Bipolar Disorder

People with remitted bipolar I disorder appear to show lower rather than higher activity in the ventral striatum in anticipation of monetary gains, compared with controls, results of a small study suggest. In addition, associations were found between positive urgency measure (PUM) and blunted activity in the nucleus accumbens in individuals with bipolar I.

“Together, these findings suggest that individuals with remitted bipolar disorder show blunted ventral striatal responses during anticipation of conventional rewards (e.g., money),” wrote lead author Sheri L. Johnson, PhD, and associates. The study was published in Neuroimage: Clinical.

Dr. Johnson’s team recruited the participants through advertisements online and in the community. Their study included 24 people with bipolar I (14 men; mean age, 36.22 years) and 24 controls without bipolar (13 men; mean age, 33.92 years), reported Dr. Johnson, of the University of California, Berkeley, and associates. The investigators used a version of the Monetary Incentive Delay Task to elicit neural and behavioral responses and their outcomes during fMRI.

Whole brain analyses found that, compared with the control group, those in the bipolar group “showed less activity for the gain anticipation contrast specifically in the ventral striatum (including the right [nucleus accumbens] and right globus pallidus), as well as less activity for the gain outcome contrast in the left occipital gyrus,” the investigators wrote.

PUM, a dimensional trait, was designed to assess tendencies to act “regrettably” or “impulsively” during states of positive emotion. PUM scores have been correlated with outcomes such as lower functioning in behavior, decreased quality of life, and worse outcomes in bipolar disorder. The investigators hoped that, by including PUM to help evaluate group differences, they could account for inconsistent findings regarding associations of neural imaging and reward responses.

“The findings associate for the first time a behavioral measure of PUM ... with neural anomalies in reward processing,” they wrote. “The current findings imply that, in individuals with bipolar disorder, individual differences in PUM may also help account for blunted [nucleus accumbens] during reward anticipation.”

The study’s sample size limited the power to detect small effects or interactions. The researchers felt, though, that the sample was well matched and adequately powered for the primary variables of interest.

The authors had no conflicts of interest to disclose. The study was funded by a grant from the National Institute of Mental Health.

[email protected]

SOURCE: Johnson SL et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2019.102018.

People with remitted bipolar I disorder appear to show lower rather than higher activity in the ventral striatum in anticipation of monetary gains, compared with controls, results of a small study suggest. In addition, associations were found between positive urgency measure (PUM) and blunted activity in the nucleus accumbens in individuals with bipolar I.

“Together, these findings suggest that individuals with remitted bipolar disorder show blunted ventral striatal responses during anticipation of conventional rewards (e.g., money),” wrote lead author Sheri L. Johnson, PhD, and associates. The study was published in Neuroimage: Clinical.

Dr. Johnson’s team recruited the participants through advertisements online and in the community. Their study included 24 people with bipolar I (14 men; mean age, 36.22 years) and 24 controls without bipolar (13 men; mean age, 33.92 years), reported Dr. Johnson, of the University of California, Berkeley, and associates. The investigators used a version of the Monetary Incentive Delay Task to elicit neural and behavioral responses and their outcomes during fMRI.

Whole brain analyses found that, compared with the control group, those in the bipolar group “showed less activity for the gain anticipation contrast specifically in the ventral striatum (including the right [nucleus accumbens] and right globus pallidus), as well as less activity for the gain outcome contrast in the left occipital gyrus,” the investigators wrote.

PUM, a dimensional trait, was designed to assess tendencies to act “regrettably” or “impulsively” during states of positive emotion. PUM scores have been correlated with outcomes such as lower functioning in behavior, decreased quality of life, and worse outcomes in bipolar disorder. The investigators hoped that, by including PUM to help evaluate group differences, they could account for inconsistent findings regarding associations of neural imaging and reward responses.

“The findings associate for the first time a behavioral measure of PUM ... with neural anomalies in reward processing,” they wrote. “The current findings imply that, in individuals with bipolar disorder, individual differences in PUM may also help account for blunted [nucleus accumbens] during reward anticipation.”

The study’s sample size limited the power to detect small effects or interactions. The researchers felt, though, that the sample was well matched and adequately powered for the primary variables of interest.

The authors had no conflicts of interest to disclose. The study was funded by a grant from the National Institute of Mental Health.

[email protected]

SOURCE: Johnson SL et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2019.102018.

People with remitted bipolar I disorder appear to show lower rather than higher activity in the ventral striatum in anticipation of monetary gains, compared with controls, results of a small study suggest. In addition, associations were found between positive urgency measure (PUM) and blunted activity in the nucleus accumbens in individuals with bipolar I.

