Current Psychiatry

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

CASE Grieving, delusional

Mr. M, age 51, is brought to the emergency department (ED) because of new-onset delusions and decreased self-care over the last 2 weeks following the sudden death of his wife. He has become expansive and grandiose, with pressured speech, increased energy, and markedly reduced sleep. Mr. M is preoccupied with the idea that he is “the first to survive a human reboot process” and says that his and his wife’s bodies and brains had been “split apart.” Mr. M has limited his food and fluid intake and lost 15 lb within the past 2 to 3 weeks.

Mr. M has no history of any affective, psychotic, or other major mental disorders or treatment. He reports that he has regularly used Cannabis over the last 10 years, and a few years ago, he started occasionally using nitrous oxide (N₂O). He says that in the week following his wife’s death, he used N₂O almost daily and in copious amounts. In an attempt to “self-anesthetize” himself after his wife’s funeral, he isolated himself in his bedroom and used escalating amounts of Cannabis and N₂O, while continually working on a book about their life together.

At first, Mr. M shows little emotion and describes his situation as “interesting and fascinating.” He mentions that he thinks he might have been “psychotic” the week after his wife’s death, but he shows no sustained insight and immediately relapses into psychotic thinking. Over several hours in the ED, he is tearful and sad about his wife’s death. Mr. M recalls a similar experience of grief after his mother died when he was a teenager, but at that time he did not abuse substances or have psychotic symptoms. He is fully alert, fully oriented, and has no significant deficits of attention or memory.

[polldaddy:9859135]

The authors’ observations

Grief was a precipitating event, but by itself grief cannot explain psychosis. Psychotic depression is a possibility, but Mr. M’s psychotic features are incongruent with his mood. Mania would be a diagnosis of exclusion. Mr. M had no prior history of major affective illness. Mr. M was abusing Cannabis, which might independently contribute to psychosis¹; however, he had been using it recreationally for 10 years without psychiatric problems. N₂O, however, can cause symptoms consistent with Mr. M’s presentation.

[polldaddy:9859140]

EVALUATION Laboratory tests

Mr. M’s physical examination is notable only for an elevated blood pressure of 196/120 mm Hg. Neurologic examination is normal. Toxicology is positive for cannabinoids and negative for amphetamines, cocaine, opiates, and phencyclidine. Chemistries are normal except for a potassium of 3.4 mEq/L (reference range, 3.7 to 5.2 mEq/L) and a blood urine nitrogen of 25 mg/dL (reference range, 6 to 20 mg/dL), which are consistent with reduced food and fluid intake. Mr. M shows no signs of anemia. Hematocrit is 42% and mean corpuscular volume is 90 fL. Syphilis screen is negative; a head CT scan is unremarkable.

The authors’ observations

N₂O, also known as “laughing gas,” is routinely used by dentists and pediatric anesthesiologists, and has other medical uses. Some studies have examined an adjunctive use of N₂O for pain control in the ED and during colonoscopies.^3,4

In the 2013 U.S. National Survey on Drug Use and Health, 16% of respondents reported lifetime illicit use of N₂O.^5,6 It is readily available in tanks used in medicine and industry and in small dispensers called “whippits” that can be legally purchased. Acute effects of N₂O include euphoric mood, numbness, feeling of warmth, dizziness, and auditory hallucinations.⁷ The anesthetic effects of N₂O are linked to endogenous release of opiates, and recent research links its anxiolytic activity to the facilitation of GABAergic inhibitory and N-methyl-d-aspartic acid (NMDA)-mediated transmission.⁸ Abuse of N₂O has been the presumptive cause of death in 29 cases.⁹

TREATMENT Supplementation

Mr. M is diagnosed with substance-induced psychotic disorder. His symptoms were precipitated by an acute increase in N₂O use, which has been shown to cause vitamin B₁₂ deficiency, which we consider was likely a primary contributor to his presentation. Other potential contributing factors are premorbid hyperthymic temperament, a possible propensity to psychotic thinking under stress, the sudden death of his wife, acute grief, the potentiating role of Cannabis, dehydration, and general malnutrition. The death of a loved one is associated with an increased risk of developing substance use disorders.²⁷

During a 15-day psychiatric hospitalization, Mr. M is given olanzapine, increased to 15 mg/d and oral vitamin B₁₂, 1,000 mcg/d for 4 days, then IM cyanocobalamin for 7 days. Mr. M’s symptoms steadily improve, with normalization of sleep and near-total resolution of delusions. On hospital Day 14, his vitamin B₁₂ levels are within normal limits (844 pg/mL). At discharge, Mr. M shows residual mild grandiosity, with limited insight into his illness and what caused it, but frank delusional ideation has clearly receded. He still shows some signs of grief. Mr. M is advised to stop using Cannabis and N₂O and about the potential consequences of continued use.

