5,10 Mild symptoms of ST can start within 1 to 2 hours after ingesting a medication that increases serotonin to a toxic state unless the drug has a long half-life (eg, fluoxetine). Sometimes mild symptoms of ST can be difficult to distinguish from common drug AEs, flu symptoms, or viruses. Patients taking therapeutic doses of SSRIs can experience serotonin symptoms, such as lower limb hyperreflexia or a few beats of ankle clonus without being toxic. One thing to remember is that not all patients will start with mild symptoms and may present in moderate or severe distress.

Moderate-to-severe ST symptoms require hospitalization, usually in the intensive care unit (ICU). At this stage, clonus progresses from the lower extremities to the upper body and becomes more generalized. Ocular clonus can be continuous, intermittent, or have a ping pong effect (short cycle, periodic, alternating lateral gaze).

Severe ST is life threatening and leads to multiorgan failure within hours if not treated. The patient is intubated to assist with breathing and sedated because excess agitation and muscular tremors can increase temperature, which is already elevated by the time the symptoms reach the severe state. Of note, hyperthermia is due to a noninfectious elevation of body temperature from hypertonicity, agitation, and muscle rigidity.A true core temperature > 105.8°F causes irreversible cell damage, cerebral injury, and death.^32,33 The patient can develop seizures and a coma. Multiorgan failure occurs, including rhabdomyolysis, myoglobinuria, renal failure, metabolic acidosis, acute respiratory distress, and disseminated intravascular coagulation.

Diagnosis

The diagnosis of ST is clinical and based on a history of ingesting serotonin-elevating medications and physical findings as per Hunter Serotonin Toxicity Criteria³⁴ (Table 4). An in-depth history needs to include previous and current prescriptions, indications of the prescriptions (eg, therapeutic, increase in dosage, suicide intent), OTC medications, and illicit drug use. Early recognition of symptoms, identification of serotonergic medications, and appropriate resuscitative measures lead to more successful outcomes. A serotonin drug level is ineffective and does not correlate with the dosage since serotonin does not cross the blood-brain barrier.

The type of drug determines the length and response of the episode. The drug(s) elimination half-lives need to be calculated along with the pharmacokinetic or pharmacodynamics; agonist, antagonist, reuptake inhibitor, etc. Many drugs have half-lives of < 24 hours; therefore, reducing or eliminating the offending drug(s) will result in a steady reduction of symptoms.Exceptions include medications with a longer activity, such as the irreversible MAOIs (eg, phenelzine, isocarboxazid) and drugs with a longer half-life, such as fluoxetine. These types of medications may have been stopped weeks earlier and may prolong reduction of symptoms.

When initiating or increasing SSRIs or SNRIs, there are common nontoxic AEs that are not consistent with ST, including anxiety, restlessness, and irritability that may last for 2 weeks. The difference in toxic vs nontoxic reactions are the timing and rapid progression of symptoms. The toxic symptoms will start within hours of ingesting the offending agents(s) and progress rapidly to severe symptoms within 24 hours. Therefore, it is imperative to review AEs with the patient and or caregiver, so they may act as their own advocate and seek immediate assistance.

Differentials

There are symptoms specific to ST that can be used to differentiate it from other conditions. These include hyperthermia, bilateral symmetric clonus (inducible, spontaneous, ocular), and hyperreflexia.These criteria form the basis for Hunter criteria.

Differential diagnoses to consider include neuroleptic malignant syndrome; antidepressant initiation AEs; antidepressant discontinuation syndrome; malignant hyperthermia; anticholinergic toxicity; meningitis/encephalitis; sepsis; drug overdose; alcohol/benzodiazepine withdrawal; and preeclampsia. Neuroleptic malignant syndrome (NMS) is the disorder most often misdiagnosed as ST.Key elements that distinguish ST from NMS include the timing of the clinical course (NMS develops over days to weeks); the medications ingested (NMS from dopaminergic drugs); and the symptoms of NMS (bradyreflexia, bradykinesia, bradyphrenia, and no clonus).According to Gillman, serotonin toxicity is a manifestation of toxicity that is predictable and common with specific drug combinations, while NMS is a “rare idiosyncratic reaction to essentially normal doses and very rarely occurs after overdoses.”³⁵ Preeclampsia is a pregnancy complication that can mimic ST with symptoms of hypertension, clonus, and hyperreflexia. It has been estimated to complicate 2% to 8% of pregnancies and remains a principle cause of maternal and fetal morbidity and mortality.^36,37

Treatment

Mild-to-moderate symptoms usually resolve on their own 1 to 3 days after decreasing or stopping the offending drug. The timing will depend on the half-life or active metabolites of the drug. Treatment is largely supportive and may require treatment for control of agitation with benzodiazepines and IV fluids for dehydration/hypotension.¹⁴ In cases not responding to supportive care, treatment with oral cyproheptadine is recommended.¹⁴

There are other medications that have been used in treatment such as olanzapine, chlorpromazine, propranolol, bromocriptine, dantrolene, droperidol, and haloperidol, but their efficacy is unproven and not recommended.¹⁰ Chlorpromazine can cause hypotension and increase hyperthermia. Propranolol has a long duration of action, may cause a prolonged hypotension, and can mask tachycardia that can be used to monitor the effectiveness of treatment.¹⁰ Bromocriptine is a serotonin agonist and may exacerbate symptoms. Dantrolene has no effect on survival in animal models.¹⁰ Droperidol and haloperidol can worsen hyperthermia by inhibiting sweating.³⁸

Mechanical ventilation should be considered especially if muscle rigidity progresses and depressed respiratory function occurs. If the temperature starts to rise, immediate sedation, paralysis, mechanical ventilation, and cyproheptadine are administered.The overall goal is prevention of hyperthermia, which leads to multiorgan failure. A core temperature of ≥ 104°F is associated with neurologic cell death, and recovery is minimal.³² Consultation with an experienced toxicologist is strongly recommended.Antipyretics should not be used, because elevated temperature is centrally mediated from muscle rigidity. If presentation occurs within 1 hour, activated charcoal can be used for detoxification of potentially lethal amounts.

Warning Label Controversies

In 2006, the US Food and Drug Administration (FDA) issued an advisory warning against concurrently using a tryptan antimigraine drug and serotonin-mediated medications.³⁹ In 2018, a research team conducted a 14-year retrospective analysis on 20,000 patients who were coprescribed a tryptan drug with SSRIs or SNRIs.⁴⁰ The study reported that the risk of ST was rare and suggested that the FDA reconsider their advisory. There are several other controversial medications with a ST FDA warning label due to their mechanisms of action and inaccurate case reports.⁴¹

Human Poisonings

Consistent with the 2017 American Association of Poison Control Centers Toxic Exposure report, antidepressants continue to be in the top 5 substance classes most frequently involved in human exposures.⁴² Most accidental ingestions of antidepressants occur in toddlers, whereas intentional ingestions are usually done by adolesents.⁴³ Over the past 10 years, antidepressants are the No. 1 fastest growing category of human exposures in all age groups.⁴²

ST in the Pediatric Population

ST in the pediatric population mirrors that in adults.Differences include the inability of the child to report symptoms, lack of clinician awareness, and reluctance of adolescents to disclose recreational drug use.Management is the same as for adults, including discontinuing the offending drug, supportive care, adequate sedation, oxygen, IV fluids, and continuous cardiac monitoring. Sedation is weight based for benzodiazepines. Mild-to-moderate reactions require admission for observation. Severe reactions require admission to the ICU.

There have been at least 4 published case reports of children aged < 6 years with moderate-to-severe ST secondary to acute vilazodone ingestion.⁴⁴ The dosages included 5.5 to 37 mg/kg. All 4 patients had altered mental status, seizures, hyperthermia, mild clonus, tachycardia, and hypertension. They all survived with intensive care treatment, including intubation, sedation, cyproheptadine in 2 cases, activated charcoal and IV lorazepam in the other cases.

Direk and colleagues reported a case of a 12-year-old girl who was brought to the emergency department by her stepmother for seizurelike activity and was diagnosed with epilepsy and status epilepticus.⁴⁵ In the pediatric ICU she developed tachycardia, fever, agitation, dilated pupils, tremors, increased deep tendon reflexes, spontaneous clonus, and horizontal ocular movements. A detailed clinical history was retaken and revealed that the child had been prescribed risperidone 1 week before by the psychiatric clinic due to behavioral problems, including stealing money, lying, and running away from home and school. On further investigation, the stepmother was taking clomipramine and discovered 9 missing pills.

Pregnancy and Lactation

The American College of Obstetricians and Gynecologists recommends that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms, using a standardized, validated tool and complete a full assessment of mood and emotional well-being during the postpartum, including screening for postpartum depression and anxiety with a validated instrument.⁴⁶ Treatment with antidepressants is controversial. “Current evidence is generally reassuring and indicates that the absolute risks of negative infant outcomes are small except for PNAS [poor neonatal adaptation syndrome], which largely appears to be self-limited.”⁴⁷ Antidepressants cross the human placenta and fetal blood-brain barrier.⁴⁸ Several cases of infant toxicity from SSRIs have been reported with citalopram and escitalopram.^49,50 Symptoms included severe muscle rigidity, lethargy, tachycardia, QTc prolongation, altered consciousness, hypertonia, and seizures at birth. These mothers had taken an SSRI during pregnancy.

Conclusions

This article highlights some of the latest information on ST. Increased awareness of all clinicians and their patients may help decrease unnecessary comorbidities and death. Early identification of ST symptoms will increase the chances for survival, because of the rapid progression of symptoms within 24 hours. Most fatal reactions occur when combining MAOIs with SSRIs, SNRIs, or another MAOI. Overdose with an SSRI does not progress to the severe symptoms unless combined with another serotonin-elevating medication.

Education of all patients who are prescribed antidepressants must include awareness of the potential for serotonergic drug interactions, particularly from OTC medications, herbal medications, and illicit drugs. The diagnosis of ST is based on clinical findings and there must be a history of ingesting serotonin-elevating drug(s). Hunter Serotonin Toxicity Criteria is the gold standard for diagnosing symptoms along with consulting a toxicologist. Prevention of ST includes informed clinicians, patient education, careful prescribing and monitoring, and avoidance of multidrug regimens.

Serotonin, or 5-hydroxytryptamine (5-HT), is a chemical neurotransmitter in the central and peripheral nervous systems that was discovered in 1940s. ¹ O ne of the most widely studied chemical messengers , serotonin influences many physiologic functions in humans, including regulation of mood, sleep-wake cycle, appetite suppression, memory, emesis, breathing, cognition, blood coagulation, libido, and many other functions. ² In 1992, Insel and colleagues first document ed the toxic symptoms produced from too much serotonin in the central and peripheral nervous systems , naming it serotonin syndrome. ^3,4

Serotonin Syndrome

Experts in the fields of psychiatry, pharmacy, and toxicology refer to these symptoms as serotonin toxicity, because the symptoms result from the toxic effects of too much serotonin.^5-9 The term toxicity instead of syndrome “clarifies that it is a form of poisoning, just as lithium toxicity is a form of poisoning.”⁶ Therefore, serotonin toxicity (ST) can develop with administration of any serotonin-enhancing medication, including therapeutic use, polypharmacy, or accidental/intentional drug overdose.

The incidence of ST has increased over the past decade.^5,6,10,11 Several reasons explain this increase: (1) ST mirrors the increase in depression in the US populations^10,12,13; (2) There has been an increase in off-label antidepressant prescribing by both primary care and mental health providers^14-16; (3) the increased use of illicit drugs¹³; (4) an increase in suicide attempts with antidepressants¹⁷; and (5) increased use of opioids for pain management, including both prescription and illicit use.^11,14 This paper reviews the potential lethal combinations of commonly prescribed medications used to treat both veteran and nonveteran patients and includes the latest information on offending medications; a presentation of symptoms from in utero to adult; diagnostic criteria; and recommended treatments.

The Veterans Health Administration (VHA) and non-VHA health care providers can play a key role in identifying and preventing serotonin syndrome/ST by keeping abreast of the latest updates of potentially lethal drug combinations. Commonly prescribed medications with the potential for a reaction include antidepressants, anxiolytics, pain medications, antinausea medications, herbal medications, and over-the-counter (OTC) medications, such as cough suppressants. Patients may be at increased risk for ST due to the growth of polypharmacy management of comorbidities.

Antidepressants

Over the past decade, antidepressant use has increased substantially in the US,United Kingdom, and Canada.¹⁴ Also the types of antidepressants prescribed has changed and been replaced with the newer agents. The selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have replaced the older tricyclics (TCAs) and monoamine oxidase inhibitors (MAOIs) as first-line treatments for depression due to their improved comparative efficacy, reduced mortality following overdose, adverse effects (AEs) that are more tolerable for most patients, and the SSRIs have no anticholinergic properties (except paroxetine) (Table 1).¹⁸

In 2017 the National Institute of Mental Health reported that about 17 million adults and 3 million adolescents (aged 11-18 years) experienced at least 1 episode of major depression.¹⁹ About 40% of US veterans will experience depression, which is 3 times higher than the rate of the general US population.¹² A random sampling survey conducted of about 17,000 active-duty service members by the US Department of Defense (DoD) from November 2015 to April 2016 revealed 9.4% reported depression.²⁰ Antidepressant usage in the US and among veterans continues to increase.^12,16 In 2018, the list of top US prescribed drugs, included sertraline (14th), citalopram (21st), trazodone (24th), and escitalopram (26th).²¹ Antidepressant prescribing in the US increased 18% from 2012 to 2017.²² This trend also continues within the military with a 40% increase of antidepressant use in the past decade.¹⁶

One reason for the increase in antidepressant use is off-label prescribing.^14,23 A sampling of about 2 billion psychiatric outpatient visits in a western portion of the US found 12.9% of the prescriptions filled were off-label.¹⁵ In Minnesota, off-label prescribing of antidepressants was found to contribute to an increase in drug interactions in elderly nursing home residents.²⁴ An investigation by the Military Times of the military community revealed off-label prescribing occurs not only with antidepressant medications, but also with anticonvulsants, antipsychotics, anti-anxiety drugs, and antiepileptic medications.¹⁴

A case report that brought ST to the forefront occurred in the 1980s and involved a college student.²⁵ She was initially diagnosed with the flu. Her symptoms progressed over a 24-hour period despite treatment, leading to seizures, hyperthermia, generalized clonus, muscle rigidity, respiratory failure, and death because of unrecognized ST. Her combination of serotonin-elevating drugs included meperidine, phenelzine, chlorpheniramine, and haldol. On autopsy, there were traces of cocaine found in some of her tissue samples.

Pathophysiology

Tryptophan is a precursor of serotonin and must be ingested from foods, including meats, dairy, fruits, and seeds. About 90% of all serotonin is made in the gastrointestinal epithelium and is the major component of the brain-gut axis.²⁶ Serotonin cannot cross the blood-brain barrier; therefore, it is synthesized and stored in presynaptic terminals around the midline of the brainstem.^1,26 Transport of serotonin is provided by serotonin transporter (SERT).^1,26,27 Once released, serotonin can either stimulate postsynaptic neuron receptors or is taken up into the presynaptic terminals for reuse. SSRI antidepressants, such as citalopram and paroxetine inhibit the reuptake of serotonin by binding to 2 different sites on the SERT thus allowing more available serotonin to be accessible to other neurons.²⁷ There are 7 families of serotonin receptors, 5-HT1 to 5-HT7 and at least 15 mammalian subtypes.^28,29 The majority of these receptors have been implicated in depression or depressive-like behavior as evidenced by the efficacy of increasing extracellular serotonin for the treatment of depression with SSRIs, SNRIs, TCAs, and MAOIs.²⁹ Three of the most studied receptors include 5-HT_IA,5-HT_1B,and 5-HT_2A.

Etiology

Most serotonin-induced drug fatalities occur when combining serotonergic drugs that work through different pathways (Table 2).³⁰ The most toxic combination of serotonin-enhancing drugs includes MAOIs taken with SSRIs or SNRIs, or a combination of 2 MAOIs.^5-9

Other potentially lethal combinations may includepolypharmacy with antidepressants, pain medications, OTC medications, and illicit drugs. Linezolid, a new synthetic antimicrobial, is considered to be a weak MAOI. Therefore, prescribing it with other serotonin-elevating agents has been reported to precipitate ST.¹⁸

Most cases of ST do not require hospitalization and can be managed by stopping the medication or decreasing the dose. Therapeutic doses of a single drug are highly unlikely to cause toxicity, although there have been reported cases of patients who are sensitive or more susceptible and develop symptoms after administration of a single agent and/or a dosage increase.

Delayed ST reactions have occurred because of a prolonged half-life of a drug, iron deficiency anemia, and coingestion of shorter acting serotonin antagonists.³¹ Most antidepressants have a short half-life (< 24 hours)except for fluoxetine. A decrease in iron may contribute to ST because iron is needed to process serotonin from tryptophan. An example of 2 shorter-acting serotonin antagonists include cyproheptadine and olanzapine. Cyproheptadine is used in the treatment of ST, and olanzapine is an antipsychotic.

Symptoms

Symptoms of ST range from mild to severe and include a combination of neuromuscular, autonomic, and mental status changes (Table 3).^5,10 Mild symptoms of ST can start within 1 to 2 hours after ingesting a medication that increases serotonin to a toxic state unless the drug has a long half-life (eg, fluoxetine). Sometimes mild symptoms of ST can be difficult to distinguish from common drug AEs, flu symptoms, or viruses. Patients taking therapeutic doses of SSRIs can experience serotonin symptoms, such as lower limb hyperreflexia or a few beats of ankle clonus without being toxic. One thing to remember is that not all patients will start with mild symptoms and may present in moderate or severe distress.

Moderate-to-severe ST symptoms require hospitalization, usually in the intensive care unit (ICU). At this stage, clonus progresses from the lower extremities to the upper body and becomes more generalized. Ocular clonus can be continuous, intermittent, or have a ping pong effect (short cycle, periodic, alternating lateral gaze).

Severe ST is life threatening and leads to multiorgan failure within hours if not treated. The patient is intubated to assist with breathing and sedated because excess agitation and muscular tremors can increase temperature, which is already elevated by the time the symptoms reach the severe state. Of note, hyperthermia is due to a noninfectious elevation of body temperature from hypertonicity, agitation, and muscle rigidity.A true core temperature > 105.8°F causes irreversible cell damage, cerebral injury, and death.^32,33 The patient can develop seizures and a coma. Multiorgan failure occurs, including rhabdomyolysis, myoglobinuria, renal failure, metabolic acidosis, acute respiratory distress, and disseminated intravascular coagulation.