“Together, these findings suggest that individuals with remitted bipolar disorder show blunted ventral striatal responses during anticipation of conventional rewards (e.g., money),” wrote lead author Sheri L. Johnson, PhD, and associates. The study was published in Neuroimage: Clinical.

Dr. Johnson’s team recruited the participants through advertisements online and in the community. Their study included 24 people with bipolar I (14 men; mean age, 36.22 years) and 24 controls without bipolar (13 men; mean age, 33.92 years), reported Dr. Johnson, of the University of California, Berkeley, and associates. The investigators used a version of the Monetary Incentive Delay Task to elicit neural and behavioral responses and their outcomes during fMRI.

Whole brain analyses found that, compared with the control group, those in the bipolar group “showed less activity for the gain anticipation contrast specifically in the ventral striatum (including the right [nucleus accumbens] and right globus pallidus), as well as less activity for the gain outcome contrast in the left occipital gyrus,” the investigators wrote.

PUM, a dimensional trait, was designed to assess tendencies to act “regrettably” or “impulsively” during states of positive emotion. PUM scores have been correlated with outcomes such as lower functioning in behavior, decreased quality of life, and worse outcomes in bipolar disorder. The investigators hoped that, by including PUM to help evaluate group differences, they could account for inconsistent findings regarding associations of neural imaging and reward responses.

“The findings associate for the first time a behavioral measure of PUM ... with neural anomalies in reward processing,” they wrote. “The current findings imply that, in individuals with bipolar disorder, individual differences in PUM may also help account for blunted [nucleus accumbens] during reward anticipation.”

The study’s sample size limited the power to detect small effects or interactions. The researchers felt, though, that the sample was well matched and adequately powered for the primary variables of interest.

The authors had no conflicts of interest to disclose. The study was funded by a grant from the National Institute of Mental Health.

[email protected]

SOURCE: Johnson SL et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2019.102018.

COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).

Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.

These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).

These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
 

Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?

Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.

“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.

He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.

Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).

“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.

“A different and perhaps more helpful way to think about it is to say good sleep is a resilience factor and puts you at lower risk of developing bipolar disorder,” he added.

Dr. Ritter reported having no financial conflicts regarding these studies.

[email protected]

COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).

Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.

These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).

These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
 

Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?

Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.

“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.

He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.

Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).

“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.

“A different and perhaps more helpful way to think about it is to say good sleep is a resilience factor and puts you at lower risk of developing bipolar disorder,” he added.

Dr. Ritter reported having no financial conflicts regarding these studies.

[email protected]

COPENHAGEN – Sleep spindle density is diminished in euthymic patients with bipolar disorder, suggesting that this sleep architecture abnormality might offer potential for early differentiation of bipolar from unipolar depression, Philipp S. Ritter, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“Hopefully in the future our finding, if replicated, might have clinical utility. It might be a kind of soft biomarker that could be used in early detection, or, in people having their first depressive episode, you could perhaps use this to risk-stratify. And if you see there’s a great reduction in spindle density then a patient might have a higher likelihood of a bipolar disorder, so you might not want to treat with antidepressants that have a high switch rate,” explained Dr. Ritter, a psychiatrist at Technical University of Dresden (Germany).

Sleep spindles are a specific sleep architecture formation evident on the sleep EEG. They are sudden high-amplitude bursts occurring in stage N2 sleep. They are thought to be associated with sensory gating and memory processes. Other investigators have repeatedly demonstrated that patients with schizophrenia, as well as their asymptomatic first-degree relatives, have a reduced density of fast spindles greater than 13 Hz, compared with the general population. In contrast, patients with unipolar depression do not display this polysomnographic abnormality.

These findings prompted Dr. Ritter and his coinvestigators to conduct an all-night polysomnographic study in 24 euthymic patients with bipolar disorder and 25 healthy controls. The bipolar patients demonstrated a reduced density and mean frequency of fast sleep spindles, but not slow spindles (Acta Psychiatr Scand. 2018 Aug;138[2]:163-72).

These sleep spindle findings implicate thalamic dysfunction as a potential neurobiologic mechanism in bipolar disorder, since spindles are generated in the thalamus and spun off in thalamocortical feedback loops, Dr. Ritter observed.
 

Which came first: the chicken (bipolar disorder) or the egg (sleep disturbance)?

Sleep problems are a prominent issue in patients with bipolar disorder, even when they are euthymic.