The authors’ observations

For patients with vitamin B₁₂ deficiency, guidelines from the National Health Service in the United Kingdom and the British Society for Haematology recommend treatment with IM hydroxocobalamin, 1,000 IU, 3 times weekly, for 2 weeks.^21,28 For patients with neurologic symptoms, the British National Foundation recommends treatment with IM hydroxocobalamin, 1,000 IU, on alternative days until there is no further improvement.²¹

This case is a reminder for clinicians to screen for inhalant use, specifically N₂O, which can precipitate vitamin B₁₂ deficiency with psychiatric symptoms as the only presenting concern. Clinicians should consider measuring vitamin B₁₂ levels in psychiatric patients at risk of deficiency of this nutrient, including older adults, vegetarians, and those with alimentary disorders.^29,30 Dietary sources of vitamin B₁₂ include meat, milk, egg, fish, and shellfish.³¹ The body can store a total of 2 to 5 mg of vitamin B₁₂; thus, it takes 2 to 5 years to develop vitamin B₁₂ deficiency from malabsorption and can take as long as 20 years to develop vitamin B₁₂ deficiency from vegetarianism.³² However, by chemically inactivating vitamin B₁₂, N₂O causes a rapid functional deficiency, as was seen in our patient.

OUTCOME Improved insight

At a 1-week follow-up appointment with a psychiatrist, Mr. M has no evident psychotic symptoms. He reports that he has not used Cannabis or N₂O, and he discontinues olanzapine following this visit. Two weeks later, Mr. M shows no psychotic or affective symptoms other than grief, which is appropriately expressed. His insight has improved. He commits to not using Cannabis, N₂O, or any other illicit substances. Mr. M is referred back to his long-standing primary care provider with the understanding that if any psychiatric symptoms recur he will see a psychiatrist again.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

As physicians, we are cognizant of the importance of patient-centered care, active listening, empathy, and patience—the so-called “hidden curriculum of medicine.”¹ However, our attempts to centralize these concepts may be overshadowed by the deeply rooted drive to treat and fix. At times, we are simply treating uncertainty, whether it be diagnostic uncertainty or the uncertainty arising from clinical responses and outcomes that are far from binary. Definitive actions, such as adding medications or altering dosages, may appear to both patients and physicians to be a step closer to a “cure.” However, watchful waiting, re-evaluation, and accepting uncertainty are the true skills of effective care.

Be savvy about psychopharmacology

Psychotropics can take weeks to months to reach their full potential, and have varying responses and adverse effects. Beware of changing regimens prematurely, and keep in mind basic, yet crucial, pharma­cokinetic concepts (eg, 4 to 5 half-lives to reach steady state, variations in metabolism). Receptor binding and dosing heuristics are notably common in psychiatry. Although such concepts are important to grasp, there is no one-size-fits-all rule. The brain simply does not possess the heart’s machine-like, linear functioning. Therefore, targeting individual parts (ie, receptors) will not equate to fixing the whole organ systematically or predictably.

Is the patient truly treatment-resistant?

Even the best treatment regimen has no clinical benefit if the patient cannot afford the prescription or does not take the medication. If cost is an impediment, switch from brand name drugs to generic formulations or to older medications in the same class. Before declaring the patient “treatment-resistant” and making medication changes, assess for compliance. This may require assistance from collateral informants. Ask family members to count the number of pills remaining in the bottle, and call the pharmacy to find out the last refill dates. If the patient exhibits a partial response to what should be a therapeutic dose, consider obtaining drug plasma levels to rule out rapid metabolism before deeming the medication trial a failure.²

Medications as liabilities

Overreliance on medications can result in the medications becoming liabilities. The polypharmacy problem is not unique to psychiatry.³ However, psychiatric patients may be more likely to inadvertently use medications in a maladaptive manner and disrupt the fundamental goals of long-term care. Avoid making medication adjustments in response to a patient’s life stressors and normative situational reactions. Doing so is a disservice to patients, because we are robbing them of chances to develop necessary coping skills and defenses. This can be overtly damaging in certain patient populations, such as those with borderline personality disorder, who may use medication adjustments as a crutch during crises.⁴

Treat the patient, not yourself

We physicians mean well in prescribing evidence-based treatments; however, if the symptoms or adverse effects are not bother­some or cause functional impairment, we risk losing sight of the patient’s goals in treatment and imposing our own instead. Displacing the treatment focus can alienate the patient, harm the therapeutic alliance, and result in “pill fatigue.” For example, we may be tempted to treat antipsychotic-induced tardive dyskinesia, even if the patient is not concerned about abnormal movements. Although we see this adverse effect as a secondary problem that necessitates treatment, from the patient’s perspective, taking additional medication may be a far greater burden. The patient’s perception of direct beneficial effects from medications is crucial not only for patient-oriented care but also for adherence.⁵

Change does not happen overnight

Picking a treatment option out of a lineup of choices, à la UWorld questions, does not always translate into patients agreeing with the suggested treatment, let alone the idea of receiving treatment at all. Motivational interviewing is our chance to shine in such situations and the reason why we are physicians, rather than answer-picking bots. Patients cannot change if they are not ready. However, we should be ready to roll with resistance while looking for signs of readiness to change. We must accept that it may take a week, a month, a year, or even longer for patients to align with our plan of action. The only futile decision is deeming our efforts as futile while discounting the benefits of incremental care.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Although the biological aspects of psychiatry are crucial, psychotherapy is an integral part of psychiatry. Unfortunately, the emphasis on psychotherapy training in psychiatry residency programs has declined compared with a decade or more ago. In an era of dwindling psychotherapy training and resources, the quality and type of psychotherapy training has become more variable. In addition to helping maintain the therapeutic alliance, nuanced psychotherapy by a trained professional can be transformational by helping patients to:

• process complex life events and emotions
• feel understood
• overcome psychological barriers to recovery
• enhance self-esteem.