Diagnosis

The diagnosis of ST is clinical and based on a history of ingesting serotonin-elevating medications and physical findings as per Hunter Serotonin Toxicity Criteria³⁴ (Table 4). An in-depth history needs to include previous and current prescriptions, indications of the prescriptions (eg, therapeutic, increase in dosage, suicide intent), OTC medications, and illicit drug use. Early recognition of symptoms, identification of serotonergic medications, and appropriate resuscitative measures lead to more successful outcomes. A serotonin drug level is ineffective and does not correlate with the dosage since serotonin does not cross the blood-brain barrier.

The type of drug determines the length and response of the episode. The drug(s) elimination half-lives need to be calculated along with the pharmacokinetic or pharmacodynamics; agonist, antagonist, reuptake inhibitor, etc. Many drugs have half-lives of < 24 hours; therefore, reducing or eliminating the offending drug(s) will result in a steady reduction of symptoms.Exceptions include medications with a longer activity, such as the irreversible MAOIs (eg, phenelzine, isocarboxazid) and drugs with a longer half-life, such as fluoxetine. These types of medications may have been stopped weeks earlier and may prolong reduction of symptoms.

When initiating or increasing SSRIs or SNRIs, there are common nontoxic AEs that are not consistent with ST, including anxiety, restlessness, and irritability that may last for 2 weeks. The difference in toxic vs nontoxic reactions are the timing and rapid progression of symptoms. The toxic symptoms will start within hours of ingesting the offending agents(s) and progress rapidly to severe symptoms within 24 hours. Therefore, it is imperative to review AEs with the patient and or caregiver, so they may act as their own advocate and seek immediate assistance.

Differentials

There are symptoms specific to ST that can be used to differentiate it from other conditions. These include hyperthermia, bilateral symmetric clonus (inducible, spontaneous, ocular), and hyperreflexia.These criteria form the basis for Hunter criteria.

Differential diagnoses to consider include neuroleptic malignant syndrome; antidepressant initiation AEs; antidepressant discontinuation syndrome; malignant hyperthermia; anticholinergic toxicity; meningitis/encephalitis; sepsis; drug overdose; alcohol/benzodiazepine withdrawal; and preeclampsia. Neuroleptic malignant syndrome (NMS) is the disorder most often misdiagnosed as ST.Key elements that distinguish ST from NMS include the timing of the clinical course (NMS develops over days to weeks); the medications ingested (NMS from dopaminergic drugs); and the symptoms of NMS (bradyreflexia, bradykinesia, bradyphrenia, and no clonus).According to Gillman, serotonin toxicity is a manifestation of toxicity that is predictable and common with specific drug combinations, while NMS is a “rare idiosyncratic reaction to essentially normal doses and very rarely occurs after overdoses.”³⁵ Preeclampsia is a pregnancy complication that can mimic ST with symptoms of hypertension, clonus, and hyperreflexia. It has been estimated to complicate 2% to 8% of pregnancies and remains a principle cause of maternal and fetal morbidity and mortality.^36,37

Treatment

Mild-to-moderate symptoms usually resolve on their own 1 to 3 days after decreasing or stopping the offending drug. The timing will depend on the half-life or active metabolites of the drug. Treatment is largely supportive and may require treatment for control of agitation with benzodiazepines and IV fluids for dehydration/hypotension.¹⁴ In cases not responding to supportive care, treatment with oral cyproheptadine is recommended.¹⁴

There are other medications that have been used in treatment such as olanzapine, chlorpromazine, propranolol, bromocriptine, dantrolene, droperidol, and haloperidol, but their efficacy is unproven and not recommended.¹⁰ Chlorpromazine can cause hypotension and increase hyperthermia. Propranolol has a long duration of action, may cause a prolonged hypotension, and can mask tachycardia that can be used to monitor the effectiveness of treatment.¹⁰ Bromocriptine is a serotonin agonist and may exacerbate symptoms. Dantrolene has no effect on survival in animal models.¹⁰ Droperidol and haloperidol can worsen hyperthermia by inhibiting sweating.³⁸

Mechanical ventilation should be considered especially if muscle rigidity progresses and depressed respiratory function occurs. If the temperature starts to rise, immediate sedation, paralysis, mechanical ventilation, and cyproheptadine are administered.The overall goal is prevention of hyperthermia, which leads to multiorgan failure. A core temperature of ≥ 104°F is associated with neurologic cell death, and recovery is minimal.³² Consultation with an experienced toxicologist is strongly recommended.Antipyretics should not be used, because elevated temperature is centrally mediated from muscle rigidity. If presentation occurs within 1 hour, activated charcoal can be used for detoxification of potentially lethal amounts.

Warning Label Controversies

In 2006, the US Food and Drug Administration (FDA) issued an advisory warning against concurrently using a tryptan antimigraine drug and serotonin-mediated medications.³⁹ In 2018, a research team conducted a 14-year retrospective analysis on 20,000 patients who were coprescribed a tryptan drug with SSRIs or SNRIs.⁴⁰ The study reported that the risk of ST was rare and suggested that the FDA reconsider their advisory. There are several other controversial medications with a ST FDA warning label due to their mechanisms of action and inaccurate case reports.⁴¹

Human Poisonings

Consistent with the 2017 American Association of Poison Control Centers Toxic Exposure report, antidepressants continue to be in the top 5 substance classes most frequently involved in human exposures.⁴² Most accidental ingestions of antidepressants occur in toddlers, whereas intentional ingestions are usually done by adolesents.⁴³ Over the past 10 years, antidepressants are the No. 1 fastest growing category of human exposures in all age groups.⁴²

ST in the Pediatric Population

ST in the pediatric population mirrors that in adults.Differences include the inability of the child to report symptoms, lack of clinician awareness, and reluctance of adolescents to disclose recreational drug use.Management is the same as for adults, including discontinuing the offending drug, supportive care, adequate sedation, oxygen, IV fluids, and continuous cardiac monitoring. Sedation is weight based for benzodiazepines. Mild-to-moderate reactions require admission for observation. Severe reactions require admission to the ICU.

There have been at least 4 published case reports of children aged < 6 years with moderate-to-severe ST secondary to acute vilazodone ingestion.⁴⁴ The dosages included 5.5 to 37 mg/kg. All 4 patients had altered mental status, seizures, hyperthermia, mild clonus, tachycardia, and hypertension. They all survived with intensive care treatment, including intubation, sedation, cyproheptadine in 2 cases, activated charcoal and IV lorazepam in the other cases.

Direk and colleagues reported a case of a 12-year-old girl who was brought to the emergency department by her stepmother for seizurelike activity and was diagnosed with epilepsy and status epilepticus.⁴⁵ In the pediatric ICU she developed tachycardia, fever, agitation, dilated pupils, tremors, increased deep tendon reflexes, spontaneous clonus, and horizontal ocular movements. A detailed clinical history was retaken and revealed that the child had been prescribed risperidone 1 week before by the psychiatric clinic due to behavioral problems, including stealing money, lying, and running away from home and school. On further investigation, the stepmother was taking clomipramine and discovered 9 missing pills.

Pregnancy and Lactation

The American College of Obstetricians and Gynecologists recommends that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms, using a standardized, validated tool and complete a full assessment of mood and emotional well-being during the postpartum, including screening for postpartum depression and anxiety with a validated instrument.⁴⁶ Treatment with antidepressants is controversial. “Current evidence is generally reassuring and indicates that the absolute risks of negative infant outcomes are small except for PNAS [poor neonatal adaptation syndrome], which largely appears to be self-limited.”⁴⁷ Antidepressants cross the human placenta and fetal blood-brain barrier.⁴⁸ Several cases of infant toxicity from SSRIs have been reported with citalopram and escitalopram.^49,50 Symptoms included severe muscle rigidity, lethargy, tachycardia, QTc prolongation, altered consciousness, hypertonia, and seizures at birth. These mothers had taken an SSRI during pregnancy.

Conclusions

This article highlights some of the latest information on ST. Increased awareness of all clinicians and their patients may help decrease unnecessary comorbidities and death. Early identification of ST symptoms will increase the chances for survival, because of the rapid progression of symptoms within 24 hours. Most fatal reactions occur when combining MAOIs with SSRIs, SNRIs, or another MAOI. Overdose with an SSRI does not progress to the severe symptoms unless combined with another serotonin-elevating medication.

Education of all patients who are prescribed antidepressants must include awareness of the potential for serotonergic drug interactions, particularly from OTC medications, herbal medications, and illicit drugs. The diagnosis of ST is based on clinical findings and there must be a history of ingesting serotonin-elevating drug(s). Hunter Serotonin Toxicity Criteria is the gold standard for diagnosing symptoms along with consulting a toxicologist. Prevention of ST includes informed clinicians, patient education, careful prescribing and monitoring, and avoidance of multidrug regimens.

Serotonin, or 5-hydroxytryptamine (5-HT), is a chemical neurotransmitter in the central and peripheral nervous systems that was discovered in 1940s. ¹ O ne of the most widely studied chemical messengers , serotonin influences many physiologic functions in humans, including regulation of mood, sleep-wake cycle, appetite suppression, memory, emesis, breathing, cognition, blood coagulation, libido, and many other functions. ² In 1992, Insel and colleagues first document ed the toxic symptoms produced from too much serotonin in the central and peripheral nervous systems , naming it serotonin syndrome. ^3,4

Serotonin Syndrome

Experts in the fields of psychiatry, pharmacy, and toxicology refer to these symptoms as serotonin toxicity, because the symptoms result from the toxic effects of too much serotonin.^5-9 The term toxicity instead of syndrome “clarifies that it is a form of poisoning, just as lithium toxicity is a form of poisoning.”⁶ Therefore, serotonin toxicity (ST) can develop with administration of any serotonin-enhancing medication, including therapeutic use, polypharmacy, or accidental/intentional drug overdose.

The incidence of ST has increased over the past decade.^5,6,10,11 Several reasons explain this increase: (1) ST mirrors the increase in depression in the US populations^10,12,13; (2) There has been an increase in off-label antidepressant prescribing by both primary care and mental health providers^14-16; (3) the increased use of illicit drugs¹³; (4) an increase in suicide attempts with antidepressants¹⁷; and (5) increased use of opioids for pain management, including both prescription and illicit use.^11,14 This paper reviews the potential lethal combinations of commonly prescribed medications used to treat both veteran and nonveteran patients and includes the latest information on offending medications; a presentation of symptoms from in utero to adult; diagnostic criteria; and recommended treatments.

The Veterans Health Administration (VHA) and non-VHA health care providers can play a key role in identifying and preventing serotonin syndrome/ST by keeping abreast of the latest updates of potentially lethal drug combinations. Commonly prescribed medications with the potential for a reaction include antidepressants, anxiolytics, pain medications, antinausea medications, herbal medications, and over-the-counter (OTC) medications, such as cough suppressants. Patients may be at increased risk for ST due to the growth of polypharmacy management of comorbidities.

Antidepressants

Over the past decade, antidepressant use has increased substantially in the US,United Kingdom, and Canada.¹⁴ Also the types of antidepressants prescribed has changed and been replaced with the newer agents. The selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have replaced the older tricyclics (TCAs) and monoamine oxidase inhibitors (MAOIs) as first-line treatments for depression due to their improved comparative efficacy, reduced mortality following overdose, adverse effects (AEs) that are more tolerable for most patients, and the SSRIs have no anticholinergic properties (except paroxetine) (Table 1).¹⁸

In 2017 the National Institute of Mental Health reported that about 17 million adults and 3 million adolescents (aged 11-18 years) experienced at least 1 episode of major depression.¹⁹ About 40% of US veterans will experience depression, which is 3 times higher than the rate of the general US population.¹² A random sampling survey conducted of about 17,000 active-duty service members by the US Department of Defense (DoD) from November 2015 to April 2016 revealed 9.4% reported depression.²⁰ Antidepressant usage in the US and among veterans continues to increase.^12,16 In 2018, the list of top US prescribed drugs, included sertraline (14th), citalopram (21st), trazodone (24th), and escitalopram (26th).²¹ Antidepressant prescribing in the US increased 18% from 2012 to 2017.²² This trend also continues within the military with a 40% increase of antidepressant use in the past decade.¹⁶

One reason for the increase in antidepressant use is off-label prescribing.^14,23 A sampling of about 2 billion psychiatric outpatient visits in a western portion of the US found 12.9% of the prescriptions filled were off-label.¹⁵ In Minnesota, off-label prescribing of antidepressants was found to contribute to an increase in drug interactions in elderly nursing home residents.²⁴ An investigation by the Military Times of the military community revealed off-label prescribing occurs not only with antidepressant medications, but also with anticonvulsants, antipsychotics, anti-anxiety drugs, and antiepileptic medications.¹⁴

A case report that brought ST to the forefront occurred in the 1980s and involved a college student.²⁵ She was initially diagnosed with the flu. Her symptoms progressed over a 24-hour period despite treatment, leading to seizures, hyperthermia, generalized clonus, muscle rigidity, respiratory failure, and death because of unrecognized ST. Her combination of serotonin-elevating drugs included meperidine, phenelzine, chlorpheniramine, and haldol. On autopsy, there were traces of cocaine found in some of her tissue samples.

Pathophysiology

Tryptophan is a precursor of serotonin and must be ingested from foods, including meats, dairy, fruits, and seeds. About 90% of all serotonin is made in the gastrointestinal epithelium and is the major component of the brain-gut axis.²⁶ Serotonin cannot cross the blood-brain barrier; therefore, it is synthesized and stored in presynaptic terminals around the midline of the brainstem.^1,26 Transport of serotonin is provided by serotonin transporter (SERT).^1,26,27 Once released, serotonin can either stimulate postsynaptic neuron receptors or is taken up into the presynaptic terminals for reuse. SSRI antidepressants, such as citalopram and paroxetine inhibit the reuptake of serotonin by binding to 2 different sites on the SERT thus allowing more available serotonin to be accessible to other neurons.²⁷ There are 7 families of serotonin receptors, 5-HT1 to 5-HT7 and at least 15 mammalian subtypes.^28,29 The majority of these receptors have been implicated in depression or depressive-like behavior as evidenced by the efficacy of increasing extracellular serotonin for the treatment of depression with SSRIs, SNRIs, TCAs, and MAOIs.²⁹ Three of the most studied receptors include 5-HT_IA,5-HT_1B,and 5-HT_2A.

Etiology

Most serotonin-induced drug fatalities occur when combining serotonergic drugs that work through different pathways (Table 2).³⁰ The most toxic combination of serotonin-enhancing drugs includes MAOIs taken with SSRIs or SNRIs, or a combination of 2 MAOIs.^5-9

Other potentially lethal combinations may includepolypharmacy with antidepressants, pain medications, OTC medications, and illicit drugs. Linezolid, a new synthetic antimicrobial, is considered to be a weak MAOI. Therefore, prescribing it with other serotonin-elevating agents has been reported to precipitate ST.¹⁸

Most cases of ST do not require hospitalization and can be managed by stopping the medication or decreasing the dose. Therapeutic doses of a single drug are highly unlikely to cause toxicity, although there have been reported cases of patients who are sensitive or more susceptible and develop symptoms after administration of a single agent and/or a dosage increase.

Delayed ST reactions have occurred because of a prolonged half-life of a drug, iron deficiency anemia, and coingestion of shorter acting serotonin antagonists.³¹ Most antidepressants have a short half-life (< 24 hours)except for fluoxetine. A decrease in iron may contribute to ST because iron is needed to process serotonin from tryptophan. An example of 2 shorter-acting serotonin antagonists include cyproheptadine and olanzapine. Cyproheptadine is used in the treatment of ST, and olanzapine is an antipsychotic.

Symptoms

Symptoms of ST range from mild to severe and include a combination of neuromuscular, autonomic, and mental status changes (Table 3).^5,10 Mild symptoms of ST can start within 1 to 2 hours after ingesting a medication that increases serotonin to a toxic state unless the drug has a long half-life (eg, fluoxetine). Sometimes mild symptoms of ST can be difficult to distinguish from common drug AEs, flu symptoms, or viruses. Patients taking therapeutic doses of SSRIs can experience serotonin symptoms, such as lower limb hyperreflexia or a few beats of ankle clonus without being toxic. One thing to remember is that not all patients will start with mild symptoms and may present in moderate or severe distress.

Moderate-to-severe ST symptoms require hospitalization, usually in the intensive care unit (ICU). At this stage, clonus progresses from the lower extremities to the upper body and becomes more generalized. Ocular clonus can be continuous, intermittent, or have a ping pong effect (short cycle, periodic, alternating lateral gaze).

Severe ST is life threatening and leads to multiorgan failure within hours if not treated. The patient is intubated to assist with breathing and sedated because excess agitation and muscular tremors can increase temperature, which is already elevated by the time the symptoms reach the severe state. Of note, hyperthermia is due to a noninfectious elevation of body temperature from hypertonicity, agitation, and muscle rigidity.A true core temperature > 105.8°F causes irreversible cell damage, cerebral injury, and death.^32,33 The patient can develop seizures and a coma. Multiorgan failure occurs, including rhabdomyolysis, myoglobinuria, renal failure, metabolic acidosis, acute respiratory distress, and disseminated intravascular coagulation.

Diagnosis

The diagnosis of ST is clinical and based on a history of ingesting serotonin-elevating medications and physical findings as per Hunter Serotonin Toxicity Criteria³⁴ (Table 4). An in-depth history needs to include previous and current prescriptions, indications of the prescriptions (eg, therapeutic, increase in dosage, suicide intent), OTC medications, and illicit drug use. Early recognition of symptoms, identification of serotonergic medications, and appropriate resuscitative measures lead to more successful outcomes. A serotonin drug level is ineffective and does not correlate with the dosage since serotonin does not cross the blood-brain barrier.