“Anybody who deals with bipolar patients knows that sleep is a constant issue. You are always talking to your patients about their sleep. They’re sleeping too much, or not enough, or they’re sleeping just about right but it’s unsatisfactory. They do not sleep well. And if there’s something that disrupts their sleep, it can precipitate episodes,” Dr. Ritter said.

He wondered whether sleep problems are an intrinsic part of the bipolar illness, or a byproduct of the stress of having a severe mental disorder, perhaps a medication side effect, or whether the disordered sleep actually precedes the clinical expression of the mood disorder. So he and his coinvestigators turned to a Munich-based cohort sample of 3,021 adolescents and young adults assessed via the standardized Composite International Diagnostic Interview four times during 10 years of prospective follow-up.

Among 1,943 participants in the epidemiologic study who were free of major mental disorders at entry, the presence of sleep disturbance at baseline as quantified using the Symptom Checklist-90-Revised doubled the risk of developing bipolar disorder within the next 10 years. After the researchers controlled for potential confounders, including parental mood disorder, gender, age, and a history of alcohol or cannabis dependence, poor sleep quality at baseline remained independently associated with a 1.75-fold increased chance of subsequently developing bipolar disorder (J Psychiatr Res. 2015 Sep;68:76-82).

“This is a little bit higher, actually, than the odds ratio usually found for depressive disorders,” said Dr. Ritter.

“A different and perhaps more helpful way to think about it is to say good sleep is a resilience factor and puts you at lower risk of developing bipolar disorder,” he added.

Dr. Ritter reported having no financial conflicts regarding these studies.

[email protected]

Blood-brain barrier imaging can serve as a biomarker for progression of disease in adults with bipolar disorder, results from a small study suggest.

“While the pathophysiology of bipolar disorder remains poorly understood, converging evidence points to the presence of neuroinflammation in bipolar patients,” wrote Lyna Kamintsky, a PhD candidate at Dalhousie University, Halifax, N.S., and colleagues.

The researchers examined MRI data from 36 patients with bipolar disorder and compared them with 14 matched controls. The average age of the patients was 49 years and the average duration of illness was 28 years. The study was published in NeuroImage: Clinical (2019 Oct 22. doi: 10.1016/j.nicl.2019.102049).

“Leakage rates were considered pathological when exceeding 0.02, the 95th percentile of all values in a cohort of control subjects,” the researchers said. Overall, 10 subjects (all patients with bipolar disorder) met criteria for “extensive blood-brain barrier leakage.” The researchers found that those patients also had higher rates of chronic illness, more frequent and/or severe manic episodes, and more severe anxiety, depression, and social/occupational dysfunction, compared with those without blood-brain barrier leakage.

The patients with extensive blood-brain barrier leakage also had higher body mass indexes, greater risk of cardiovascular disease, and advanced heart age. In addition, all patients in this group had comorbid insulin resistance.

The study findings were limited by the small sample size, but the results suggest that blood-brain barrier imaging could be a biomarker for bipolar disease progression with implications for treatment, the researchers said.

The study was supported by the European Union’s Seventh Framework Program, the Nova Scotia Health Research Foundation, Brain Canada, and the Brain & Behavior Research Foundation. The researchers disclosed having no financial conflicts.

SOURCE: Kamintsky L et al. NeuroImage: Clinical. 2019 Oct 22. doi: 10.1016/j.nicl.2019.102049.

Blood-brain barrier imaging can serve as a biomarker for progression of disease in adults with bipolar disorder, results from a small study suggest.

“While the pathophysiology of bipolar disorder remains poorly understood, converging evidence points to the presence of neuroinflammation in bipolar patients,” wrote Lyna Kamintsky, a PhD candidate at Dalhousie University, Halifax, N.S., and colleagues.

The researchers examined MRI data from 36 patients with bipolar disorder and compared them with 14 matched controls. The average age of the patients was 49 years and the average duration of illness was 28 years. The study was published in NeuroImage: Clinical (2019 Oct 22. doi: 10.1016/j.nicl.2019.102049).

“Leakage rates were considered pathological when exceeding 0.02, the 95th percentile of all values in a cohort of control subjects,” the researchers said. Overall, 10 subjects (all patients with bipolar disorder) met criteria for “extensive blood-brain barrier leakage.” The researchers found that those patients also had higher rates of chronic illness, more frequent and/or severe manic episodes, and more severe anxiety, depression, and social/occupational dysfunction, compared with those without blood-brain barrier leakage.

The patients with extensive blood-brain barrier leakage also had higher body mass indexes, greater risk of cardiovascular disease, and advanced heart age. In addition, all patients in this group had comorbid insulin resistance.