For the therapist, effective psychotherapy usually involves warmth and empathy, active listening, an authentic and genuine positive regard for the patient and his (her) experiences. The therapist should also pay attention to her (his) own emotions and internal responses, as well as the patient’s, while having the perseverance to address and help the patient work through challenging aspects.

When providing psychotherapy for adult patients, consider these basic, but salient points that are often overlooked.

Refrain from making life decisions for patients, except in exceptional circumstances, such as in situations of abuse and other crises.¹ Telling an adult patient what to do about life decisions that he finds challenging fits more under life coaching than psychotherapy. Through therapy, patients should be helped in processing the pros and cons of certain decisions and in navigating the decision-making process to arrive at a decision that makes the most sense to them. Also, it’s not uncommon for thera­peutic relationships to rupture when therapists give advice such as suggesting that a patient divorce his spouse, date a certain individual, or have children.

There are many reasons why giving advice in psychotherapy is not recommended. Giving advice can be an impediment to the therapeutic process.² What is good advice for one patient may not be good for another. Therapists who give advice often do so from their own lens and perspective. This perspective may not only be different from the patient’s priorities and life circumstances, but the therapist also may have inadequate information about the patient’s situation,^1,2 which could lead to providing advice that could even harm the patient. In addition, providing advice might prevent a patient from gaining adequate agency or self-directedness while promoting an unhealthy dependence on the therapist and reinforcing the patient’s self-doubt or lack of confidence. In these cases, the patient may later resent the therapist for the advice.

Address the ‘here and now.’¹ Pay attention to immediate issues or themes that emerge, and address them with the patient gently and thoughtfully, as appropriate. Ignoring these may create risks of missing vital, underlying material that could reveal more of the patient’s inner world, as these themes can sometimes reflect other themes of the patient’s life outside of treatment.

Acknowledging and empathizing, when appropriate, are key initial steps that help decrease resistance and facilitate the therapeutic process.

Explore the affect. Paying attention to the patient’s emotional state is critical.³ This holds true for all types of psychotherapy. For example, if a patient suddenly becomes tearful when telling his story or describing recent events, this is usually a sign that the subject matter affects or holds value to the patient in a significant or meaningful way and should be further explored.

‘Meet the patient where they are.’ This doesn’t mean you should yield to the patient or give in to his demands. It implies that you should assess the patient’s readiness for a particular intervention and devise interventions from that standpoint, exploring the patient’s ambivalence, noticing resistance, and continuing to acknowledge and empathize with where the patient is in life or treatment. When utilized judiciously, this technique can help the therapist align with the patient, and help the patient move forward through resistance and ambivalence.

Be nonjudgmental and empathetic. Patients place trust in their therapists when they disclose thoughts or emotions that are sensitive, meaningful, or close to the heart. A nonjudgmental response helps the patient accept his experiences and emotions. Being empathetic requires putting oneself in another’s shoes; it does not mean agreeing with the patient. Of course, if you learn that your patient abused a child or an older adult, you are required to report it to the appropriate state agency. In addition, follow the duty to warn and protect in case of any other safety issues, as appropriate.

Do not assume. Open-ended questions and exploration are key. For example, a patient told her resident therapist that her father recently passed away. The therapist expressed to the patient how hard this must be for her. However, the patient said she was relieved by her father’s death, because he had been abusive to her for years. Because of the therapist’s comment, the patient doubted her own reaction and felt guilty for not being more upset about her father’s death.

Avoid over-identifying with your patient. If you find yourself over-identifying with a patient because you have a common background or life events, seek supervision. Over-identification not only can pose barriers to objectively identifying patterns and trends in the patient’s behavior or presentation but also can increase the risk of crossing boundaries or even minimizing the patient’s experience. Exercise caution if you find yourself wanting to be liked by your patient; this is a common mistake among beginning therapists.⁴

Seek supervision. If you are feeling angry, frustrated, indifferent, or overly attached toward a patient, recognize this countertransference and seek consultation or supervision from an experienced colleague or supervisor. These emotions can be valuable tools that shed light not only on the patient’s life and the session itself, but also help you identify any other factors, such as your own feelings or experiences, that might be contributing to these reactions.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Despite a lack of evidence, polypharmacy often is used to treat autism spectrum disorder (ASD),¹ while educational techniques are underutilized. Compared with the general population, children with ASD may be more prone to the adverse effects of the medications used to treat symptoms, such as antipsychotics and antidepressants.² Therefore, when addressing problem behaviors, such as tantrums, aggressiveness, or self-injury, in a patient with ASD, before prescribing a medication, consider the ABCs of these behaviors.³

Antecedents. What happened before the behavior occurred? Where and when did the behavior occur? Was the individual unable to get a desired tangible item, such as a preferred food, toy, or another object? Was the individual told complete a task that he (she) did not want to do? Did the individual see someone else getting attention?