The type of drug determines the length and response of the episode. The drug(s) elimination half-lives need to be calculated along with the pharmacokinetic or pharmacodynamics; agonist, antagonist, reuptake inhibitor, etc. Many drugs have half-lives of < 24 hours; therefore, reducing or eliminating the offending drug(s) will result in a steady reduction of symptoms.Exceptions include medications with a longer activity, such as the irreversible MAOIs (eg, phenelzine, isocarboxazid) and drugs with a longer half-life, such as fluoxetine. These types of medications may have been stopped weeks earlier and may prolong reduction of symptoms.

When initiating or increasing SSRIs or SNRIs, there are common nontoxic AEs that are not consistent with ST, including anxiety, restlessness, and irritability that may last for 2 weeks. The difference in toxic vs nontoxic reactions are the timing and rapid progression of symptoms. The toxic symptoms will start within hours of ingesting the offending agents(s) and progress rapidly to severe symptoms within 24 hours. Therefore, it is imperative to review AEs with the patient and or caregiver, so they may act as their own advocate and seek immediate assistance.

Differentials

There are symptoms specific to ST that can be used to differentiate it from other conditions. These include hyperthermia, bilateral symmetric clonus (inducible, spontaneous, ocular), and hyperreflexia.These criteria form the basis for Hunter criteria.

Differential diagnoses to consider include neuroleptic malignant syndrome; antidepressant initiation AEs; antidepressant discontinuation syndrome; malignant hyperthermia; anticholinergic toxicity; meningitis/encephalitis; sepsis; drug overdose; alcohol/benzodiazepine withdrawal; and preeclampsia. Neuroleptic malignant syndrome (NMS) is the disorder most often misdiagnosed as ST.Key elements that distinguish ST from NMS include the timing of the clinical course (NMS develops over days to weeks); the medications ingested (NMS from dopaminergic drugs); and the symptoms of NMS (bradyreflexia, bradykinesia, bradyphrenia, and no clonus).According to Gillman, serotonin toxicity is a manifestation of toxicity that is predictable and common with specific drug combinations, while NMS is a “rare idiosyncratic reaction to essentially normal doses and very rarely occurs after overdoses.”³⁵ Preeclampsia is a pregnancy complication that can mimic ST with symptoms of hypertension, clonus, and hyperreflexia. It has been estimated to complicate 2% to 8% of pregnancies and remains a principle cause of maternal and fetal morbidity and mortality.^36,37

Treatment

Mild-to-moderate symptoms usually resolve on their own 1 to 3 days after decreasing or stopping the offending drug. The timing will depend on the half-life or active metabolites of the drug. Treatment is largely supportive and may require treatment for control of agitation with benzodiazepines and IV fluids for dehydration/hypotension.¹⁴ In cases not responding to supportive care, treatment with oral cyproheptadine is recommended.¹⁴

There are other medications that have been used in treatment such as olanzapine, chlorpromazine, propranolol, bromocriptine, dantrolene, droperidol, and haloperidol, but their efficacy is unproven and not recommended.¹⁰ Chlorpromazine can cause hypotension and increase hyperthermia. Propranolol has a long duration of action, may cause a prolonged hypotension, and can mask tachycardia that can be used to monitor the effectiveness of treatment.¹⁰ Bromocriptine is a serotonin agonist and may exacerbate symptoms. Dantrolene has no effect on survival in animal models.¹⁰ Droperidol and haloperidol can worsen hyperthermia by inhibiting sweating.³⁸

Mechanical ventilation should be considered especially if muscle rigidity progresses and depressed respiratory function occurs. If the temperature starts to rise, immediate sedation, paralysis, mechanical ventilation, and cyproheptadine are administered.The overall goal is prevention of hyperthermia, which leads to multiorgan failure. A core temperature of ≥ 104°F is associated with neurologic cell death, and recovery is minimal.³² Consultation with an experienced toxicologist is strongly recommended.Antipyretics should not be used, because elevated temperature is centrally mediated from muscle rigidity. If presentation occurs within 1 hour, activated charcoal can be used for detoxification of potentially lethal amounts.

Warning Label Controversies

In 2006, the US Food and Drug Administration (FDA) issued an advisory warning against concurrently using a tryptan antimigraine drug and serotonin-mediated medications.³⁹ In 2018, a research team conducted a 14-year retrospective analysis on 20,000 patients who were coprescribed a tryptan drug with SSRIs or SNRIs.⁴⁰ The study reported that the risk of ST was rare and suggested that the FDA reconsider their advisory. There are several other controversial medications with a ST FDA warning label due to their mechanisms of action and inaccurate case reports.⁴¹

Human Poisonings

Consistent with the 2017 American Association of Poison Control Centers Toxic Exposure report, antidepressants continue to be in the top 5 substance classes most frequently involved in human exposures.⁴² Most accidental ingestions of antidepressants occur in toddlers, whereas intentional ingestions are usually done by adolesents.⁴³ Over the past 10 years, antidepressants are the No. 1 fastest growing category of human exposures in all age groups.⁴²

ST in the Pediatric Population

ST in the pediatric population mirrors that in adults.Differences include the inability of the child to report symptoms, lack of clinician awareness, and reluctance of adolescents to disclose recreational drug use.Management is the same as for adults, including discontinuing the offending drug, supportive care, adequate sedation, oxygen, IV fluids, and continuous cardiac monitoring. Sedation is weight based for benzodiazepines. Mild-to-moderate reactions require admission for observation. Severe reactions require admission to the ICU.

There have been at least 4 published case reports of children aged < 6 years with moderate-to-severe ST secondary to acute vilazodone ingestion.⁴⁴ The dosages included 5.5 to 37 mg/kg. All 4 patients had altered mental status, seizures, hyperthermia, mild clonus, tachycardia, and hypertension. They all survived with intensive care treatment, including intubation, sedation, cyproheptadine in 2 cases, activated charcoal and IV lorazepam in the other cases.

Direk and colleagues reported a case of a 12-year-old girl who was brought to the emergency department by her stepmother for seizurelike activity and was diagnosed with epilepsy and status epilepticus.⁴⁵ In the pediatric ICU she developed tachycardia, fever, agitation, dilated pupils, tremors, increased deep tendon reflexes, spontaneous clonus, and horizontal ocular movements. A detailed clinical history was retaken and revealed that the child had been prescribed risperidone 1 week before by the psychiatric clinic due to behavioral problems, including stealing money, lying, and running away from home and school. On further investigation, the stepmother was taking clomipramine and discovered 9 missing pills.

Pregnancy and Lactation

The American College of Obstetricians and Gynecologists recommends that clinicians screen patients at least once during the perinatal period for depression and anxiety symptoms, using a standardized, validated tool and complete a full assessment of mood and emotional well-being during the postpartum, including screening for postpartum depression and anxiety with a validated instrument.⁴⁶ Treatment with antidepressants is controversial. “Current evidence is generally reassuring and indicates that the absolute risks of negative infant outcomes are small except for PNAS [poor neonatal adaptation syndrome], which largely appears to be self-limited.”⁴⁷ Antidepressants cross the human placenta and fetal blood-brain barrier.⁴⁸ Several cases of infant toxicity from SSRIs have been reported with citalopram and escitalopram.^49,50 Symptoms included severe muscle rigidity, lethargy, tachycardia, QTc prolongation, altered consciousness, hypertonia, and seizures at birth. These mothers had taken an SSRI during pregnancy.

Conclusions

This article highlights some of the latest information on ST. Increased awareness of all clinicians and their patients may help decrease unnecessary comorbidities and death. Early identification of ST symptoms will increase the chances for survival, because of the rapid progression of symptoms within 24 hours. Most fatal reactions occur when combining MAOIs with SSRIs, SNRIs, or another MAOI. Overdose with an SSRI does not progress to the severe symptoms unless combined with another serotonin-elevating medication.

Education of all patients who are prescribed antidepressants must include awareness of the potential for serotonergic drug interactions, particularly from OTC medications, herbal medications, and illicit drugs. The diagnosis of ST is based on clinical findings and there must be a history of ingesting serotonin-elevating drug(s). Hunter Serotonin Toxicity Criteria is the gold standard for diagnosing symptoms along with consulting a toxicologist. Prevention of ST includes informed clinicians, patient education, careful prescribing and monitoring, and avoidance of multidrug regimens.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

An ADHD brain thrives with daily routines, and requires spontaneity and challenge to remain engaged in work, academics, relationships, and even leisure activities. ADHD is a performance issue and not one of intellectual understanding. It is not a problem of knowing what to do, but rather, difficulty doing it.

The COVID-19 pandemic has led to the loss of structure, with many parents working out of their homes alongside their children engaged in virtual learning. There has been a significant loss of impromptu events, since all activities outside of the house require proper planning and safety precautions.

To help normalize the struggles of the adult patient with ADHD during the pandemic, I have compiled a list of everything I want my adult ADHD patients and their family members to know so they don’t feel shame, guilt, or hopelessness when others’ coping strategies do not work for their ADHD brains.
 

Adult ADHD is a misnomer – and not just a disorder of inattention and hyperactivity

A better name for this often misconstrued disorder is inconsistent attention and motivation disorder with internal or external hyperactivity/impulsivity.

An ADHD brain vacillates between inattention and hyperfocus. It is not uncommon for individuals with ADHD to lose interest in a new television series when they become hyperfocused on finding the best pandemic-friendly toy for their 5-year-olds, which inevitably turns into a 3-hour Google rabbit-hole search.

These same individuals with ADHD may have low motivation for mundane household chores but become highly motivated when their nonessential Amazon purchases arrive. They may even go as far as pulling an all-nighter to have an electric toy jeep built and ready for the youngster by morning.

Adults with ADHD can also exhibit hyperactive symptoms, such as physical restlessness with fidgeting, and an internal restlessness with anxious and repetitive thoughts that affect their ability to unwind, relax, and even sleep. Impulsivity in adults with ADHD can present as rushing through tasks that one finds uninteresting or unimportant, interrupting others on a Zoom work call, or impulse buying an expensive hot tub instead of a more affordable on their spouse agreed to.
 

ADHD is a risk factor for contracting COVID-19

Untreated ADHD can increase one’s risk of contracting COVID-19. Israeli researchers published a study in the Journal of Attention Disorders showing that individuals with ADHD are 52% more likely to test positive for COVID-19, compared with those without ADHD, because of risk-taking behaviors, impulsivity, and carelessness. However, individuals whose ADHD symptoms are treated with stimulant medication do not increase their risk of contracting COVID-19, the researchers wrote.

ADHD might be noticed in family members

ADHD is a neurodevelopmental disorder that affects the development of the brain. We know that structural, functional, and chemical differences affect our patients’ ability to regulate attention, motivation, impulses, and emotions. ADHD tends to run in families and is highly genetic. Since spending more time with family members during the pandemic, patients might even recognize ADHD symptoms in siblings, children, and one or both of parents. A child who has ADHD has a 25% chance of having a parent with ADHD.

Strengths and attributes are related to ADHD

Your ability to thrive in new, stressful, and challenging situations is an ADHD attribute that will be beneficial during the pandemic. Creativity, great problem-solving skills, and ability to be flexible will be admired and helpful to our patients with ADHD and others during these uncertain times.

Those with ADHD might be highly sensitive to their environments

As previously mentioned, ADHD is a misnomer and not just a disorder of inattention but also too much attention. Unfortunately, this hyperfocused attention is usually on the wrong things. Those with ADHD might find it difficult to filter and process sensory information correctly and, therefore, can be easily distracted by auditory, visual, tactile, and olfactory stimuli. The change to working at home during the pandemic might make it hard to ignore children’s voices, the uncomfortable new mask bought after losing yet another mask over the weekend, and the smell of cookies emanating from the kitchen. This increased sensitivity may affect one’s emotions.

Heightened emotions are expected during the pandemic and even more so among adults with ADHD. The inability of adults with ADHD to properly filter information can also affect emotional stimuli. These intense emotions, coupled with impulsive behaviors, can cause disagreements with partners, lack of patience with children, and conflict with colleagues. When individuals with ADHD feel attacked or invalidated, they can become emotionally dysregulated and “vomit” their pent up feelings.
 

ADHD may affect interpersonal relationships

ADHD symptoms of inattention and impulsivity can affect the ability to connect with friends and family. When one is easily distracted by the pandemic’s chaos, it is harder to be mindful and emotionally and physically connected to one’s partner, which also disrupts their sex life and intimacy.

ADHD sensory integration issues can make people sensitive to particular touches, smells, and sensory information. A gentle touch from one’s partner might be annoying during the pandemic, since other senses may already be overstimulated by the loud sounds of children screaming, the visual and auditory distractions of a neighbor mowing the lawn, and the sun beating down because one forgot to get blinds in the home office before the pandemic.

These minor distractions that are usually insignificant to a non-ADHD brain can profoundly affect an ADHD brain since one must use valuable energy to tune out these unwanted disturbances.
 

Your brain uses a different motivational system than a non-ADHD brain

You have a deficiency in the neurotransmitter dopamine, which affects your motivational system. Your motivational system is based on what you find interesting, challenging, new, exciting, and urgent. Your non-ADHD partner, family members, friends, and colleagues motivate and accomplish their daily tasks differently from you and most likely use a system based on rewards and consequences.

Do not be surprised if you notice that your motivation is diminished during the pandemic because of less novelty and excitement in your life. The coronavirus’s chronic importance level may make everything else in your life not as essential and, therefore, less urgent, which indirectly also lowers your motivation.

Your non-ADHD partner may see that you can focus, prioritize, initiate, and complete tasks when you “choose” to, and confuse your inconsistent behaviors as being within your control. However, this lack of motivation for things that do not pique your interest, challenge you, and are not urgent is not voluntary. It is caused by a lack of neural connections in the area of the brain that controls motivation.
 

You can still have ADHD even though you were not diagnosed as a child or adolescent

Your symptoms of ADHD may not affect your level of functioning until you go away to college, obtain your first job, marry your partner, start a family, or even until a global pandemic alters every aspect of your daily life.

It is, therefore, never too late to get assessed and treated for ADHD. Stimulants are the first line of treatment for adult ADHD. Nonstimulants may also be prescribed if you do not tolerate the side effects of stimulants or have a history of certain medical conditions. These options include some antidepressants and high blood pressure medicines. Sometimes, just identifying the deficits of those with ADHD and how they may affect their performance at work, school, and interpersonal relationships can help the person living with ADHD. Many other any nonmedication types of effective treatment are available for adults with ADHD, including therapy, executive skills, and mindfulness training.

• ADHD focused cognitive-behavioral therapy can help one change your distorted, negative, and irrational thoughts about themselves, others, and situations and replace them with more realistic and rational thoughts that allow for helpful and adaptive behaviors.
• Executive skills training is a type of ADHD treatment that focuses on developing effective systems, routines, improving time management, organization, planning, productivity, and emotional self-regulation.
• Mindfulness meditation training is an additional treatment for adult ADHD. Mindfulness training teaches skills to focus on the present moment and become aware of one’s thoughts, emotions, and actions without judgment. The goal is to learn to accept your ADHD deficits and all that is out of your control while remaining mindful of your ADHD strengths and focusing on the daily choices within your control.

Silver linings of the pandemic

Numerous underserved and rural geographic areas lack adequate psychiatric care. Many primary care physicians and even some psychiatrists are uncomfortable diagnosing and treating attentional disorders because of a lack of proper training in medical school and fear related to the fact that the first-line treatment for adult ADHD is a controlled substance.

In response to the pandemic, the expansion of telepsychiatry services, state waivers that allow clinicians to practice across state lines, exemptions that enable the prescribing of controlled substances without an in-person medical evaluation, and the acceptance of employees working from home during the COVID-19 pandemic have increased the accessibility of adult ADHD psychiatric assessments and treatment.

It is hoped that when the COVID-19 pandemic is behind us, many of the benefits that have emerged, such as the growth of telepsychiatry, changes in state licensure and prescriber regulations, and reduced work commutes will continue into our postpandemic lives.
 

Dr. Abraham is a psychiatrist in private practice in Philadelphia. She has no disclosures.

Successful athletes exhibit positive mental health. This mental health is directly related to athletic success and high levels of performance.¹ Mental skills are as important as natural physical ability and mechanical skills in the sport of tennis.

Research has shown that tennis is 85% mental and that players spend 80% of their time on the court handling emotions. Some players look good in practice when they are not under pressure but cannot win matches (they have the physical skill level to win) because they cannot handle their own emotions during the duress of a match. They are affected by anger, fear, stress, poor concentration, and other internal elements that interfere with their ability to perform at an optimal level. Competitors may also be affected by external factors such as the sun, wind, an opponent, and so on, and may use these situations as an excuse not to win.

Players normally practice physical skills but rarely practice cognitive techniques. Regardless of level of play – pro, collegiate, junior, or club – practicing mental skills will greatly improve the players’ arsenal of weapons, giving them an edge in matches and making them the best players they can be. Mental health professionals also can use these strategies to help motivate athletes who compete in other sports – and in other competitive endeavors.

Visualization is the formation of a mental image of something of your choice. Visualization imagery techniques can be used by players to calm themselves before playing a match so their emotions are not wasted on trying to quiet the minds and quell stress. Implementing the following visualization techniques will reduce a player’s anxiety during the match, allowing the player to direct energy toward optimal mental and physical performance on the court.

In advance of a match, encourage the player to learn and analyze the opponent’s strengths and weaknesses by watching the opponent play and/or from asking others. The night before the scheduled match, get the player to imagine how they will play points against their competitor. Play into the opponents’ vulnerabilities or first play to their strengths to expose shortcomings and – then attack their weakness. For example, if an opponent has a weak backhand, first play to the opponent’s forehand and, when the opponent is vulnerable, go into his backhand to get a short or weak ball – and attack. The following are specific strategies that mental health professionals who work with athletes can use to help them perform optimally.
 

Using visualization, shadowing

Visualize the correct way to hit a tennis stroke and repeat it over and over in your mind. On a tennis court or where ever you have adequate space, shadow a stroke by using a racket and repetitively performing the actual stroke without hitting a ball. At home, practice relaxation and deep breathing techniques at night before going to sleep. Put yourself in a relaxed state and visualize repetitively striking the ball correctly. The next time you actually hit the stroke, you will produce a better shot.

Focusing on, staying in the here and now

The “here” means to focus on what is happening on your own court, not what is happening on the court next to you. Players may be affected by external factors, such as the sun, wind, and their opponent and may use these conditions or situations as an excuse if they do not win. Ignore background chatter and distractions, and be a horse with blinders. Be responsible for yourself and your own actions; manage what you can and realize that you cannot control the weather or actions of your opponent.

The “now” refers to staying present and focusing only on the current point. Do not think of past mistakes. If you are winning a match, do not think about celebrating while the match is still in play. If you are losing, do not start to write a script of excuses why you lost the match. Instead, just concentrate on the present, point by point. Focusing will allow you to understand what is true and important in the here and now. Focusing will help alleviate stress and better equip you to make quick decisions and be clear about your intended actions.
 

Set realistic and achievable goals

It is always good to have goals and dreams; however, you as a player must understand the realities of your current level of play. Know your level; don’t be grandiose and think you are able to beat Rafael Nadal. Having an unrealistic attitude will result in frustration and poor performance during a match. Instead, set achievable, and realistic short- and long-term goals for yourself, which will aid in your overall tennis development. After the match is over, reflect upon and evaluate the points – and your overall performance.

Don’t devalue yourself if you lose a match. Do not feel too low from a loss or too high from a win. When you have a match loss, use it as an opportunity to learn from your mistakes and to improve by working on your weaknesses in future practice until you feel confident enough to use your new skills in a tournament.
 

Stay positive

Do not tie up your self-esteem as a person with your match outcome; in otherwords, separate feelings of self-worth from your match results. Cultivate an optimistic attitude and talk positively to yourself, strive to improve, and maintain positive self-esteem in practice and in matches. During practice, allocate 110% effort, and focus on the process, not the outcome. Arrange your practice matches so that one-third of them are against players of your same level, one-third against players worse than you, and one-third against players better than yourself.

Deal with adversity

It is important to be able to deal with external pressures going on in your life such as conflicts related to family, peers, school, work, and relationships. Deal with and manage this discord before your match so you can maintain control of your emotions and can give 100% effort on the court.

Learn mental techniques

Many athletes may have difficulty teaching themselves cognitive skills and would benefit from a few sessions with a sports psychologist/psychiatrist to understand and learn the techniques. Once the tactics are understood and learned, players can apply them to training and ultimately to their tournament arsenal, allowing them to play to their ultimate potential.

References

1. Morgan WP. Selected psychological factors limiting performance: A mental health model. In Clarke DH and Eckert HM (eds.), Limits of Human Performance. Champaign, Ill.: Human Kinetics Publishers, 1985.

Dr. Cohen had a private practice in psychiatry for more than 35 years. He is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University in Philadelphia. Dr. Cohen has been a nationally ranked tennis player from age 12 to the present and served as captain of the tennis team at the University of Pennsylvania, Philadelphia. Dr. Cohen, who was ranked No. 1 in tennis in the middle states section and in the country in various categories and times, was inducted into the Philadelphia Jewish Sports Hall of Fame in 2012. Dr. Cohen has no conflicts of interest.

Ms. Cohen, Dr. Cohen’s daughter, was No. 1 ranked in the United States in junior tennis and No. 4 in the world. In addition, Ms. Cohen was ranked among the top 100 players in the world by the professional World Tennis Association. She also was the No. 2 college player in United States, and an All-American at the University of Miami. She holds a master’s in sports psychology, and presently works as a sports psychologist and tennis professional in Philadelphia. Ms. Cohen has no conflicts of interest.

Successful athletes exhibit positive mental health. This mental health is directly related to athletic success and high levels of performance.¹ Mental skills are as important as natural physical ability and mechanical skills in the sport of tennis.

Research has shown that tennis is 85% mental and that players spend 80% of their time on the court handling emotions. Some players look good in practice when they are not under pressure but cannot win matches (they have the physical skill level to win) because they cannot handle their own emotions during the duress of a match. They are affected by anger, fear, stress, poor concentration, and other internal elements that interfere with their ability to perform at an optimal level. Competitors may also be affected by external factors such as the sun, wind, an opponent, and so on, and may use these situations as an excuse not to win.

Players normally practice physical skills but rarely practice cognitive techniques. Regardless of level of play – pro, collegiate, junior, or club – practicing mental skills will greatly improve the players’ arsenal of weapons, giving them an edge in matches and making them the best players they can be. Mental health professionals also can use these strategies to help motivate athletes who compete in other sports – and in other competitive endeavors.

Visualization is the formation of a mental image of something of your choice. Visualization imagery techniques can be used by players to calm themselves before playing a match so their emotions are not wasted on trying to quiet the minds and quell stress. Implementing the following visualization techniques will reduce a player’s anxiety during the match, allowing the player to direct energy toward optimal mental and physical performance on the court.

In advance of a match, encourage the player to learn and analyze the opponent’s strengths and weaknesses by watching the opponent play and/or from asking others. The night before the scheduled match, get the player to imagine how they will play points against their competitor. Play into the opponents’ vulnerabilities or first play to their strengths to expose shortcomings and – then attack their weakness. For example, if an opponent has a weak backhand, first play to the opponent’s forehand and, when the opponent is vulnerable, go into his backhand to get a short or weak ball – and attack. The following are specific strategies that mental health professionals who work with athletes can use to help them perform optimally.
 

Using visualization, shadowing

Visualize the correct way to hit a tennis stroke and repeat it over and over in your mind. On a tennis court or where ever you have adequate space, shadow a stroke by using a racket and repetitively performing the actual stroke without hitting a ball. At home, practice relaxation and deep breathing techniques at night before going to sleep. Put yourself in a relaxed state and visualize repetitively striking the ball correctly. The next time you actually hit the stroke, you will produce a better shot.

Focusing on, staying in the here and now

The “here” means to focus on what is happening on your own court, not what is happening on the court next to you. Players may be affected by external factors, such as the sun, wind, and their opponent and may use these conditions or situations as an excuse if they do not win. Ignore background chatter and distractions, and be a horse with blinders. Be responsible for yourself and your own actions; manage what you can and realize that you cannot control the weather or actions of your opponent.

The “now” refers to staying present and focusing only on the current point. Do not think of past mistakes. If you are winning a match, do not think about celebrating while the match is still in play. If you are losing, do not start to write a script of excuses why you lost the match. Instead, just concentrate on the present, point by point. Focusing will allow you to understand what is true and important in the here and now. Focusing will help alleviate stress and better equip you to make quick decisions and be clear about your intended actions.
 

Set realistic and achievable goals

It is always good to have goals and dreams; however, you as a player must understand the realities of your current level of play. Know your level; don’t be grandiose and think you are able to beat Rafael Nadal. Having an unrealistic attitude will result in frustration and poor performance during a match. Instead, set achievable, and realistic short- and long-term goals for yourself, which will aid in your overall tennis development. After the match is over, reflect upon and evaluate the points – and your overall performance.

Don’t devalue yourself if you lose a match. Do not feel too low from a loss or too high from a win. When you have a match loss, use it as an opportunity to learn from your mistakes and to improve by working on your weaknesses in future practice until you feel confident enough to use your new skills in a tournament.
 

Stay positive

Do not tie up your self-esteem as a person with your match outcome; in otherwords, separate feelings of self-worth from your match results. Cultivate an optimistic attitude and talk positively to yourself, strive to improve, and maintain positive self-esteem in practice and in matches. During practice, allocate 110% effort, and focus on the process, not the outcome. Arrange your practice matches so that one-third of them are against players of your same level, one-third against players worse than you, and one-third against players better than yourself.

Deal with adversity

It is important to be able to deal with external pressures going on in your life such as conflicts related to family, peers, school, work, and relationships. Deal with and manage this discord before your match so you can maintain control of your emotions and can give 100% effort on the court.

Learn mental techniques

Many athletes may have difficulty teaching themselves cognitive skills and would benefit from a few sessions with a sports psychologist/psychiatrist to understand and learn the techniques. Once the tactics are understood and learned, players can apply them to training and ultimately to their tournament arsenal, allowing them to play to their ultimate potential.

References

1. Morgan WP. Selected psychological factors limiting performance: A mental health model. In Clarke DH and Eckert HM (eds.), Limits of Human Performance. Champaign, Ill.: Human Kinetics Publishers, 1985.

Dr. Cohen had a private practice in psychiatry for more than 35 years. He is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University in Philadelphia. Dr. Cohen has been a nationally ranked tennis player from age 12 to the present and served as captain of the tennis team at the University of Pennsylvania, Philadelphia. Dr. Cohen, who was ranked No. 1 in tennis in the middle states section and in the country in various categories and times, was inducted into the Philadelphia Jewish Sports Hall of Fame in 2012. Dr. Cohen has no conflicts of interest.

Ms. Cohen, Dr. Cohen’s daughter, was No. 1 ranked in the United States in junior tennis and No. 4 in the world. In addition, Ms. Cohen was ranked among the top 100 players in the world by the professional World Tennis Association. She also was the No. 2 college player in United States, and an All-American at the University of Miami. She holds a master’s in sports psychology, and presently works as a sports psychologist and tennis professional in Philadelphia. Ms. Cohen has no conflicts of interest.

Successful athletes exhibit positive mental health. This mental health is directly related to athletic success and high levels of performance.¹ Mental skills are as important as natural physical ability and mechanical skills in the sport of tennis.

Research has shown that tennis is 85% mental and that players spend 80% of their time on the court handling emotions. Some players look good in practice when they are not under pressure but cannot win matches (they have the physical skill level to win) because they cannot handle their own emotions during the duress of a match. They are affected by anger, fear, stress, poor concentration, and other internal elements that interfere with their ability to perform at an optimal level. Competitors may also be affected by external factors such as the sun, wind, an opponent, and so on, and may use these situations as an excuse not to win.

Players normally practice physical skills but rarely practice cognitive techniques. Regardless of level of play – pro, collegiate, junior, or club – practicing mental skills will greatly improve the players’ arsenal of weapons, giving them an edge in matches and making them the best players they can be. Mental health professionals also can use these strategies to help motivate athletes who compete in other sports – and in other competitive endeavors.

Visualization is the formation of a mental image of something of your choice. Visualization imagery techniques can be used by players to calm themselves before playing a match so their emotions are not wasted on trying to quiet the minds and quell stress. Implementing the following visualization techniques will reduce a player’s anxiety during the match, allowing the player to direct energy toward optimal mental and physical performance on the court.

In advance of a match, encourage the player to learn and analyze the opponent’s strengths and weaknesses by watching the opponent play and/or from asking others. The night before the scheduled match, get the player to imagine how they will play points against their competitor. Play into the opponents’ vulnerabilities or first play to their strengths to expose shortcomings and – then attack their weakness. For example, if an opponent has a weak backhand, first play to the opponent’s forehand and, when the opponent is vulnerable, go into his backhand to get a short or weak ball – and attack. The following are specific strategies that mental health professionals who work with athletes can use to help them perform optimally.
 

Using visualization, shadowing

Visualize the correct way to hit a tennis stroke and repeat it over and over in your mind. On a tennis court or where ever you have adequate space, shadow a stroke by using a racket and repetitively performing the actual stroke without hitting a ball. At home, practice relaxation and deep breathing techniques at night before going to sleep. Put yourself in a relaxed state and visualize repetitively striking the ball correctly. The next time you actually hit the stroke, you will produce a better shot.

Focusing on, staying in the here and now

The “here” means to focus on what is happening on your own court, not what is happening on the court next to you. Players may be affected by external factors, such as the sun, wind, and their opponent and may use these conditions or situations as an excuse if they do not win. Ignore background chatter and distractions, and be a horse with blinders. Be responsible for yourself and your own actions; manage what you can and realize that you cannot control the weather or actions of your opponent.

The “now” refers to staying present and focusing only on the current point. Do not think of past mistakes. If you are winning a match, do not think about celebrating while the match is still in play. If you are losing, do not start to write a script of excuses why you lost the match. Instead, just concentrate on the present, point by point. Focusing will allow you to understand what is true and important in the here and now. Focusing will help alleviate stress and better equip you to make quick decisions and be clear about your intended actions.
 

Set realistic and achievable goals

It is always good to have goals and dreams; however, you as a player must understand the realities of your current level of play. Know your level; don’t be grandiose and think you are able to beat Rafael Nadal. Having an unrealistic attitude will result in frustration and poor performance during a match. Instead, set achievable, and realistic short- and long-term goals for yourself, which will aid in your overall tennis development. After the match is over, reflect upon and evaluate the points – and your overall performance.

Don’t devalue yourself if you lose a match. Do not feel too low from a loss or too high from a win. When you have a match loss, use it as an opportunity to learn from your mistakes and to improve by working on your weaknesses in future practice until you feel confident enough to use your new skills in a tournament.
 

Stay positive

Do not tie up your self-esteem as a person with your match outcome; in otherwords, separate feelings of self-worth from your match results. Cultivate an optimistic attitude and talk positively to yourself, strive to improve, and maintain positive self-esteem in practice and in matches. During practice, allocate 110% effort, and focus on the process, not the outcome. Arrange your practice matches so that one-third of them are against players of your same level, one-third against players worse than you, and one-third against players better than yourself.

Deal with adversity

It is important to be able to deal with external pressures going on in your life such as conflicts related to family, peers, school, work, and relationships. Deal with and manage this discord before your match so you can maintain control of your emotions and can give 100% effort on the court.

Learn mental techniques

Many athletes may have difficulty teaching themselves cognitive skills and would benefit from a few sessions with a sports psychologist/psychiatrist to understand and learn the techniques. Once the tactics are understood and learned, players can apply them to training and ultimately to their tournament arsenal, allowing them to play to their ultimate potential.

References

1. Morgan WP. Selected psychological factors limiting performance: A mental health model. In Clarke DH and Eckert HM (eds.), Limits of Human Performance. Champaign, Ill.: Human Kinetics Publishers, 1985.

Dr. Cohen had a private practice in psychiatry for more than 35 years. He is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University in Philadelphia. Dr. Cohen has been a nationally ranked tennis player from age 12 to the present and served as captain of the tennis team at the University of Pennsylvania, Philadelphia. Dr. Cohen, who was ranked No. 1 in tennis in the middle states section and in the country in various categories and times, was inducted into the Philadelphia Jewish Sports Hall of Fame in 2012. Dr. Cohen has no conflicts of interest.

Ms. Cohen, Dr. Cohen’s daughter, was No. 1 ranked in the United States in junior tennis and No. 4 in the world. In addition, Ms. Cohen was ranked among the top 100 players in the world by the professional World Tennis Association. She also was the No. 2 college player in United States, and an All-American at the University of Miami. She holds a master’s in sports psychology, and presently works as a sports psychologist and tennis professional in Philadelphia. Ms. Cohen has no conflicts of interest.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

rfranki@mdedge.com

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

rfranki@mdedge.com

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

rfranki@mdedge.com

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

bjancin@mdedge.com

SOURCE: Ho R. ECNP 2020, Session ISE01.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

bjancin@mdedge.com

SOURCE: Ho R. ECNP 2020, Session ISE01.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

bjancin@mdedge.com

SOURCE: Ho R. ECNP 2020, Session ISE01.

Current and former users of e-cigarettes are more likely to report sleep deprivation, compared with those who have never used e-cigarettes, according to the first study to evaluate the association in a large, nationally representative population of young adults.

“The e-cigarette use and sleep deprivation association seems to have a dose-response nature as the point estimate of the association increased with increased exposure to e-cigarette,” Sina Kianersi, DVM, and associates at Indiana University, Bloomington, said in Addictive Behaviors.

Sleep deprivation was 49% more prevalent among everyday users of e-cigarettes, compared with nonusers. Prevalence ratios for former users (1.31) and occasional users (1.25) also showed significantly higher sleep deprivation, compared with nonusers, they reported based on a bivariate analysis of data from young adults aged 18-24 years who participated in the 2017 and 2018 Behavioral Risk Factor Surveillance System surveys.

After adjustment for multiple confounders, young adults who currently used e-cigarettes every day were 42% more likely to report sleep deprivation than those who never used e-cigarettes, a difference that was statistically significant. The prevalence of sleep deprivation among those who used e-cigarettes on some days was not significantly higher (prevalence ratio, 1.08), but the ratio between former users and never users was a significant 1.17, the investigators said.

“The nicotine in the inhaled e-cigarette aerosols may have negative effects on sleep architecture and disturb the neurotransmitters that regulate sleep cycle,” they suggested, and since higher doses of nicotine produce greater reductions in sleep duration, “those who use e-cigarette on a daily basis might consume higher doses of nicotine, compared to some days, former, and never users, and therefore get fewer hours of sleep.”

Nicotine withdrawal, on the other hand, has been found to increase sleep duration in a dose-dependent manner, which “could explain the smaller [prevalence ratios] observed for the association between e-cigarette use and sleep deprivation among former and some days e-cigarette users,” Dr. Kianersi and associates added.

The bivariate analysis involved 18,945 survey respondents, of whom 16,427 were included in the fully adjusted model using 12 confounding factors.

rfranki@mdedge.com

SOURCE: Kianersi S et al. Addict Behav. 2020 Sep 6. doi: 10.1016/j.addbeh.2020.106646.

Current and former users of e-cigarettes are more likely to report sleep deprivation, compared with those who have never used e-cigarettes, according to the first study to evaluate the association in a large, nationally representative population of young adults.

“The e-cigarette use and sleep deprivation association seems to have a dose-response nature as the point estimate of the association increased with increased exposure to e-cigarette,” Sina Kianersi, DVM, and associates at Indiana University, Bloomington, said in Addictive Behaviors.

Sleep deprivation was 49% more prevalent among everyday users of e-cigarettes, compared with nonusers. Prevalence ratios for former users (1.31) and occasional users (1.25) also showed significantly higher sleep deprivation, compared with nonusers, they reported based on a bivariate analysis of data from young adults aged 18-24 years who participated in the 2017 and 2018 Behavioral Risk Factor Surveillance System surveys.

After adjustment for multiple confounders, young adults who currently used e-cigarettes every day were 42% more likely to report sleep deprivation than those who never used e-cigarettes, a difference that was statistically significant. The prevalence of sleep deprivation among those who used e-cigarettes on some days was not significantly higher (prevalence ratio, 1.08), but the ratio between former users and never users was a significant 1.17, the investigators said.

“The nicotine in the inhaled e-cigarette aerosols may have negative effects on sleep architecture and disturb the neurotransmitters that regulate sleep cycle,” they suggested, and since higher doses of nicotine produce greater reductions in sleep duration, “those who use e-cigarette on a daily basis might consume higher doses of nicotine, compared to some days, former, and never users, and therefore get fewer hours of sleep.”