Behaviors. What behavior(s) occurred after each antecedent?

Consequences. What happened after the behavior occurred? Did the caregiver give the individual the item he wanted? Was the individual able to get out of doing work that he did not want to do or become the center of attention?

Having parents document the ABCs is useful not only for finding out why a behavior occurred, but also for objectively determining if and how a medication is affecting the frequency of a behavior. Charts that parents can use to document ABC data are available online (eg, http://www.positively­autism.com/downloads/datasheet_abc.pdf). Once this data is collected, it can be used to implement appropriate interventions, which I describe as DEFG.

Differential reinforcement of other behaviors is a procedure that provides positive reinforcement for not engaging in a problem behavior or for staying on task. For example, use a token board to reward positive behaviors, with physical tokens or written marks. However, some patients require immediate reinforcement. I suggest that parents or caregivers carry small pieces of preferred food to give to the patient to reinforce positive behavior.

Exercise. A review of 18 studies reported that physical exercise, such as jogging, weight training, and bike riding, can help reduce problem behaviors in individuals with ASD.⁴ Among 64 participants with ASD, there was a decrease in aggression, stereotypy, off-task behavior, and elopement, and improvements in on-task and motor behavior such as playing catch.

Function. Refer to the ABCs to determine why a specific problem behavior is occurring. Each behavior can have 1 or multiple functions; therefore, develop a plan specific to the reason the patient engages in the behavior. For example, if the individual engages in a behavior to avoid a task, the parent or caregiver can give individual tokens that the individual can later exchange for a break, instead of engaging in the problem behavior to avoid the task. If a behavior appears to be done for attention, instruct the caregivers to provide frequent periods of attention when the individual engages in positive behaviors.

Go to the appropriate placement. By law, persons age ≤21 have the right to an education and to make meaningful progress. If a patient with ASD exhibits behaviors that interfere with learning, he is entitled to a placement that can provide intensive applied behavior analysis. If you feel that the child needs a different school, write an evaluation for the parent or guardian to submit to the school district and clearly outline the patient’s needs and requirements.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Most psychiatrists are required to sign an employment contract before taking a job, but few of us have received any training on reviewing such contracts. We often rely on coworkers and attorneys to navigate this process for us. However, the contract is crucial, because it outlines your employer’s clinical and administrative expectations for the position, and it gives you the opportunity to lay out what you want.¹ Because an employment contract is legally binding, you should thoroughly read it and look for clauses that may not work in your best interest. Although not a complete list, the following items should be reviewed before signing a contract.^1,2
 

Benefits. Make sure you are offered a reasonable salary, but balance the dollar amount with benefits such as:

• continuing medical education allowances
• educational loan forgiveness
• health/malpractice/disability insurance
• retirement benefits
• compensation for call schedule.

In some cases, there may be a delay before you are eligible to obtain certain benefits.

Work expectations. Many contracts state that the position is “full-time” or have other nonspecific parameters for work expectations. You should inquire about objective work parameters, such as duty hours, the average frequency of the current call schedule, timeframe for completing medical documentation, and penalties for not meeting clinical or administrative requirements, so you are not surprised by:

• working longer-than-planned shifts
• performing on-call duties
• working on days that you were not expecting
• having your credentialing status placed in jeopardy.

Some group practices allow for a half-day of no scheduled appointments with patients, so you can complete paperwork and return phone calls.

Noncompete clause. This restricts you from working within a certain geographic area or for a competing employer for a finite time period after the contract terminates or expires. A noncompete clause could restrict you from practicing within a large geographical area, especially if the job is located in a densely populated area. Some noncompete clauses do not include a temporal or geographic restriction, but can limit your ability to bring patients with you to a new practice or facility when the contract expires.

Malpractice insurance. Two types of malpractice insurance are occurrence and claims-made:

• Occurrence insurance protects you whenever an action is brought against you, even if the action is brought after the contract terminates or expires.
• Claims-made insurance provides coverage if the policy with the same insurer was in effect when the malpractice was committed and when the actual action was commenced.

Although claims-made insurance is less expensive, it can leave you without coverage should you leave your employer and no longer maintain the same insurance policy. Claims-made can be converted into occurrence through the purchase of a tail endorsement. If the employer does not offer you tail coverage, then it is your responsibility to pay for this insurance, which can be expensive.

Termination language. Every contract features a termination section that lists potential causes for terminating your employment. This list is usually not exhaustive, but it sets the framework for a realistic view of reasonable causes. Contracts also commonly contain provisions that permit termination “without cause” after notice of termination is provided. Although you could negotiate for more notice time, “without cause” clauses are unlikely to be removed from the contract.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

Throughout my 40 years in private psychiatric practice, I have found some treatments for premenstrual syndrome (PMS) that were not mentioned in “Etiology of premenstrual dysphoric disorder: 5 interwoven pieces” (Evidence-Based Reviews, Current Psychiatry. September 2017, p. 20-28).