Nicotine withdrawal, on the other hand, has been found to increase sleep duration in a dose-dependent manner, which “could explain the smaller [prevalence ratios] observed for the association between e-cigarette use and sleep deprivation among former and some days e-cigarette users,” Dr. Kianersi and associates added.

The bivariate analysis involved 18,945 survey respondents, of whom 16,427 were included in the fully adjusted model using 12 confounding factors.

rfranki@mdedge.com

SOURCE: Kianersi S et al. Addict Behav. 2020 Sep 6. doi: 10.1016/j.addbeh.2020.106646.

Current and former users of e-cigarettes are more likely to report sleep deprivation, compared with those who have never used e-cigarettes, according to the first study to evaluate the association in a large, nationally representative population of young adults.

“The e-cigarette use and sleep deprivation association seems to have a dose-response nature as the point estimate of the association increased with increased exposure to e-cigarette,” Sina Kianersi, DVM, and associates at Indiana University, Bloomington, said in Addictive Behaviors.

Sleep deprivation was 49% more prevalent among everyday users of e-cigarettes, compared with nonusers. Prevalence ratios for former users (1.31) and occasional users (1.25) also showed significantly higher sleep deprivation, compared with nonusers, they reported based on a bivariate analysis of data from young adults aged 18-24 years who participated in the 2017 and 2018 Behavioral Risk Factor Surveillance System surveys.

After adjustment for multiple confounders, young adults who currently used e-cigarettes every day were 42% more likely to report sleep deprivation than those who never used e-cigarettes, a difference that was statistically significant. The prevalence of sleep deprivation among those who used e-cigarettes on some days was not significantly higher (prevalence ratio, 1.08), but the ratio between former users and never users was a significant 1.17, the investigators said.

“The nicotine in the inhaled e-cigarette aerosols may have negative effects on sleep architecture and disturb the neurotransmitters that regulate sleep cycle,” they suggested, and since higher doses of nicotine produce greater reductions in sleep duration, “those who use e-cigarette on a daily basis might consume higher doses of nicotine, compared to some days, former, and never users, and therefore get fewer hours of sleep.”

Nicotine withdrawal, on the other hand, has been found to increase sleep duration in a dose-dependent manner, which “could explain the smaller [prevalence ratios] observed for the association between e-cigarette use and sleep deprivation among former and some days e-cigarette users,” Dr. Kianersi and associates added.

The bivariate analysis involved 18,945 survey respondents, of whom 16,427 were included in the fully adjusted model using 12 confounding factors.

rfranki@mdedge.com

SOURCE: Kianersi S et al. Addict Behav. 2020 Sep 6. doi: 10.1016/j.addbeh.2020.106646.

While anxiety was at the top of my list of emotional states that generated office visits in my pediatric practice, depression always ran a close second. Not infrequently, patients would report symptoms that suggested they were harboring both morbidities.

LumineImages/iStock/Getty Images

Although some families appear to be prone to depression, I’m not aware that a definable genetic basis has been discovered. Like me, you may have wondered what factors determine whether an individual will become depressed or merely be unhappy when things aren’t going well. We all have known people who have weathered disappointment and life-altering calamities without even a hint of being depressed. On the other hand you probably have met numerous patients and acquaintances who have become significantly depressed as the result of simply worrying that some disaster might befall them.

Is this variable vulnerability to depression the result of some as yet undiscovered neurotransmitter? Or are there certain lifestyle features that make individuals more prone to depression? Or ... could it be both? In other words are there behaviors that can tweak a person’s telomeres in such a way that triggers a biochemical cascade that results in depression?

A recent paper in the American Journal of Psychiatry doesn’t drill down through the genetic and biochemical strata, but it does suggest that there are “modifiable” behaviors that may contribute to depression. The researchers based at Harvard Medical School in Boston accessed a database of more than 100,000 adults in the United Kingdom. With use of a two-stage method that included a strategy similar to that employed for identifying genetic risk factors for disease, the researchers scanned a large number of factors that they considered modifiable, searching for those that might be associated with the development of depression.

Not surprisingly, they discovered that those respondents who more frequently confided in others and more frequently visited with family and friends were less likely to become depressed. Of course, this protective effect of social connection can cut both ways during the pandemic. During this pandemic if those people you confide in are not currently in your “bubble,” you may have a problem. This may explain why, despite warnings of their dangers, bars continue to be so attractive. It’s probably not just the alcohol but it’s the bartenders and patrons who are willing to listen that patrons seek out. It would be helpful if more people felt comfortable sharing their feelings with members of their family bubble. But you and I know that many families don’t come even close to matching the Brady Bunch image of a functionality.

Somewhat surprisingly to the Harvard researchers was their finding that time watching television also was a significant risk factor for the development of depression. Their data did not allow them to determine whether this observation was linked to the sedentary nature of television watching or the content of the shows being viewed. I suspect that content is not the problem. But in addition to being a sedentary activity, television watching often is isolating. When television was first introduced to the mass market, families grouped around the household’s lone set, much as families did back when radios became popular. In their infancy radio listening and television viewing were social activities rich with discussion and shared emotions.

However, as televisions became less expensive and no longer required large pieces of furniture to house them, television viewing became a more solitary and individual activity. Televisions became obligatory furnishings of every bedroom, and parents and children could withdraw to their own spaces and be entertained free of any opportunity or obligation to interact with the rest of family.

This new research into the risk factors for depression suggests that again we should be strongly discouraging parents from allowing their children to have a television or electronic viewing device in their bedrooms without any way of monitoring their usage. At least among children, television watching should be a modifiable behavior.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

While anxiety was at the top of my list of emotional states that generated office visits in my pediatric practice, depression always ran a close second. Not infrequently, patients would report symptoms that suggested they were harboring both morbidities.

LumineImages/iStock/Getty Images

Although some families appear to be prone to depression, I’m not aware that a definable genetic basis has been discovered. Like me, you may have wondered what factors determine whether an individual will become depressed or merely be unhappy when things aren’t going well. We all have known people who have weathered disappointment and life-altering calamities without even a hint of being depressed. On the other hand you probably have met numerous patients and acquaintances who have become significantly depressed as the result of simply worrying that some disaster might befall them.

Is this variable vulnerability to depression the result of some as yet undiscovered neurotransmitter? Or are there certain lifestyle features that make individuals more prone to depression? Or ... could it be both? In other words are there behaviors that can tweak a person’s telomeres in such a way that triggers a biochemical cascade that results in depression?

A recent paper in the American Journal of Psychiatry doesn’t drill down through the genetic and biochemical strata, but it does suggest that there are “modifiable” behaviors that may contribute to depression. The researchers based at Harvard Medical School in Boston accessed a database of more than 100,000 adults in the United Kingdom. With use of a two-stage method that included a strategy similar to that employed for identifying genetic risk factors for disease, the researchers scanned a large number of factors that they considered modifiable, searching for those that might be associated with the development of depression.

Not surprisingly, they discovered that those respondents who more frequently confided in others and more frequently visited with family and friends were less likely to become depressed. Of course, this protective effect of social connection can cut both ways during the pandemic. During this pandemic if those people you confide in are not currently in your “bubble,” you may have a problem. This may explain why, despite warnings of their dangers, bars continue to be so attractive. It’s probably not just the alcohol but it’s the bartenders and patrons who are willing to listen that patrons seek out. It would be helpful if more people felt comfortable sharing their feelings with members of their family bubble. But you and I know that many families don’t come even close to matching the Brady Bunch image of a functionality.

Somewhat surprisingly to the Harvard researchers was their finding that time watching television also was a significant risk factor for the development of depression. Their data did not allow them to determine whether this observation was linked to the sedentary nature of television watching or the content of the shows being viewed. I suspect that content is not the problem. But in addition to being a sedentary activity, television watching often is isolating. When television was first introduced to the mass market, families grouped around the household’s lone set, much as families did back when radios became popular. In their infancy radio listening and television viewing were social activities rich with discussion and shared emotions.

However, as televisions became less expensive and no longer required large pieces of furniture to house them, television viewing became a more solitary and individual activity. Televisions became obligatory furnishings of every bedroom, and parents and children could withdraw to their own spaces and be entertained free of any opportunity or obligation to interact with the rest of family.

This new research into the risk factors for depression suggests that again we should be strongly discouraging parents from allowing their children to have a television or electronic viewing device in their bedrooms without any way of monitoring their usage. At least among children, television watching should be a modifiable behavior.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

While anxiety was at the top of my list of emotional states that generated office visits in my pediatric practice, depression always ran a close second. Not infrequently, patients would report symptoms that suggested they were harboring both morbidities.

LumineImages/iStock/Getty Images

Although some families appear to be prone to depression, I’m not aware that a definable genetic basis has been discovered. Like me, you may have wondered what factors determine whether an individual will become depressed or merely be unhappy when things aren’t going well. We all have known people who have weathered disappointment and life-altering calamities without even a hint of being depressed. On the other hand you probably have met numerous patients and acquaintances who have become significantly depressed as the result of simply worrying that some disaster might befall them.

Is this variable vulnerability to depression the result of some as yet undiscovered neurotransmitter? Or are there certain lifestyle features that make individuals more prone to depression? Or ... could it be both? In other words are there behaviors that can tweak a person’s telomeres in such a way that triggers a biochemical cascade that results in depression?

A recent paper in the American Journal of Psychiatry doesn’t drill down through the genetic and biochemical strata, but it does suggest that there are “modifiable” behaviors that may contribute to depression. The researchers based at Harvard Medical School in Boston accessed a database of more than 100,000 adults in the United Kingdom. With use of a two-stage method that included a strategy similar to that employed for identifying genetic risk factors for disease, the researchers scanned a large number of factors that they considered modifiable, searching for those that might be associated with the development of depression.

Not surprisingly, they discovered that those respondents who more frequently confided in others and more frequently visited with family and friends were less likely to become depressed. Of course, this protective effect of social connection can cut both ways during the pandemic. During this pandemic if those people you confide in are not currently in your “bubble,” you may have a problem. This may explain why, despite warnings of their dangers, bars continue to be so attractive. It’s probably not just the alcohol but it’s the bartenders and patrons who are willing to listen that patrons seek out. It would be helpful if more people felt comfortable sharing their feelings with members of their family bubble. But you and I know that many families don’t come even close to matching the Brady Bunch image of a functionality.

Somewhat surprisingly to the Harvard researchers was their finding that time watching television also was a significant risk factor for the development of depression. Their data did not allow them to determine whether this observation was linked to the sedentary nature of television watching or the content of the shows being viewed. I suspect that content is not the problem. But in addition to being a sedentary activity, television watching often is isolating. When television was first introduced to the mass market, families grouped around the household’s lone set, much as families did back when radios became popular. In their infancy radio listening and television viewing were social activities rich with discussion and shared emotions.

However, as televisions became less expensive and no longer required large pieces of furniture to house them, television viewing became a more solitary and individual activity. Televisions became obligatory furnishings of every bedroom, and parents and children could withdraw to their own spaces and be entertained free of any opportunity or obligation to interact with the rest of family.

This new research into the risk factors for depression suggests that again we should be strongly discouraging parents from allowing their children to have a television or electronic viewing device in their bedrooms without any way of monitoring their usage. At least among children, television watching should be a modifiable behavior.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Using Telehealth to Improve Outcomes in Veterans at Risk for Suicide

The investigators will randomize 120 veterans in this 3-site trial over 16 months. Eligible veterans will include those to be discharged for a hospitalization for suicidal ideation. Baseline data collection and randomization will occur at discharge. The 3-month intervention will have study assessments at 2, 4, 8, and 12 weeks postdischarge. The study’s primary outcome measure is suicidal ideation (measured with the Beck Scale for Suicidal Ideation (BSS) and secondarily with the Columbia Scale for Suicidality (C-SSRS).

ID: NCT03724370
Sponsor: VA Pittsburgh Healthcare System
Contact: Gretchen Haas, PhD, gretchen.haas@va.gov; Crystal Spotts, MEd, crystal.spotts@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; VA NY Harbor Healthcare System, Manhattan Campus; VA Pittsburgh Healthcare System, Pennsylvania

Group (“Project Life Force”) vs. Individual Suicide Safety Planning RCT

The management of suicide risk is a pressing national public health issue especially among veterans. This grant consists of 2 arms: the novel treatment and treatment-as-usual. “Project Life Force” (PLF), a novel suicide safety planning group intervention has been developed to provide a mechanism to develop and enhance the Suicide Safety Plan (SSP) over time. PLF, a 10-session, group intervention, combines cognitive behavior therapy (CBT)/dialectical behavior therapy (DBT) skill-based, and psychoeducational approaches, to maximize suicide safety planning development and implementation. Veterans revise their plans over several weeks while learning coping, emotion regulation, and interpersonal skills to incorporate into their safety plans.

ID: NCT03653637
Sponsor: VA Office of Research and Development
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

SAFER: A Brief Intervention Involving Family Members in Suicide Safety Planning (SAFER)

The management of suicide risk is a pressing national public health issue especially among veterans, and there exist no guidelines of how best to involve family members in this effort. This proposal will integrate family and couples communication skills training with suicide safety planning. The goal is for the sharing of veteran suicide safety plans with family members and the construction of a parallel family member safety plan, in efforts to mobilize and support family involvement.

ID: NCT03034863
Sponsor: VA Office of Research and Development
Contact: Marianne Goodman, MD, marianne.goodman@va.gov
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Location: James J. Peters Medical Center, Bronx, New York

Suicide and Trauma Reduction Initiative Among Veterans (STRIVE)

The present study is a pragmatic clinical trial that will examine the effectiveness of Cognitive Processing Therapy (CPT) in reducing PTSD symptom severity, depression symptoms, and suicidal thoughts among military personnel and veterans with PTSD when delivered in 3 different formats: (1) 12 sessions delivered once per week in an office/clinic setting; (2) 12 sessions delivered once per day in an office/clinic setting; and (3) 12 sessions delivered once per day in a recreational setting.

ID: NCT03933059
Sponsor: University of Utah
Contact: Craig Bryan, PhD, ABPP, and Feea Leifker, PhD, MPH, ncvs@utah.edu
Locations: University of Utah, Salt Lake City

CAMS-G Group Therapy for Suicidal Veterans

The primary aim of this pilot study is to determine the feasibility and acceptability of CAMS-G. Our aim is to determine if CAMS-G is an effective treatment and whether it has the potential to be tested in a large-scale setting.

ID: NCT03682406
Sponsor: Louisville VA Medical Center
Contact: Lora Johnson, PhD, lora.johnson2@va.gov; Stephen O’Connor, PhD, stephen.oconnor@louisville.edu
Location: Robley Rex VA Medical Center, Louisville, Kentucky

RCT of Brief CBT-I in Primary Care Veterans With Suicidal Thoughts

There is a strong association between insomnia and suicidal thoughts and behaviors. Insomnia also frequently co-occurs with other common conditions associated with suicide such as depression and posttraumatic stress disorder. This project focuses on improving sleep as a novel suicide prevention strategy that can be delivered to a broad range of veterans. The study will examine how cognitive behavioral therapy for insomnia, an efficacious treatment for insomnia, may reduce suicidal thoughts in veterans who also suffer from co-occurring conditions when delivered by integrated primary care clinicians.

ID: NCT03603717
Sponsor: VA Office of Research and Development
Contact: Wilfred Pigeon, PhD, wilfred.pigeon2@va.gov; Jennifer Funderburk, PhD, jennifer.funderburk@va.gov
Locations: VA Western New York Healthcare System, Buffalo; Canandaigua VA Medical Center, New York; Syracuse VA Medical Center, New York

 

 

Intranasal Ketamine for Suicidal Ideation in Veterans

To address the significant need for effective treatment of suicidal ideation in veterans, this trial is designed as an open label pilot study of intranasal ketamine in 15 people.

ID: NCT03788694
Sponsor: Bronx Veterans Medical Research Foundation, Inc
Contact: Rachel Harris, MA, rachel.harris6@va.gov; Marianne Goodman, MD, marianne.goodman@va.gov
Location: James J. Peters VA Medical Center, Bronx, New York

Couples Intervention to Improve Mental Health

Over the last decade, suicide rates have risen within the military and have remained high. Converging evidence suggests that suicide prevention efforts may be enhanced by explicitly including family members in treatment. The study’s objectives are to test the effect of the CCRP, a targeted single session couples intervention on suicide ideation among military service members and veterans, and to understand how the use of the CCRP impacts suicide risk during the 6 months immediately postdischarge from a psychiatric inpatient unit.

ID: NCT04084756
Sponsor: Wesleyan University
Contact: Alexis May, PhD, amay01@wesleyan.edu
Location: Salt Lake Behavioral Health, Utah

Clinical and Imaging Trial of Uridine for Veterans With Suicidal Ideation

This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for suicidal ideation in veterans. The investigators hypothesize that the administration of a naturally occurring dietary supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this study is to determine whether 4 weeks of uridine supplementation is an effective treatment for suicidal ideation in veterans, when compared to a group taking a placebo.

ID: NCT03265964
Sponsor: VA Office of Research and Development
Contact: Douglas G Kondo, MD, douglas.kondo@va.gov; Danielle Boxer, MS, danielle.boxer@utah.edu
Location: VA Salt Lake City Health Care System, Utah

Multisite RCT of STEP-Home: A Transdiagnostic Skill-based Community Reintegration Workshop (by invitation)

In this proposal, the investigators extend their previous SPiRE feasibility and preliminary effectiveness study to examine STEP-Home efficacy in a RCT design. This novel therapy will target the specific needs of a broad range of underserved post-9/11 veterans. It is designed to foster reintegration by facilitating meaningful improvement in the functional skills most central to community participation: emotional regulation (ER), problem solving (PS), and attention functioning (AT). The skills trained in the STEP-Home workshop are novel in their collective use and have not been systematically applied to a veteran population prior to the investigators’ SPiRE study. STEP-Home will equip veterans with skills to improve daily function, reduce anger and irritability, and assist reintegration to civilian life through return to work, family, and community, while simultaneously providing psychoeducation to promote future engagement in VA care.

ID: NCT03868930
Sponsor: VA Office of Research and Development
Locations: VA Boston Healthcare System, Jamaica Plain Campus, Massachusetts; Michael E. DeBakey VA Medical Center, Houston, Texas

The AIM Study: Investigating Whether Actigraphy and Ideation Measures Can Promote Patient Safety

This is a research project looking at whether measuring movements or responses to certain questions can help predict suicidal thoughts or actions. This project has 2 parts: The first part will occur while the participant is receiving hospitalized at the Bedford VA Hospital. It involves wearing a watch-like device on his/her wrist and answering questions or doing tasks to measure mood and other mental health symptoms, and suicidal thoughts. In the second phase, the investigators will call the participant around 12 months after s/he has left the hospital. The investigators will discuss how s/he is doing and if s/he has had suicidal thoughts or made suicidal acts.

ID: NCT03080168
Sponsor: VA Office of Research and Development
Contact: Eric G Smith, MD PhD MPH, eric.smith5@va.gov
Location: Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts

Using Telehealth to Improve Outcomes in Veterans at Risk for Suicide

The investigators will randomize 120 veterans in this 3-site trial over 16 months. Eligible veterans will include those to be discharged for a hospitalization for suicidal ideation. Baseline data collection and randomization will occur at discharge. The 3-month intervention will have study assessments at 2, 4, 8, and 12 weeks postdischarge. The study’s primary outcome measure is suicidal ideation (measured with the Beck Scale for Suicidal Ideation (BSS) and secondarily with the Columbia Scale for Suicidality (C-SSRS).

ID: NCT03724370
Sponsor: VA Pittsburgh Healthcare System
Contact: Gretchen Haas, PhD, gretchen.haas@va.gov; Crystal Spotts, MEd, crystal.spotts@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; VA NY Harbor Healthcare System, Manhattan Campus; VA Pittsburgh Healthcare System, Pennsylvania

Group (“Project Life Force”) vs. Individual Suicide Safety Planning RCT

The management of suicide risk is a pressing national public health issue especially among veterans. This grant consists of 2 arms: the novel treatment and treatment-as-usual. “Project Life Force” (PLF), a novel suicide safety planning group intervention has been developed to provide a mechanism to develop and enhance the Suicide Safety Plan (SSP) over time. PLF, a 10-session, group intervention, combines cognitive behavior therapy (CBT)/dialectical behavior therapy (DBT) skill-based, and psychoeducational approaches, to maximize suicide safety planning development and implementation. Veterans revise their plans over several weeks while learning coping, emotion regulation, and interpersonal skills to incorporate into their safety plans.

ID: NCT03653637
Sponsor: VA Office of Research and Development
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

SAFER: A Brief Intervention Involving Family Members in Suicide Safety Planning (SAFER)

The management of suicide risk is a pressing national public health issue especially among veterans, and there exist no guidelines of how best to involve family members in this effort. This proposal will integrate family and couples communication skills training with suicide safety planning. The goal is for the sharing of veteran suicide safety plans with family members and the construction of a parallel family member safety plan, in efforts to mobilize and support family involvement.

ID: NCT03034863
Sponsor: VA Office of Research and Development
Contact: Marianne Goodman, MD, marianne.goodman@va.gov
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Location: James J. Peters Medical Center, Bronx, New York

Suicide and Trauma Reduction Initiative Among Veterans (STRIVE)

The present study is a pragmatic clinical trial that will examine the effectiveness of Cognitive Processing Therapy (CPT) in reducing PTSD symptom severity, depression symptoms, and suicidal thoughts among military personnel and veterans with PTSD when delivered in 3 different formats: (1) 12 sessions delivered once per week in an office/clinic setting; (2) 12 sessions delivered once per day in an office/clinic setting; and (3) 12 sessions delivered once per day in a recreational setting.

ID: NCT03933059
Sponsor: University of Utah
Contact: Craig Bryan, PhD, ABPP, and Feea Leifker, PhD, MPH, ncvs@utah.edu
Locations: University of Utah, Salt Lake City

CAMS-G Group Therapy for Suicidal Veterans

The primary aim of this pilot study is to determine the feasibility and acceptability of CAMS-G. Our aim is to determine if CAMS-G is an effective treatment and whether it has the potential to be tested in a large-scale setting.

ID: NCT03682406
Sponsor: Louisville VA Medical Center
Contact: Lora Johnson, PhD, lora.johnson2@va.gov; Stephen O’Connor, PhD, stephen.oconnor@louisville.edu
Location: Robley Rex VA Medical Center, Louisville, Kentucky

RCT of Brief CBT-I in Primary Care Veterans With Suicidal Thoughts

There is a strong association between insomnia and suicidal thoughts and behaviors. Insomnia also frequently co-occurs with other common conditions associated with suicide such as depression and posttraumatic stress disorder. This project focuses on improving sleep as a novel suicide prevention strategy that can be delivered to a broad range of veterans. The study will examine how cognitive behavioral therapy for insomnia, an efficacious treatment for insomnia, may reduce suicidal thoughts in veterans who also suffer from co-occurring conditions when delivered by integrated primary care clinicians.

ID: NCT03603717
Sponsor: VA Office of Research and Development
Contact: Wilfred Pigeon, PhD, wilfred.pigeon2@va.gov; Jennifer Funderburk, PhD, jennifer.funderburk@va.gov
Locations: VA Western New York Healthcare System, Buffalo; Canandaigua VA Medical Center, New York; Syracuse VA Medical Center, New York

 

 

Intranasal Ketamine for Suicidal Ideation in Veterans

To address the significant need for effective treatment of suicidal ideation in veterans, this trial is designed as an open label pilot study of intranasal ketamine in 15 people.

ID: NCT03788694
Sponsor: Bronx Veterans Medical Research Foundation, Inc
Contact: Rachel Harris, MA, rachel.harris6@va.gov; Marianne Goodman, MD, marianne.goodman@va.gov
Location: James J. Peters VA Medical Center, Bronx, New York

Couples Intervention to Improve Mental Health

Over the last decade, suicide rates have risen within the military and have remained high. Converging evidence suggests that suicide prevention efforts may be enhanced by explicitly including family members in treatment. The study’s objectives are to test the effect of the CCRP, a targeted single session couples intervention on suicide ideation among military service members and veterans, and to understand how the use of the CCRP impacts suicide risk during the 6 months immediately postdischarge from a psychiatric inpatient unit.

ID: NCT04084756
Sponsor: Wesleyan University
Contact: Alexis May, PhD, amay01@wesleyan.edu
Location: Salt Lake Behavioral Health, Utah

Clinical and Imaging Trial of Uridine for Veterans With Suicidal Ideation

This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for suicidal ideation in veterans. The investigators hypothesize that the administration of a naturally occurring dietary supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this study is to determine whether 4 weeks of uridine supplementation is an effective treatment for suicidal ideation in veterans, when compared to a group taking a placebo.

ID: NCT03265964
Sponsor: VA Office of Research and Development
Contact: Douglas G Kondo, MD, douglas.kondo@va.gov; Danielle Boxer, MS, danielle.boxer@utah.edu
Location: VA Salt Lake City Health Care System, Utah

Multisite RCT of STEP-Home: A Transdiagnostic Skill-based Community Reintegration Workshop (by invitation)

In this proposal, the investigators extend their previous SPiRE feasibility and preliminary effectiveness study to examine STEP-Home efficacy in a RCT design. This novel therapy will target the specific needs of a broad range of underserved post-9/11 veterans. It is designed to foster reintegration by facilitating meaningful improvement in the functional skills most central to community participation: emotional regulation (ER), problem solving (PS), and attention functioning (AT). The skills trained in the STEP-Home workshop are novel in their collective use and have not been systematically applied to a veteran population prior to the investigators’ SPiRE study. STEP-Home will equip veterans with skills to improve daily function, reduce anger and irritability, and assist reintegration to civilian life through return to work, family, and community, while simultaneously providing psychoeducation to promote future engagement in VA care.

ID: NCT03868930
Sponsor: VA Office of Research and Development
Locations: VA Boston Healthcare System, Jamaica Plain Campus, Massachusetts; Michael E. DeBakey VA Medical Center, Houston, Texas

The AIM Study: Investigating Whether Actigraphy and Ideation Measures Can Promote Patient Safety

This is a research project looking at whether measuring movements or responses to certain questions can help predict suicidal thoughts or actions. This project has 2 parts: The first part will occur while the participant is receiving hospitalized at the Bedford VA Hospital. It involves wearing a watch-like device on his/her wrist and answering questions or doing tasks to measure mood and other mental health symptoms, and suicidal thoughts. In the second phase, the investigators will call the participant around 12 months after s/he has left the hospital. The investigators will discuss how s/he is doing and if s/he has had suicidal thoughts or made suicidal acts.

ID: NCT03080168
Sponsor: VA Office of Research and Development
Contact: Eric G Smith, MD PhD MPH, eric.smith5@va.gov
Location: Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts

Using Telehealth to Improve Outcomes in Veterans at Risk for Suicide

The investigators will randomize 120 veterans in this 3-site trial over 16 months. Eligible veterans will include those to be discharged for a hospitalization for suicidal ideation. Baseline data collection and randomization will occur at discharge. The 3-month intervention will have study assessments at 2, 4, 8, and 12 weeks postdischarge. The study’s primary outcome measure is suicidal ideation (measured with the Beck Scale for Suicidal Ideation (BSS) and secondarily with the Columbia Scale for Suicidality (C-SSRS).

ID: NCT03724370
Sponsor: VA Pittsburgh Healthcare System
Contact: Gretchen Haas, PhD, gretchen.haas@va.gov; Crystal Spotts, MEd, crystal.spotts@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; VA NY Harbor Healthcare System, Manhattan Campus; VA Pittsburgh Healthcare System, Pennsylvania

Group (“Project Life Force”) vs. Individual Suicide Safety Planning RCT

The management of suicide risk is a pressing national public health issue especially among veterans. This grant consists of 2 arms: the novel treatment and treatment-as-usual. “Project Life Force” (PLF), a novel suicide safety planning group intervention has been developed to provide a mechanism to develop and enhance the Suicide Safety Plan (SSP) over time. PLF, a 10-session, group intervention, combines cognitive behavior therapy (CBT)/dialectical behavior therapy (DBT) skill-based, and psychoeducational approaches, to maximize suicide safety planning development and implementation. Veterans revise their plans over several weeks while learning coping, emotion regulation, and interpersonal skills to incorporate into their safety plans.

ID: NCT03653637
Sponsor: VA Office of Research and Development
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Locations: James J. Peters Medical Center, Bronx, New York; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

SAFER: A Brief Intervention Involving Family Members in Suicide Safety Planning (SAFER)

The management of suicide risk is a pressing national public health issue especially among veterans, and there exist no guidelines of how best to involve family members in this effort. This proposal will integrate family and couples communication skills training with suicide safety planning. The goal is for the sharing of veteran suicide safety plans with family members and the construction of a parallel family member safety plan, in efforts to mobilize and support family involvement.

ID: NCT03034863
Sponsor: VA Office of Research and Development
Contact: Marianne Goodman, MD, marianne.goodman@va.gov
Contact: Sarah R Sullivan, sarah.sullivan@va.gov
Location: James J. Peters Medical Center, Bronx, New York

Suicide and Trauma Reduction Initiative Among Veterans (STRIVE)

The present study is a pragmatic clinical trial that will examine the effectiveness of Cognitive Processing Therapy (CPT) in reducing PTSD symptom severity, depression symptoms, and suicidal thoughts among military personnel and veterans with PTSD when delivered in 3 different formats: (1) 12 sessions delivered once per week in an office/clinic setting; (2) 12 sessions delivered once per day in an office/clinic setting; and (3) 12 sessions delivered once per day in a recreational setting.

ID: NCT03933059
Sponsor: University of Utah
Contact: Craig Bryan, PhD, ABPP, and Feea Leifker, PhD, MPH, ncvs@utah.edu
Locations: University of Utah, Salt Lake City

CAMS-G Group Therapy for Suicidal Veterans

The primary aim of this pilot study is to determine the feasibility and acceptability of CAMS-G. Our aim is to determine if CAMS-G is an effective treatment and whether it has the potential to be tested in a large-scale setting.

ID: NCT03682406
Sponsor: Louisville VA Medical Center
Contact: Lora Johnson, PhD, lora.johnson2@va.gov; Stephen O’Connor, PhD, stephen.oconnor@louisville.edu
Location: Robley Rex VA Medical Center, Louisville, Kentucky

RCT of Brief CBT-I in Primary Care Veterans With Suicidal Thoughts

There is a strong association between insomnia and suicidal thoughts and behaviors. Insomnia also frequently co-occurs with other common conditions associated with suicide such as depression and posttraumatic stress disorder. This project focuses on improving sleep as a novel suicide prevention strategy that can be delivered to a broad range of veterans. The study will examine how cognitive behavioral therapy for insomnia, an efficacious treatment for insomnia, may reduce suicidal thoughts in veterans who also suffer from co-occurring conditions when delivered by integrated primary care clinicians.

ID: NCT03603717
Sponsor: VA Office of Research and Development
Contact: Wilfred Pigeon, PhD, wilfred.pigeon2@va.gov; Jennifer Funderburk, PhD, jennifer.funderburk@va.gov
Locations: VA Western New York Healthcare System, Buffalo; Canandaigua VA Medical Center, New York; Syracuse VA Medical Center, New York

 

 

Intranasal Ketamine for Suicidal Ideation in Veterans

To address the significant need for effective treatment of suicidal ideation in veterans, this trial is designed as an open label pilot study of intranasal ketamine in 15 people.

ID: NCT03788694
Sponsor: Bronx Veterans Medical Research Foundation, Inc
Contact: Rachel Harris, MA, rachel.harris6@va.gov; Marianne Goodman, MD, marianne.goodman@va.gov
Location: James J. Peters VA Medical Center, Bronx, New York

Couples Intervention to Improve Mental Health

Over the last decade, suicide rates have risen within the military and have remained high. Converging evidence suggests that suicide prevention efforts may be enhanced by explicitly including family members in treatment. The study’s objectives are to test the effect of the CCRP, a targeted single session couples intervention on suicide ideation among military service members and veterans, and to understand how the use of the CCRP impacts suicide risk during the 6 months immediately postdischarge from a psychiatric inpatient unit.

ID: NCT04084756
Sponsor: Wesleyan University
Contact: Alexis May, PhD, amay01@wesleyan.edu
Location: Salt Lake Behavioral Health, Utah

Clinical and Imaging Trial of Uridine for Veterans With Suicidal Ideation

This is a randomized, double-blind, placebo-controlled study of the investigational drug uridine as a treatment for suicidal ideation in veterans. The investigators hypothesize that the administration of a naturally occurring dietary supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this study is to determine whether 4 weeks of uridine supplementation is an effective treatment for suicidal ideation in veterans, when compared to a group taking a placebo.

ID: NCT03265964
Sponsor: VA Office of Research and Development
Contact: Douglas G Kondo, MD, douglas.kondo@va.gov; Danielle Boxer, MS, danielle.boxer@utah.edu
Location: VA Salt Lake City Health Care System, Utah

Multisite RCT of STEP-Home: A Transdiagnostic Skill-based Community Reintegration Workshop (by invitation)

In this proposal, the investigators extend their previous SPiRE feasibility and preliminary effectiveness study to examine STEP-Home efficacy in a RCT design. This novel therapy will target the specific needs of a broad range of underserved post-9/11 veterans. It is designed to foster reintegration by facilitating meaningful improvement in the functional skills most central to community participation: emotional regulation (ER), problem solving (PS), and attention functioning (AT). The skills trained in the STEP-Home workshop are novel in their collective use and have not been systematically applied to a veteran population prior to the investigators’ SPiRE study. STEP-Home will equip veterans with skills to improve daily function, reduce anger and irritability, and assist reintegration to civilian life through return to work, family, and community, while simultaneously providing psychoeducation to promote future engagement in VA care.

ID: NCT03868930
Sponsor: VA Office of Research and Development
Locations: VA Boston Healthcare System, Jamaica Plain Campus, Massachusetts; Michael E. DeBakey VA Medical Center, Houston, Texas

The AIM Study: Investigating Whether Actigraphy and Ideation Measures Can Promote Patient Safety

This is a research project looking at whether measuring movements or responses to certain questions can help predict suicidal thoughts or actions. This project has 2 parts: The first part will occur while the participant is receiving hospitalized at the Bedford VA Hospital. It involves wearing a watch-like device on his/her wrist and answering questions or doing tasks to measure mood and other mental health symptoms, and suicidal thoughts. In the second phase, the investigators will call the participant around 12 months after s/he has left the hospital. The investigators will discuss how s/he is doing and if s/he has had suicidal thoughts or made suicidal acts.

ID: NCT03080168
Sponsor: VA Office of Research and Development
Contact: Eric G Smith, MD PhD MPH, eric.smith5@va.gov
Location: Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts

Although about 8.3% of the general adult civilian population will be diagnosed with posttraumatic stress disorder (PTSD) in their lifetime, rates of PTSD are even higher in the veteran population.^1,2 PTSD is associated with a number of psychosocial consequences in veterans, including decreased intimate partner relationship functioning.^3,4 For example, Cloitre and colleagues reported that PTSD is associated with difficulty with socializing, intimacy, responsibility, and control, all of which increase difficulties in intimate partner relationships.⁵ Similarly, researchers also have noted that traumatic experiences can affect an individual’s attachment style, resulting in progressive avoidance of interpersonal relationships, which can lead to marked difficulties in maintaining and beginning intimate partner relationships.^6,7 Despite these known consequences of PTSD, as Dekel and Monson noted in a review,further research is still needed regarding the mechanisms by which trauma and PTSD result in decreased intimate partner relationship functioning among veterans.⁸ Nonetheless, as positive interpersonal relationships are associated with decreased PTSD symptom severity^9,10 and increased engagement in PTSD treatment,¹¹ determining methods of measuring intimate partner relationship functioning in veterans with PTSD is important to inform future research and aid the provision of care.

To date, limited research has examined the valid measurement of intimate partner relationship functioning among veterans with PTSD. Many existing measures that comprehensively assess intimate partner relationship functioning are time and resource intensive. One such measure, the Timberlawn Couple and Family Evaluation Scales (TCFES), comprehensively assesses multiple pertinent domains of intimate partner relationship functioning (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict).¹² By assessing multiple domains, the TCFES offers a method of understanding the specific components of an individual’s intimate partner relationship in need of increased clinical attention.¹² However, the TCFES is a time- and labor-intensive observational measure that requires a couple to interact while a blinded, independent rater observes and rates their interactions using an intricate coding process. This survey structure precludes the ability to quickly and comprehensively assess a veteran’s intimate partner functioning in settings such as mental health outpatient clinics where mental health providers engage in brief, time-limited psychotherapy. As such, brief measures of intimate partner relationship functioning are needed to best inform clinical care among veterans with PTSD.