This started in 1972 when I was serving in the Army in Oklahoma. A 28-year-old woman with severe PMS had been treated by internal medicine, an OB/GYN, and endocrinology, all to no avail. Three days before her menses began, she would start driving north. When menses commenced, she would find herself in Nebraska and have to call her husband so he could wire her money to come back.

Through my evaluation, I found that she would gain 10 lb before her menses. I prescribed a diuretic and instructed her to start taking it when she began swelling and to stop taking it after her menses began. This alleviated all of her symptoms. If a woman gains more than 3 to 5 lb, her brain also will swell, along with everything else. Because the brain is encapsulated in the skull, the swelling puts pressure on the brain, which might have been the cause of these brief psychotic episodes.

If a woman who develops PMS does not experience significant weight gain, the first thing I try is vitamin B6, 100 mg/d, prior to menses. Vitamin B6 is a cofactor in the production of numerous neurotransmitters. I found that prescribing vitamin B6 would alleviate about 20% of PMS symptoms. If the patient has a personal or family history of affective disorder, I often try antidepressants prior to menses, which alleviate approximately another 20% of her symptoms. If none of the previous 3 factors are present, I often add a low dose of progesterone, which appears to help. If all else fails, I will try a low dose of lithium, 300 mg/d, before menses. This also seems to have some positive effect.

I have not written an article about these approaches to PMS, although I have discussed them with OB/GYNs, who never seem to follow these recommendations. Because I am not university-based, I have not been able to put these treatments to scientific scrutiny. It would be helpful to conduct clinical trials to attempt to substantiate my clinical findings.

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Antipsychotics are FDA-approved as a primary treatment for schizophrenia and bipolar disorder and as adjunctive therapy for major depressive disorder. In the United States, approximately 26% of antipsychotic prescriptions written for these indications are for individuals age >65.¹ Additionally, antipsychotics are widely used to treat behavioral symptoms associated with dementia.¹ The rapid expansion of the use of second-generation antipsychotics (SGAs), in particular, has been driven in part by their lower risk for extrapyramidal symptoms (EPS) compared with first-generation antipsychotics (FGAs).¹ However, a growing body of data indicates that all antipsychotics have a range of adverse effects in older patients. This focus is critical in light of demographic trends—in the next 10 to 15 years, the population age >60 will grow 3.5 times more rapidly than the general population.²

In this context, psychiatrists need information on the relative risks of antipsychotics for older patients. This 3-part series summarizes findings and recommendations on safety and tolerability when prescribing antipsychotics in older individuals with chronic psychotic disorders, such as schizophrenia, bipolar disorder, depression, and dementia. This review aims to:

• briefly summarize the major studies and analyses relevant to older patients with these diagnoses
• provide a summative opinion on safety and tolerability issues in these older adults
• highlight the gaps in the evidence base and areas that need additional research.

Part 1 focuses on older adults with schizophrenia or bipolar disorder. Subsequent articles will focus on prescribing antipsychotics to older adults with depression and those with dementia.

Schizophrenia

Summary of benefits, place in treatment armamentarium. Individuals with schizophrenia have a shorter life expectancy than that of the general population mostly as a result of suicide and comorbid physical illnesses,³ but the number of patients with schizophrenia age >55 will double over the next 2 decades.⁴ With aging, both positive and negative symptoms may be a focus of treatment (Table 1).^5,6 Antipsychotics are a first-line treatment for older patients with schizophrenia with few medication alternatives.⁷ Safety risks associated with antipsychotics in older people span a broad spectrum (Table 2).⁸

A 6-week prospective RCT evaluated paliperidone extended-release vs placebo in 114 older adults (age ≥65 years; mean age, 70 years) with schizophrenia.¹⁴ There was an optional 24-week extension of open-label treatment with paliperidone. Mean daily dose of paliperidone was 8.4 mg. Efficacy measures did not show consistent statistically significant differences between treatment groups. Discontinuation rates were similar between paliperidone (7%) vs placebo (8%). Serious adverse events occurred in 3% of paliperidone-treated vs 8% of placebo-treated patients. Elevated prolactin levels occurred in one-half of paliperidone-treated patients. There were no prolactin or glucose treatment-related adverse events or significant mean changes in body weight for either paliperidone-treated or placebo-treated patients. Safety findings in the 24-week, open-label extension group were consistent with the RCT results.

Howanitz et al¹⁵ conducted a 12-week, prospective RCT that compared clozapine (mean dose, 300 mg/d) with chlorpromazine (mean dose, 600 mg/d) in 42 older adults (mean age, 67 years) with schizophrenia. Drop-out rate prior to 5 weeks was 19% and similar between groups. Common adverse effects included sialorrhea, hematologic abnormalities, sedation, tachycardia, EPS, and weight gain. Although both drugs were effective, more patients taking clozapine had tachycardia and weight gain, while more chlorpromazine patients reported sedation.

There have been other, less rigorous studies.^7,8 Most of these studies evaluated risperidone and olanzapine, and most were conducted in “younger” geriatric patients (age <75 years). Although patients who participate in clinical trials may be healthier than “typical” patients, adverse effects such as EPS, sedation, and weight gain were still relatively common in these studies.

Other clinical data. A major consideration in treating older adults with schizophrenia is balancing the need to administer an antipsychotic dose high enough to alleviate psychotic symptoms while minimizing dose-dependent adverse effects. There is a U-shaped relationship between age and vulnerability to antipsychotic adverse effects,^16,17 wherein adverse effects are highest at younger and older ages. Evidence supports using the lowest effective antipsychotic dose for geriatric patients with schizophrenia. Positive emission tomography (PET) studies suggest that older patients develop EPS with lower doses despite lower receptor occupancy.^17,18 A recent study of 35 older patients (mean age, 60.1 years) with schizophrenia obtained PET, clinical measures, and blood pharmacokinetic measures before and after reduction of risperidone or olanzapine doses.¹⁸ A ≥40% reduction in dose was associated with reduced adverse effects, particularly EPS and elevation of prolactin levels. Moreover, the therapeutic window of striatal D2/D3 receptor occupancy appeared to be 50% to 60% in these older patients, compared with 65% to 80% in younger patients.

Long-term risks of antipsychotic treatment across the lifespan are less clear, with evidence suggesting both lower and higher mortality risk.^19,20 It is difficult to fully disentangle the long-term risks of antipsychotics from the cumulative effects of lifestyle and comorbidity among individuals who have lived with schizophrenia for decades. Large naturalistic studies that include substantial numbers of older people with schizophrenia might be a way to elicit more information on long-term safety. The Schizophrenia Outpatient Health Outcome (SOHO) study was a large naturalistic trial that recruited >10,000 individuals with schizophrenia in 10 European countries.²¹ Although the SOHO study found differences between antipsychotics and adverse effects, such as EPS, weight gain, and sexual dysfunction, because the mean age of these patients was approximately 40 years and the follow-up period was only 3 years, it is difficult to draw conclusions that could be relevant to older individuals who have had schizophrenia for decades.

Bipolar Disorder

A secondary analysis of mixed-age, RCTs examined response in older adults (age ≥55 years) with bipolar I depression who received lurasidone as monotherapy or adjunctive therapy.³² In the monotherapy study, these patients were randomized to 6 weeks of lurasidone 20 to 60 mg/d, lurasidone 80 to 120 mg/d, or placebo. In the adjunctive therapy study, they were randomized to lurasidone 20 to 120 mg/d or placebo with either lithium or valproate. There were 83 older adults (17.1% of the sample) in the monotherapy study and 53 (15.6%) in the adjunctive therapy study. Mean improvement in depression was significantly higher for both doses of lurasidone monotherapy than placebo. Adjunctive lurasidone was not associated with statistically significant improvement vs placebo. The most frequent adverse events in older patients on lurasidone monotherapy 20 to 60 mg/d or 80 to 120 mg/d were nausea (18.5% and 9.7%, respectively) and somnolence (11.1% and 0%, respectively). Akathisia (9.7%) and insomnia (9.7%) were the most common adverse events in the group receiving 80 to 120 mg/d, with the rate of akathisia exhibiting a dose-related increase. Weight change with lurasidone was similar to placebo, and there were no clinically meaningful group changes in vital signs, electrocardiography, or laboratory parameters.

A small (N = 20) open study found improvement in older adults with bipolar depression with aripiprazole (mean dose, 10.3 mg/d).³³ Adverse effects included restlessness and weight gain (n = 3, 9% each), sedation (n = 2, 10%), and drooling and diarrhea/loose stools (n = 1, 5% each). In another small study (N = 15) using asenapine (mean dose, 11.2 mg/d) in mainly older bipolar patients with depression, the most common adverse effects were gastrointestinal (GI) discomfort (n = 5, 33%) and restlessness, tremors, cognitive difficulties, and sluggishness (n = 2, 13% each).³⁴

Clinical trials: Bipolar mania. Researchers conducted a pooled analysis of two 12-week randomized trials comparing quetiapine with placebo in a mixed-age sample with bipolar mania.³⁵ In a subgroup of 59 older patients (mean age, 62.9 years), manic symptoms improved significantly more with quetiapine (modal dose, 550 mg/d) than with placebo. Adverse effects reported by >10% of older patients were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness. Insomnia was reported by >10% of patients receiving placebo.

In a case series of 11 elderly patients with mania receiving asenapine, Baruch et al³⁶ reported a 63% remission rate. One patient discontinued the study because of a new rash, 1 discontinued after developing peripheral edema, and 3 patients reported mild sedation.

Beyer et al³⁷ reported on a post hoc analysis of 94 older adults (mean age, 57.1 years; range, 50.1 to 74.8 years) with acute bipolar mania receiving olanzapine (n = 47), divalproex (n = 31), or placebo (n = 16) in a pooled olanzapine clinical trials database. Patients receiving olanzapine or divalproex had improvement in mania; those receiving placebo did not improve. Safety findings were comparable with reports in younger patients with mania.