The primary aim of the current study was to create a psychometrically valid, yet brief, self-report version of the TCFES to assess multiple domains of intimate partner relationship functioning. The psychometric properties of this measure were assessed among a sample of US veterans with PTSD who were in an intimate partner relationship. We specifically examined factor structure, reliability, and associations to established measures of specific domains of relational functioning.

Methods

Ninety-four veterans were recruited via posted advertisements, promotion in PTSD therapy groups/staff meetings, and word of mouth at the Dallas Veterans Affairs Medical Center (VAMC). Participants were eligible if they had a documented diagnosis of PTSD as confirmed in the veteran’s electronic medical record and an affirmative response to currently being involved in an intimate partner relationship (ie, legally married, common-law spouse, involved in a relationship/partnership). There were no exclusion criteria.

Interested veterans were invited to complete several study-related self-report measures concerning their intimate partner relationships that would take about an hour. They were informed that the surveys were voluntary and confidential, and that they would be compensated for their participation. All veterans who participated provided written consent and the study was approved by the Dallas VAMC institutional review board.

Of the 94 veterans recruited, 3 veterans’ data were removed from current analyses after informed consent but before completing the surveys when they indicated they were not currently in a relationship or were divorced. After consent, the 91 participants were administered several study-related self-report measures. The measures took between 30 and 55 minutes to complete. Participants were then compensated $25 for their participation.

Intimate Partner Relationship Functioning

The 16-item TCFES self-report version (TCFES-SR) was developed to assess multiple domains of interpersonal functioning (Appendix). The observational TCFES assesses 5 intimate partner relationship characteristic domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict) during a couple’s interaction by an independent trained rater.¹² Each of the 16 TCFES-SR items were modeled after original constructs measured by the TCFES, including power, closeness, clarify, other’s views, responsibility, closure, negotiation, expressiveness, responsiveness, positive regard, negative regard, mood/tone, empathy, frequency, affective quality, and generalization and escalation. To maintain consistency with the TCFES, each item of the TCFES-SR was scored from 1 (severely dysfunctional) to 5 (highly functional). Additionally, all item wording for the TCFES-SR was based on wording in the TCFES manual after consultation with an expert who facilitated the development of the TCFES.¹² On average, the TCFES-SR took 5 to 10 minutes to complete.

To measure concurrent validity of the modified TCFES-SR, several additional interpersonal measures were selected and administered based on prior research and established domains of the TCFES. The Positive and Negative Quality in Marriage Scale (PANQIMS) was administered to assess perceived attitudes toward a relationship.^13,14 The PANQIMS generates 2 subscales: positive quality and negative quality in the relationship. Because the PANQIMS specifically assesses married relationships and our sample included married and nonmarried participants, wording was modified (eg, “spouse/partner”).

The relative power subscale of the Network Relationships Inventory–Relationship Qualities Version (NRI-RQV) measure was administered to assess the unequal/shared role romantic partners have in power equality (ie, relative power).¹⁵

The Revised Dyadic Adjustment Scale (RDAS) is a self-report measure that assesses multiple dimensions of marital adjustment and functioning.¹⁶ Six subscales of the RDAS were chosen based on items of the TCFES-SR: decision making, values, affection, conflict, activities, and discussion.

The Interpersonal Reactivity Index (IRI) empathetic concern subscale was administered to assess empathy across multiple contexts and situations¹⁷ and the Experiences in Close Relationships-Revised Questionnaire (ECR-R) was administered to assess relational functioning by determining attachment-related anxiety and avoidance.¹⁸

Sociodemographic Information

A sociodemographic questionnaire also was administered. The questionnaire assessed gender, age, education, service branch, length of interpersonal relationship, race, and ethnicity of the veteran as well as gender of the veteran’s partner.

Statistical Analysis

Factor structure of the TCFES-SR was determined by conducting an exploratory factor analysis. To allow for correlation between items, the Promax oblique rotation method was chosen.¹⁹ Number of factors was determined by agreement between number of eigenvalues ≥ 1, visual inspection of the scree plot, and a parallel analysis. Factor loadings of ≥ 0.3 were used to determine which items loaded on to which factors.

Convergent validity was assessed by conducting Pearson’s bivariate correlations between identified TCFES-SR factor(s) and other administered measures of interpersonal functioning (ie, PANQIMS positive and negative quality; NRI-RQV relative power subscale; RDAS decision making, values, affection, conflict, activities, and discussion subscales; IRI-empathetic concern subscale; and ECR-R attachment-related anxiety and avoidance subscales). Strength of relationship was determined based on the following guidelines: ± 0.3 to 0.49 = small, ± 0.5 to 0.69 = moderate, and ± 0.7 to 1.00 = large. Internal consistency was also determined for TCFES-SR factor(s) using Cronbach’s α. A standard level of significance (α=.05) was used for all statistical analyses.

Results

Eighty-six veterans provided complete data (Table 1). The Kaiser-Meyer-Olkin measure of sampling adequacy was indicative that sample size was adequate (.91), while Bartlett’s test of sphericity found the variables were suitable for structure detection, χ² (120) = 800.00, P < .001. While 2 eigenvalues were ≥ 1, visual inspection of the scree plot and subsequent parallel analysis identified a unidimensional structure (ie, 1 factor) for the TCFES-SR. All items were found to load to this single factor, with all loadings being ≥ 0.5 (Table 2). Additionally, internal consistency was excellent for the scale (α = .93).

Pearson’s bivariate correlations were significant (P < .05) between TCFES-SR total score, and almost all administered interpersonal functioning measures (Table 3). Interestingly, no significant associations were found between any of the administered measures, including the TCFES-SR total score, and the IRI-empathetic concern subscale (P > .05).

Discussion

These findings provide initial support for the psychometric properties of the TCFES-SR, including excellent internal consistency and the adequate association of its total score to established measures of interpersonal functioning. Contrary to the TCFES, the TCFES-SR was shown to best fit a unidimensional factor rather than a multidimensional measure of relationship functioning. However, the TCFES-SR was also shown to have strong convergent validity with multiple domains of relationship functioning, indicating that the measure of overall intimate partner relationship functioning encompasses a number of relational domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict). Critically, the TCFES-SR is brief and was administered easily in our sample, providing utility as clinical tool to be used in time-sensitive outpatient settings.

A unidimensional factor has particular strength in providing a global portrait of perceived intimate partner relationship functioning, and mental health providers can administer the TCFES-SR to assess for overall perceptions of intimate partner relationship functioning rather than administering a number of measures focusing on specific interpersonal domains (eg, decision making processes or positive/negative attitudes towards one’s relationship). This allows for the quick assessment (ie, 5-10 minutes) of overall intimate partner relationship functioning rather than administration of multiple self-report measures which can be time-intensive and expensive. However, the TCFES-SR also is limited by a lack of nuanced understanding of perceptions of functioning specific to particular domains. For example, the TCFES-SR score cannot describe intimate partner functioning in the domain of problem solving. Therefore, brief screening tools need to be developed that assess multiple intimate partner relationship domains.

Importantly, overall intimate partner relationship functioning as measured by the TCFES-SR may not incorporate perceptions of relationship empathy, as the total score did not correlate with a measure of empathetic concern (ie, the IRI-empathetic concern subscale). As empathy was based on one item in the TCFES-SR vs 7 in the IRI-empathetic concern subscale, it is unclear if the TCFES-SR only captures a portion of the construct of empathy (ie, sensitivity to partner) vs the comprehensive assessment of trait empathy that the IRI subscale measures. Additionally, the IRI-empathetic concern subscale did not significantly correlate with any of the other administered measures of relationship functioning. Given the role of empathy in positive, healthy intimate partner relationships, future research should explore the role of empathetic concern among veterans with PTSD as it relates to overall (eg, TCFES-SR) and specific aspects of intimate partner relationship functioning.²⁰

While the clinical applicability of the TCFES-SR requires further examination, this measure has a number of potential uses. Information captured quickly by the TCFES-SR may help to inform appropriate referral for treatment. For instance, veterans reporting low total scores on the TCFES-SR may indicate a need for a referral for intervention focused on improving overall relationship functioning (eg, Integrative Behavioral Couple Therapy).^21,22 Measurement-based care (ie, tracking and discussing changes in symptoms during treatment using validated self-report measures) is now required by the Joint Commission as a standard of care,and has been shown to improve outcomes in couples therapy.^23,24 As a brief self-report measure, the TCFES-SR may be able to facilitate measurement-based care and assist providers in tracking changes in overall relationship functioning over the course of treatment. However, the purpose of the current study was to validate the TCFES-SR and not to examine the utility of the TCFES-SR in clinical care; additional research is needed to determine standardized cutoff scores to indicate a need for clinical intervention.

Limitations

Several limitations should be noted. The current study only assessed perceived intimate partner relationship functioning from the perspective of the veteran, thus limiting implications as it pertains to the spouse/partner of the veteran. PTSD diagnosis was based on chart review rather than a psychodiagnostic measure (eg, Clinician Administered PTSD Scale); therefore, whether this diagnosis was current or in remission was unclear. Although our sample was adequate to conduct an exploratory factor analysis,the overall sample size was modest, and results should be considered preliminary with need for further replication.²⁵ The sample was also primarily male, white or black, and non-Hispanic; therefore, results may not generalize to a more sociodemographically diverse population. Finally, given the focus of the study to develop a self-report measure, we did not compare the TCFES-SR to the original TCFES. Thus, further research examining the relationship between the TCFES-SR and TCFES may be needed to better understand overlap and potential incongruence in these measures, and to ascertain any differences in their factor structures.

Conclusion

This study is novel in that it adapted a comprehensive observational measure of relationship functioning to a self-report measure piloted among a sample of veterans with PTSD in an intimate partner relationship, a clinical population that remains largely understudied. Although findings are preliminary, the TCFES-SR was found to be a reliable and valid measure of overall intimate partner relationship functioning. Given the rapid administration of this self-report measure, the TCFES-SR may hold clinical utility as a screen of intimate partner relationship deficits in need of clinical intervention. Replication in a larger, more diverse sample is needed to further examine the generalizability and confirm psychometric properties of the TCFES-SR. Additionally, further understanding of the clinical utility of the TCFES-SR in treatment settings remains critical to promote the development and maintenance of healthy intimate partner relationships among veterans with PTSD. Finally, development of effective self-report measures of intimate partner relationship functioning, such as the TCFES-SR, may help to facilitate needed research to understand the effect of PTSD on establishing and maintaining healthy intimate partner relationships among veterans.

Acknowledgments

The current study was funded by the Timberlawn Psychiatric Research Foundation. This material is the result of work supported in part by the US Department of Veterans Affairs; the Rocky Mountain Mental Illness Research, Education and Clinical Center (MIRECC) for Suicide Prevention; Sierra Pacific MIRECC; and the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.

Although about 8.3% of the general adult civilian population will be diagnosed with posttraumatic stress disorder (PTSD) in their lifetime, rates of PTSD are even higher in the veteran population.^1,2 PTSD is associated with a number of psychosocial consequences in veterans, including decreased intimate partner relationship functioning.^3,4 For example, Cloitre and colleagues reported that PTSD is associated with difficulty with socializing, intimacy, responsibility, and control, all of which increase difficulties in intimate partner relationships.⁵ Similarly, researchers also have noted that traumatic experiences can affect an individual’s attachment style, resulting in progressive avoidance of interpersonal relationships, which can lead to marked difficulties in maintaining and beginning intimate partner relationships.^6,7 Despite these known consequences of PTSD, as Dekel and Monson noted in a review,further research is still needed regarding the mechanisms by which trauma and PTSD result in decreased intimate partner relationship functioning among veterans.⁸ Nonetheless, as positive interpersonal relationships are associated with decreased PTSD symptom severity^9,10 and increased engagement in PTSD treatment,¹¹ determining methods of measuring intimate partner relationship functioning in veterans with PTSD is important to inform future research and aid the provision of care.

To date, limited research has examined the valid measurement of intimate partner relationship functioning among veterans with PTSD. Many existing measures that comprehensively assess intimate partner relationship functioning are time and resource intensive. One such measure, the Timberlawn Couple and Family Evaluation Scales (TCFES), comprehensively assesses multiple pertinent domains of intimate partner relationship functioning (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict).¹² By assessing multiple domains, the TCFES offers a method of understanding the specific components of an individual’s intimate partner relationship in need of increased clinical attention.¹² However, the TCFES is a time- and labor-intensive observational measure that requires a couple to interact while a blinded, independent rater observes and rates their interactions using an intricate coding process. This survey structure precludes the ability to quickly and comprehensively assess a veteran’s intimate partner functioning in settings such as mental health outpatient clinics where mental health providers engage in brief, time-limited psychotherapy. As such, brief measures of intimate partner relationship functioning are needed to best inform clinical care among veterans with PTSD.

The primary aim of the current study was to create a psychometrically valid, yet brief, self-report version of the TCFES to assess multiple domains of intimate partner relationship functioning. The psychometric properties of this measure were assessed among a sample of US veterans with PTSD who were in an intimate partner relationship. We specifically examined factor structure, reliability, and associations to established measures of specific domains of relational functioning.

Methods

Ninety-four veterans were recruited via posted advertisements, promotion in PTSD therapy groups/staff meetings, and word of mouth at the Dallas Veterans Affairs Medical Center (VAMC). Participants were eligible if they had a documented diagnosis of PTSD as confirmed in the veteran’s electronic medical record and an affirmative response to currently being involved in an intimate partner relationship (ie, legally married, common-law spouse, involved in a relationship/partnership). There were no exclusion criteria.

Interested veterans were invited to complete several study-related self-report measures concerning their intimate partner relationships that would take about an hour. They were informed that the surveys were voluntary and confidential, and that they would be compensated for their participation. All veterans who participated provided written consent and the study was approved by the Dallas VAMC institutional review board.

Of the 94 veterans recruited, 3 veterans’ data were removed from current analyses after informed consent but before completing the surveys when they indicated they were not currently in a relationship or were divorced. After consent, the 91 participants were administered several study-related self-report measures. The measures took between 30 and 55 minutes to complete. Participants were then compensated $25 for their participation.

Intimate Partner Relationship Functioning

The 16-item TCFES self-report version (TCFES-SR) was developed to assess multiple domains of interpersonal functioning (Appendix). The observational TCFES assesses 5 intimate partner relationship characteristic domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict) during a couple’s interaction by an independent trained rater.¹² Each of the 16 TCFES-SR items were modeled after original constructs measured by the TCFES, including power, closeness, clarify, other’s views, responsibility, closure, negotiation, expressiveness, responsiveness, positive regard, negative regard, mood/tone, empathy, frequency, affective quality, and generalization and escalation. To maintain consistency with the TCFES, each item of the TCFES-SR was scored from 1 (severely dysfunctional) to 5 (highly functional). Additionally, all item wording for the TCFES-SR was based on wording in the TCFES manual after consultation with an expert who facilitated the development of the TCFES.¹² On average, the TCFES-SR took 5 to 10 minutes to complete.

To measure concurrent validity of the modified TCFES-SR, several additional interpersonal measures were selected and administered based on prior research and established domains of the TCFES. The Positive and Negative Quality in Marriage Scale (PANQIMS) was administered to assess perceived attitudes toward a relationship.^13,14 The PANQIMS generates 2 subscales: positive quality and negative quality in the relationship. Because the PANQIMS specifically assesses married relationships and our sample included married and nonmarried participants, wording was modified (eg, “spouse/partner”).

The relative power subscale of the Network Relationships Inventory–Relationship Qualities Version (NRI-RQV) measure was administered to assess the unequal/shared role romantic partners have in power equality (ie, relative power).¹⁵

The Revised Dyadic Adjustment Scale (RDAS) is a self-report measure that assesses multiple dimensions of marital adjustment and functioning.¹⁶ Six subscales of the RDAS were chosen based on items of the TCFES-SR: decision making, values, affection, conflict, activities, and discussion.

The Interpersonal Reactivity Index (IRI) empathetic concern subscale was administered to assess empathy across multiple contexts and situations¹⁷ and the Experiences in Close Relationships-Revised Questionnaire (ECR-R) was administered to assess relational functioning by determining attachment-related anxiety and avoidance.¹⁸

Sociodemographic Information

A sociodemographic questionnaire also was administered. The questionnaire assessed gender, age, education, service branch, length of interpersonal relationship, race, and ethnicity of the veteran as well as gender of the veteran’s partner.

Statistical Analysis

Factor structure of the TCFES-SR was determined by conducting an exploratory factor analysis. To allow for correlation between items, the Promax oblique rotation method was chosen.¹⁹ Number of factors was determined by agreement between number of eigenvalues ≥ 1, visual inspection of the scree plot, and a parallel analysis. Factor loadings of ≥ 0.3 were used to determine which items loaded on to which factors.

Convergent validity was assessed by conducting Pearson’s bivariate correlations between identified TCFES-SR factor(s) and other administered measures of interpersonal functioning (ie, PANQIMS positive and negative quality; NRI-RQV relative power subscale; RDAS decision making, values, affection, conflict, activities, and discussion subscales; IRI-empathetic concern subscale; and ECR-R attachment-related anxiety and avoidance subscales). Strength of relationship was determined based on the following guidelines: ± 0.3 to 0.49 = small, ± 0.5 to 0.69 = moderate, and ± 0.7 to 1.00 = large. Internal consistency was also determined for TCFES-SR factor(s) using Cronbach’s α. A standard level of significance (α=.05) was used for all statistical analyses.

Results

Eighty-six veterans provided complete data (Table 1). The Kaiser-Meyer-Olkin measure of sampling adequacy was indicative that sample size was adequate (.91), while Bartlett’s test of sphericity found the variables were suitable for structure detection, χ² (120) = 800.00, P < .001. While 2 eigenvalues were ≥ 1, visual inspection of the scree plot and subsequent parallel analysis identified a unidimensional structure (ie, 1 factor) for the TCFES-SR. All items were found to load to this single factor, with all loadings being ≥ 0.5 (Table 2). Additionally, internal consistency was excellent for the scale (α = .93).