Other clinical data. Adverse effects found in mixed-age samples using secondary analyses of clinical trials need to be interpreted with caution because these types of studies usually exclude individuals with significant medical comorbidity. Medical burden, cognitive impairment, or concomitant medications generally necessitate slower drug titration and lower total daily dosing. For example, a secondary analysis of the U.S. National Institute of Health-funded Systematic Treatment Enhancement Program for Bipolar Disorder study, which had broader inclusion criteria than most clinical trials, reported that, although recovery rates in older adults with bipolar disorder were fairly good (78.5%), lower doses of risperidone were used in older vs younger patients.³⁸

Clinical considerations

Interpretation of the relative risks of antipsychotics in older people must be tempered by the caveat that there is limited high-quality data (Table 4). Antipsychotics are the first-line therapy for older patients with schizophrenia, although their use is supported by a small number of prospective RCTs. SGAs are preferred because of their lower propensity to cause EPS and other motor adverse effects. Older persons with schizophrenia have an EPS threshold lower than younger patients and determining the lowest effective dosage may minimize EPS and cognitive adverse effects. As individuals with long-standing schizophrenia get older, their antipsychotic dosages may need to be reduced, and clinicians need to monitor for adverse effects that are more common among older people, such as tardive dyskinesia and metabolic abnormalities. In healthy, “younger” geriatric patients, monitoring for adverse effects may be similar to monitoring of younger patients. Patients who are older or frail may need more frequent assessment.

Like older adults with schizophrenia, geriatric patients with bipolar disorder have reduced drug tolerability and experience more adverse effects than younger patients. There are no prospective controlled studies that evaluated using antipsychotics in older patients with bipolar disorder. In older bipolar patients, the most problematic adverse effects of antipsychotics are akathisia, parkinsonism, other EPS, sedation and dizziness (which may increase fall risk), and GI discomfort. A key tolerability and safety consideration when treating older adults with bipolar disorder is the role of antipsychotics in relation to the use of lithium and mood stabilizers. Some studies have suggested that lithium has neuroprotective effects when used long-term; however, at least 1 report suggested that long-term antipsychotic treatment may be associated with neurodegeneration.³⁹

The literature does not provide strong evidence on the many clinical variations that we see in routine practice settings, such as combinations of drug treatments or drugs prescribed to patients with specific comorbid conditions. There is a need for large cohort studies that monitor treatment course, medical comorbidity, and prognosis. Additionally, well-designed clinical trials such as the DART-AD, which investigated longer-term trajectories of people with dementia taking antipsychotics, should serve as a model for the type of research that is needed to better understand outcome variability among older people with chronic psychotic or bipolar disorders.⁴⁰

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.

Borderline personality disorder (BPD) is associated with impaired psychosocial functioning,^1-4 reduced health-related quality of life,⁵ high utilization of services,^6,7 and excess mortality.^8-10 Although BPD occurs in up to 40% of psychiatric inpatients¹¹ and 10% of outpatients,¹² it is underrecognized.^13-15 Often, patients with BPD do not receive an accurate diagnosis until ≥10 years after initially seeking treatment.¹⁶ The treatment and clinical implications of failing to recognize BPD include overprescribing medication and underutilizing empirically effective psychotherapies.¹⁴

This review summarizes studies of the underdiagnosis of BPD in routine clinical practice, describes which patients should be screened, and reviews alternative approaches to screening.

Underrecognition of BPD

The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is an ongoing clinical research study involving the integration of research assessment methods into routine clinical practice.¹⁷ In an early report from the MIDAS project, BPD diagnoses derived from structured and unstructured clinical interviews were compared between 2 groups of psychiatric outpatients in the same practice.¹⁵ Individuals in the structured interview cohort were 35 times more often diagnosed with BPD than individuals evaluated with an unstructured clinical interview. Importantly, when the information from the structured interview was presented to the clinicians, BPD was more likely to be diagnosed clinically.

Other studies^13,16 also found that the rate of diagnosing BPD was higher when the diagnosis was based on a semi-structured diagnostic interview compared with an unstructured clinical interview, and that clinicians were reluctant to diagnose BPD during their routine intake diagnostic evaluation.

Clinicians, however, do not use semi-structured interviews in their practice, and they also do not tend to diagnose personality disorders (PDs) based on direct questioning, as they typically would when assessing a symptom-based disorder such as depression or anxiety. Rather, clinicians report that they rely on longitudinal observations to diagnose PDs.¹⁸ However, the results from the MIDAS project were inconsistent with clinicians’ reports. When clinicians were presented with the results of the semi-structured interview, they usually would diagnose BPD, even though it was the initial evaluation. If clinicians actually relied on longitudinal observations and considered information based on the direct question approach of research interviews to be irrelevant or invalid, then the results from the semi-structured interview should not have influenced the rate at which they diagnosed BPD. This suggests that the primary issue in diagnosing PDs is not the need for longi­tudinal observation but rather the need for more information, and that there is a role for screening questionnaires.

One potential criticism of studies demonstrating underrecognition of BPD in clinical practice is that patients typically were interviewed when they presented for treatment, when most were depressed or anxious. The possible pathologizing effects of psychiatric state on personality have been known for years.¹⁹ However, a large body of literature examining the treatment, prognostic, familial, and biological correlates of PDs supports the validity of diagnosing PDs in this manner. Moreover, from a clinical perspective, the sooner a clinician is aware of the presence of BPD, the more likely this information can be used for treatment planning.