Pearson’s bivariate correlations were significant (P < .05) between TCFES-SR total score, and almost all administered interpersonal functioning measures (Table 3). Interestingly, no significant associations were found between any of the administered measures, including the TCFES-SR total score, and the IRI-empathetic concern subscale (P > .05).

Discussion

These findings provide initial support for the psychometric properties of the TCFES-SR, including excellent internal consistency and the adequate association of its total score to established measures of interpersonal functioning. Contrary to the TCFES, the TCFES-SR was shown to best fit a unidimensional factor rather than a multidimensional measure of relationship functioning. However, the TCFES-SR was also shown to have strong convergent validity with multiple domains of relationship functioning, indicating that the measure of overall intimate partner relationship functioning encompasses a number of relational domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict). Critically, the TCFES-SR is brief and was administered easily in our sample, providing utility as clinical tool to be used in time-sensitive outpatient settings.

A unidimensional factor has particular strength in providing a global portrait of perceived intimate partner relationship functioning, and mental health providers can administer the TCFES-SR to assess for overall perceptions of intimate partner relationship functioning rather than administering a number of measures focusing on specific interpersonal domains (eg, decision making processes or positive/negative attitudes towards one’s relationship). This allows for the quick assessment (ie, 5-10 minutes) of overall intimate partner relationship functioning rather than administration of multiple self-report measures which can be time-intensive and expensive. However, the TCFES-SR also is limited by a lack of nuanced understanding of perceptions of functioning specific to particular domains. For example, the TCFES-SR score cannot describe intimate partner functioning in the domain of problem solving. Therefore, brief screening tools need to be developed that assess multiple intimate partner relationship domains.

Importantly, overall intimate partner relationship functioning as measured by the TCFES-SR may not incorporate perceptions of relationship empathy, as the total score did not correlate with a measure of empathetic concern (ie, the IRI-empathetic concern subscale). As empathy was based on one item in the TCFES-SR vs 7 in the IRI-empathetic concern subscale, it is unclear if the TCFES-SR only captures a portion of the construct of empathy (ie, sensitivity to partner) vs the comprehensive assessment of trait empathy that the IRI subscale measures. Additionally, the IRI-empathetic concern subscale did not significantly correlate with any of the other administered measures of relationship functioning. Given the role of empathy in positive, healthy intimate partner relationships, future research should explore the role of empathetic concern among veterans with PTSD as it relates to overall (eg, TCFES-SR) and specific aspects of intimate partner relationship functioning.²⁰

While the clinical applicability of the TCFES-SR requires further examination, this measure has a number of potential uses. Information captured quickly by the TCFES-SR may help to inform appropriate referral for treatment. For instance, veterans reporting low total scores on the TCFES-SR may indicate a need for a referral for intervention focused on improving overall relationship functioning (eg, Integrative Behavioral Couple Therapy).^21,22 Measurement-based care (ie, tracking and discussing changes in symptoms during treatment using validated self-report measures) is now required by the Joint Commission as a standard of care,and has been shown to improve outcomes in couples therapy.^23,24 As a brief self-report measure, the TCFES-SR may be able to facilitate measurement-based care and assist providers in tracking changes in overall relationship functioning over the course of treatment. However, the purpose of the current study was to validate the TCFES-SR and not to examine the utility of the TCFES-SR in clinical care; additional research is needed to determine standardized cutoff scores to indicate a need for clinical intervention.

Limitations

Several limitations should be noted. The current study only assessed perceived intimate partner relationship functioning from the perspective of the veteran, thus limiting implications as it pertains to the spouse/partner of the veteran. PTSD diagnosis was based on chart review rather than a psychodiagnostic measure (eg, Clinician Administered PTSD Scale); therefore, whether this diagnosis was current or in remission was unclear. Although our sample was adequate to conduct an exploratory factor analysis,the overall sample size was modest, and results should be considered preliminary with need for further replication.²⁵ The sample was also primarily male, white or black, and non-Hispanic; therefore, results may not generalize to a more sociodemographically diverse population. Finally, given the focus of the study to develop a self-report measure, we did not compare the TCFES-SR to the original TCFES. Thus, further research examining the relationship between the TCFES-SR and TCFES may be needed to better understand overlap and potential incongruence in these measures, and to ascertain any differences in their factor structures.

Conclusion

This study is novel in that it adapted a comprehensive observational measure of relationship functioning to a self-report measure piloted among a sample of veterans with PTSD in an intimate partner relationship, a clinical population that remains largely understudied. Although findings are preliminary, the TCFES-SR was found to be a reliable and valid measure of overall intimate partner relationship functioning. Given the rapid administration of this self-report measure, the TCFES-SR may hold clinical utility as a screen of intimate partner relationship deficits in need of clinical intervention. Replication in a larger, more diverse sample is needed to further examine the generalizability and confirm psychometric properties of the TCFES-SR. Additionally, further understanding of the clinical utility of the TCFES-SR in treatment settings remains critical to promote the development and maintenance of healthy intimate partner relationships among veterans with PTSD. Finally, development of effective self-report measures of intimate partner relationship functioning, such as the TCFES-SR, may help to facilitate needed research to understand the effect of PTSD on establishing and maintaining healthy intimate partner relationships among veterans.

Acknowledgments

The current study was funded by the Timberlawn Psychiatric Research Foundation. This material is the result of work supported in part by the US Department of Veterans Affairs; the Rocky Mountain Mental Illness Research, Education and Clinical Center (MIRECC) for Suicide Prevention; Sierra Pacific MIRECC; and the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.

Although about 8.3% of the general adult civilian population will be diagnosed with posttraumatic stress disorder (PTSD) in their lifetime, rates of PTSD are even higher in the veteran population.^1,2 PTSD is associated with a number of psychosocial consequences in veterans, including decreased intimate partner relationship functioning.^3,4 For example, Cloitre and colleagues reported that PTSD is associated with difficulty with socializing, intimacy, responsibility, and control, all of which increase difficulties in intimate partner relationships.⁵ Similarly, researchers also have noted that traumatic experiences can affect an individual’s attachment style, resulting in progressive avoidance of interpersonal relationships, which can lead to marked difficulties in maintaining and beginning intimate partner relationships.^6,7 Despite these known consequences of PTSD, as Dekel and Monson noted in a review,further research is still needed regarding the mechanisms by which trauma and PTSD result in decreased intimate partner relationship functioning among veterans.⁸ Nonetheless, as positive interpersonal relationships are associated with decreased PTSD symptom severity^9,10 and increased engagement in PTSD treatment,¹¹ determining methods of measuring intimate partner relationship functioning in veterans with PTSD is important to inform future research and aid the provision of care.

To date, limited research has examined the valid measurement of intimate partner relationship functioning among veterans with PTSD. Many existing measures that comprehensively assess intimate partner relationship functioning are time and resource intensive. One such measure, the Timberlawn Couple and Family Evaluation Scales (TCFES), comprehensively assesses multiple pertinent domains of intimate partner relationship functioning (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict).¹² By assessing multiple domains, the TCFES offers a method of understanding the specific components of an individual’s intimate partner relationship in need of increased clinical attention.¹² However, the TCFES is a time- and labor-intensive observational measure that requires a couple to interact while a blinded, independent rater observes and rates their interactions using an intricate coding process. This survey structure precludes the ability to quickly and comprehensively assess a veteran’s intimate partner functioning in settings such as mental health outpatient clinics where mental health providers engage in brief, time-limited psychotherapy. As such, brief measures of intimate partner relationship functioning are needed to best inform clinical care among veterans with PTSD.

The primary aim of the current study was to create a psychometrically valid, yet brief, self-report version of the TCFES to assess multiple domains of intimate partner relationship functioning. The psychometric properties of this measure were assessed among a sample of US veterans with PTSD who were in an intimate partner relationship. We specifically examined factor structure, reliability, and associations to established measures of specific domains of relational functioning.

Methods

Ninety-four veterans were recruited via posted advertisements, promotion in PTSD therapy groups/staff meetings, and word of mouth at the Dallas Veterans Affairs Medical Center (VAMC). Participants were eligible if they had a documented diagnosis of PTSD as confirmed in the veteran’s electronic medical record and an affirmative response to currently being involved in an intimate partner relationship (ie, legally married, common-law spouse, involved in a relationship/partnership). There were no exclusion criteria.

Interested veterans were invited to complete several study-related self-report measures concerning their intimate partner relationships that would take about an hour. They were informed that the surveys were voluntary and confidential, and that they would be compensated for their participation. All veterans who participated provided written consent and the study was approved by the Dallas VAMC institutional review board.

Of the 94 veterans recruited, 3 veterans’ data were removed from current analyses after informed consent but before completing the surveys when they indicated they were not currently in a relationship or were divorced. After consent, the 91 participants were administered several study-related self-report measures. The measures took between 30 and 55 minutes to complete. Participants were then compensated $25 for their participation.

Intimate Partner Relationship Functioning

The 16-item TCFES self-report version (TCFES-SR) was developed to assess multiple domains of interpersonal functioning (Appendix). The observational TCFES assesses 5 intimate partner relationship characteristic domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict) during a couple’s interaction by an independent trained rater.¹² Each of the 16 TCFES-SR items were modeled after original constructs measured by the TCFES, including power, closeness, clarify, other’s views, responsibility, closure, negotiation, expressiveness, responsiveness, positive regard, negative regard, mood/tone, empathy, frequency, affective quality, and generalization and escalation. To maintain consistency with the TCFES, each item of the TCFES-SR was scored from 1 (severely dysfunctional) to 5 (highly functional). Additionally, all item wording for the TCFES-SR was based on wording in the TCFES manual after consultation with an expert who facilitated the development of the TCFES.¹² On average, the TCFES-SR took 5 to 10 minutes to complete.

To measure concurrent validity of the modified TCFES-SR, several additional interpersonal measures were selected and administered based on prior research and established domains of the TCFES. The Positive and Negative Quality in Marriage Scale (PANQIMS) was administered to assess perceived attitudes toward a relationship.^13,14 The PANQIMS generates 2 subscales: positive quality and negative quality in the relationship. Because the PANQIMS specifically assesses married relationships and our sample included married and nonmarried participants, wording was modified (eg, “spouse/partner”).

The relative power subscale of the Network Relationships Inventory–Relationship Qualities Version (NRI-RQV) measure was administered to assess the unequal/shared role romantic partners have in power equality (ie, relative power).¹⁵

The Revised Dyadic Adjustment Scale (RDAS) is a self-report measure that assesses multiple dimensions of marital adjustment and functioning.¹⁶ Six subscales of the RDAS were chosen based on items of the TCFES-SR: decision making, values, affection, conflict, activities, and discussion.

The Interpersonal Reactivity Index (IRI) empathetic concern subscale was administered to assess empathy across multiple contexts and situations¹⁷ and the Experiences in Close Relationships-Revised Questionnaire (ECR-R) was administered to assess relational functioning by determining attachment-related anxiety and avoidance.¹⁸

Sociodemographic Information

A sociodemographic questionnaire also was administered. The questionnaire assessed gender, age, education, service branch, length of interpersonal relationship, race, and ethnicity of the veteran as well as gender of the veteran’s partner.

Statistical Analysis

Factor structure of the TCFES-SR was determined by conducting an exploratory factor analysis. To allow for correlation between items, the Promax oblique rotation method was chosen.¹⁹ Number of factors was determined by agreement between number of eigenvalues ≥ 1, visual inspection of the scree plot, and a parallel analysis. Factor loadings of ≥ 0.3 were used to determine which items loaded on to which factors.

Convergent validity was assessed by conducting Pearson’s bivariate correlations between identified TCFES-SR factor(s) and other administered measures of interpersonal functioning (ie, PANQIMS positive and negative quality; NRI-RQV relative power subscale; RDAS decision making, values, affection, conflict, activities, and discussion subscales; IRI-empathetic concern subscale; and ECR-R attachment-related anxiety and avoidance subscales). Strength of relationship was determined based on the following guidelines: ± 0.3 to 0.49 = small, ± 0.5 to 0.69 = moderate, and ± 0.7 to 1.00 = large. Internal consistency was also determined for TCFES-SR factor(s) using Cronbach’s α. A standard level of significance (α=.05) was used for all statistical analyses.

Results

Eighty-six veterans provided complete data (Table 1). The Kaiser-Meyer-Olkin measure of sampling adequacy was indicative that sample size was adequate (.91), while Bartlett’s test of sphericity found the variables were suitable for structure detection, χ² (120) = 800.00, P < .001. While 2 eigenvalues were ≥ 1, visual inspection of the scree plot and subsequent parallel analysis identified a unidimensional structure (ie, 1 factor) for the TCFES-SR. All items were found to load to this single factor, with all loadings being ≥ 0.5 (Table 2). Additionally, internal consistency was excellent for the scale (α = .93).

Pearson’s bivariate correlations were significant (P < .05) between TCFES-SR total score, and almost all administered interpersonal functioning measures (Table 3). Interestingly, no significant associations were found between any of the administered measures, including the TCFES-SR total score, and the IRI-empathetic concern subscale (P > .05).

Discussion

These findings provide initial support for the psychometric properties of the TCFES-SR, including excellent internal consistency and the adequate association of its total score to established measures of interpersonal functioning. Contrary to the TCFES, the TCFES-SR was shown to best fit a unidimensional factor rather than a multidimensional measure of relationship functioning. However, the TCFES-SR was also shown to have strong convergent validity with multiple domains of relationship functioning, indicating that the measure of overall intimate partner relationship functioning encompasses a number of relational domains (ie, structure, autonomy, problem solving, affect regulation, and disagreement/conflict). Critically, the TCFES-SR is brief and was administered easily in our sample, providing utility as clinical tool to be used in time-sensitive outpatient settings.

A unidimensional factor has particular strength in providing a global portrait of perceived intimate partner relationship functioning, and mental health providers can administer the TCFES-SR to assess for overall perceptions of intimate partner relationship functioning rather than administering a number of measures focusing on specific interpersonal domains (eg, decision making processes or positive/negative attitudes towards one’s relationship). This allows for the quick assessment (ie, 5-10 minutes) of overall intimate partner relationship functioning rather than administration of multiple self-report measures which can be time-intensive and expensive. However, the TCFES-SR also is limited by a lack of nuanced understanding of perceptions of functioning specific to particular domains. For example, the TCFES-SR score cannot describe intimate partner functioning in the domain of problem solving. Therefore, brief screening tools need to be developed that assess multiple intimate partner relationship domains.

Importantly, overall intimate partner relationship functioning as measured by the TCFES-SR may not incorporate perceptions of relationship empathy, as the total score did not correlate with a measure of empathetic concern (ie, the IRI-empathetic concern subscale). As empathy was based on one item in the TCFES-SR vs 7 in the IRI-empathetic concern subscale, it is unclear if the TCFES-SR only captures a portion of the construct of empathy (ie, sensitivity to partner) vs the comprehensive assessment of trait empathy that the IRI subscale measures. Additionally, the IRI-empathetic concern subscale did not significantly correlate with any of the other administered measures of relationship functioning. Given the role of empathy in positive, healthy intimate partner relationships, future research should explore the role of empathetic concern among veterans with PTSD as it relates to overall (eg, TCFES-SR) and specific aspects of intimate partner relationship functioning.²⁰

While the clinical applicability of the TCFES-SR requires further examination, this measure has a number of potential uses. Information captured quickly by the TCFES-SR may help to inform appropriate referral for treatment. For instance, veterans reporting low total scores on the TCFES-SR may indicate a need for a referral for intervention focused on improving overall relationship functioning (eg, Integrative Behavioral Couple Therapy).^21,22 Measurement-based care (ie, tracking and discussing changes in symptoms during treatment using validated self-report measures) is now required by the Joint Commission as a standard of care,and has been shown to improve outcomes in couples therapy.^23,24 As a brief self-report measure, the TCFES-SR may be able to facilitate measurement-based care and assist providers in tracking changes in overall relationship functioning over the course of treatment. However, the purpose of the current study was to validate the TCFES-SR and not to examine the utility of the TCFES-SR in clinical care; additional research is needed to determine standardized cutoff scores to indicate a need for clinical intervention.

Limitations

Several limitations should be noted. The current study only assessed perceived intimate partner relationship functioning from the perspective of the veteran, thus limiting implications as it pertains to the spouse/partner of the veteran. PTSD diagnosis was based on chart review rather than a psychodiagnostic measure (eg, Clinician Administered PTSD Scale); therefore, whether this diagnosis was current or in remission was unclear. Although our sample was adequate to conduct an exploratory factor analysis,the overall sample size was modest, and results should be considered preliminary with need for further replication.²⁵ The sample was also primarily male, white or black, and non-Hispanic; therefore, results may not generalize to a more sociodemographically diverse population. Finally, given the focus of the study to develop a self-report measure, we did not compare the TCFES-SR to the original TCFES. Thus, further research examining the relationship between the TCFES-SR and TCFES may be needed to better understand overlap and potential incongruence in these measures, and to ascertain any differences in their factor structures.

Conclusion

This study is novel in that it adapted a comprehensive observational measure of relationship functioning to a self-report measure piloted among a sample of veterans with PTSD in an intimate partner relationship, a clinical population that remains largely understudied. Although findings are preliminary, the TCFES-SR was found to be a reliable and valid measure of overall intimate partner relationship functioning. Given the rapid administration of this self-report measure, the TCFES-SR may hold clinical utility as a screen of intimate partner relationship deficits in need of clinical intervention. Replication in a larger, more diverse sample is needed to further examine the generalizability and confirm psychometric properties of the TCFES-SR. Additionally, further understanding of the clinical utility of the TCFES-SR in treatment settings remains critical to promote the development and maintenance of healthy intimate partner relationships among veterans with PTSD. Finally, development of effective self-report measures of intimate partner relationship functioning, such as the TCFES-SR, may help to facilitate needed research to understand the effect of PTSD on establishing and maintaining healthy intimate partner relationships among veterans.

Acknowledgments

The current study was funded by the Timberlawn Psychiatric Research Foundation. This material is the result of work supported in part by the US Department of Veterans Affairs; the Rocky Mountain Mental Illness Research, Education and Clinical Center (MIRECC) for Suicide Prevention; Sierra Pacific MIRECC; and the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.