Who should be screened for BPD?

BPD is underrecognized and underdiagnosed because patients with BPD often also have comorbid mood, anxiety, or substance use disorders.^20,21 The symptoms associated with these disorders are typically the chief concern of patients with undiagnosed BPD who present for treatment. Patients with BPD rarely present for an intake evaluation and state that they are struggling with abandonment fears, chronic feelings of emptiness, or an identity disturbance. If patients identified these problems as their chief concerns, BPD would be easier to recognize.

Although several studies have documented the frequency of BPD in patients with a specific psychiatric diagnosis such as major depressive disorder (MDD) or attention-deficit/hyperactivity disorder,^22-26 the MIDAS project examined the frequency of BPD in patients with various diagnoses and evaluated which disorders were associated with a significantly increased rate of BPD.²⁷ The highest rate of BPD was found in patients with bipolar disorder. Approximately 25% of patients with bipolar II disorder and one-third of those with bipolar I disorder were diagnosed with BPD; these rates were significantly higher than the rate of BPD in patients without these disorders (Table 1²⁷). The rate of BPD was second highest in patients with a principal diagnosis of posttraumatic stress disorder (PTSD) and MDD; however, the rate of BPD in these patients was not significantly elevated compared with patients who did not have these principal diagnoses. Three disorders were associated with a significantly lower rate of BPD: adjustment disorder, dysthymic disorder, and generalized anxiety disorder.

A brief review of screening statistics

Screening tests for most psychiatric disorders are based on multi-item scales in which a total score is computed from a sum of item scores, and a cutoff point is established to determine who does and does not screen positive on the test. However, sensitivity, specificity, and positive and negative predictive values are not invariant properties of a screening test with a continuous score distribution. Rather, the performance statistics of a scale can be altered by changing the threshold score to distinguish cases from non-cases. When the screening threshold is lowered, sensitivity increases and specificity decreases.

For screening, a broad net needs to be cast so that all (or almost all) cases are included. Therefore, the cutoff score should be set low to prioritize the sensitivity of the instrument. A screening scale also should have high negative predictive value so that the clinician can be confident that patients who screen negative on the test do not have the disorder.

Screening questionnaires for BPD

Several questionnaires have been developed to screen for PDs (Table 2^28-35). Some screen for each of the DSM PDs,^28,36-42 and some screen more broadly for the presence or absence of any PD.^29,43,44 The most commonly studied self-report scale for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD),³⁰ a 10-item self-report scale derived from a subset of questions from the BPD module of a semi-structured diagnostic interview.

The initial validation study³⁰ found that the optimal cutoff score was 7, which resulted in a sensitivity of 81% and specificity of 89%. Three studies have evaluated the scale in adolescents and young adults,^45-47 and 3 studies examined the scale in adult outpatients.^48-50 Across all 6 studies, at the optimal cutoff scores determined in each study, the sensitivity of the MSI-BPD ranged from 68% to 94% (mean, 80%) and the specificity ranged from 66% to 80% (mean, 72%).

Problems with screening questionnaires. Although screening scales have been developed for many psychiatric disorders, they have not been widely used in mental health settings. In a previous commentary, I argued that the conceptual justification for using self-report screening scales for single disorders in psychiatric settings is questionable.⁵¹ Another problem with screening scales is their potential misuse as case-finding instruments. In the literature on bipolar disorder screening, several researchers misconstrued a positive screen to indicate caseness.⁵¹ Although this is not a problem with the screening measures or the selection of a cutoff score, caution must be taken to not confuse screening with diagnosis.⁵²

Screening for BPD as part of your diagnostic interview

An alternative approach to using self-administered questionnaires for screening is for clinicians to include questions in their evaluation as part of a psychiatric review of systems. When conducting a diagnostic interview, clinicians typically screen for disorders that are comorbid with the principal diagnosis by asking about the comorbid disorders’ necessary features or “gate criteria.” For example, in a patient with a principal diagnosis of MDD, the clinician would inquire about the presence of panic attacks, excessive worry, or substance use to screen for the presence of panic disorder, generalized anxiety disorder, or a substance use disorder. In contrast, for polythetically defined disorders such as BPD, there is no single gate criterion, because the disorder is diagnosed based on the presence of at least 5 of 9 criteria and no single one of these criteria is required to be present to establish the diagnosis.

As part of the MIDAS project, the psycho­metric properties of the BPD criteria were examined to determine if it was possible to identify 1 or 2 criteria that could serve as gate criteria to screen for the disorder. If the sensitivity of 1 criterion or a combination of 2 BPD criteria was sufficiently high (ie, >90%), then the assessment of this criterion (or these criteria) could be included in a psychiatric review of systems, thus potentially improving the detection of BPD. Researchers hypothesized that affective instability, considered first by Linehan⁵³ and later by other theorists⁵⁴ to be of central importance to the clinical manifestations of BPD, could function as a gate criterion. In the sample of 3,674 psychiatric outpatients who were evaluated with a semi-structured interview, the sensitivity of the affective instability criterion was 92.8%, and the negative predictive value of the criterion was 99%.