The study findings were limited by the small sample size, but the results suggest that blood-brain barrier imaging could be a biomarker for bipolar disease progression with implications for treatment, the researchers said.

The study was supported by the European Union’s Seventh Framework Program, the Nova Scotia Health Research Foundation, Brain Canada, and the Brain & Behavior Research Foundation. The researchers disclosed having no financial conflicts.

SOURCE: Kamintsky L et al. NeuroImage: Clinical. 2019 Oct 22. doi: 10.1016/j.nicl.2019.102049.

Blood-brain barrier imaging can serve as a biomarker for progression of disease in adults with bipolar disorder, results from a small study suggest.

“While the pathophysiology of bipolar disorder remains poorly understood, converging evidence points to the presence of neuroinflammation in bipolar patients,” wrote Lyna Kamintsky, a PhD candidate at Dalhousie University, Halifax, N.S., and colleagues.

The researchers examined MRI data from 36 patients with bipolar disorder and compared them with 14 matched controls. The average age of the patients was 49 years and the average duration of illness was 28 years. The study was published in NeuroImage: Clinical (2019 Oct 22. doi: 10.1016/j.nicl.2019.102049).

“Leakage rates were considered pathological when exceeding 0.02, the 95th percentile of all values in a cohort of control subjects,” the researchers said. Overall, 10 subjects (all patients with bipolar disorder) met criteria for “extensive blood-brain barrier leakage.” The researchers found that those patients also had higher rates of chronic illness, more frequent and/or severe manic episodes, and more severe anxiety, depression, and social/occupational dysfunction, compared with those without blood-brain barrier leakage.

The patients with extensive blood-brain barrier leakage also had higher body mass indexes, greater risk of cardiovascular disease, and advanced heart age. In addition, all patients in this group had comorbid insulin resistance.

The study findings were limited by the small sample size, but the results suggest that blood-brain barrier imaging could be a biomarker for bipolar disease progression with implications for treatment, the researchers said.

The study was supported by the European Union’s Seventh Framework Program, the Nova Scotia Health Research Foundation, Brain Canada, and the Brain & Behavior Research Foundation. The researchers disclosed having no financial conflicts.

SOURCE: Kamintsky L et al. NeuroImage: Clinical. 2019 Oct 22. doi: 10.1016/j.nicl.2019.102049.

Differences in self-reported and EEG-measured responses to emotional scenes between patients with bipolar I disorder with and without a history of psychosis, and healthy controls are negligible, results of a cross-sectional study suggest.

“While prior research supports abnormalities in the emotional face response, this study suggests these neural and behavior differences do not fully generalize to scenes, indicating that nonsocial emotional responding may be intact in these patients,” reported Rebekah L. Trotti and colleagues.

The investigators conducted a multisite study among 130 participants with bipolar and a history of psychosis, 75 with bipolar and no history of psychosis, and 181 healthy controls. Although the investigators had hypothesized that, in keeping with findings from face-processing studies, emotional responses would be reduced in patients with bipolar I disorder, they found no differences on EEG in early posterior negativity and only small differences for late positive potential between the groups. The groups were presented with the same 60 scenes that were unpleasant, neutral, or pleasant. The study was published in the Journal of Psychiatric Research.

Participants rated each scene according to the Self-Assessment Manikin after the respective EEG readings were taken. No significant statistical differences were seen on these ratings between groups, reported Ms. Trotti, a graduate student in the behavioral and brain sciences program at the University of Georgia, Athens, and colleagues.

The investigators also assessed whether participants had psychosis and looked at medications they were taking. However, those analyses also showed no statistically significant differences between participants with bipolar I and a history of psychosis, those with bipolar and no history of psychosis, and healthy controls in the processing of emotional scenes. Ms. Trotti and colleagues noted that other ways of differentiating subtypes in this heterogeneous disorder, such as those based on biomarkers and brain structure rather than those laid out by the DSM, might yield the differences in neural activity they had expected.

“Future research on this topic should focus on neurocognitive subtypes of mood and psychotic disorders, as well as other domains of emotional responding and behavior,” Ms. Trotti and colleagues wrote.

[email protected]

SOURCE: Trotti RL et al. J Psychiatr Res. 2019. doi: 10.1016/j.jpsychires.2019.10.005.

Differences in self-reported and EEG-measured responses to emotional scenes between patients with bipolar I disorder with and without a history of psychosis, and healthy controls are negligible, results of a cross-sectional study suggest.

“While prior research supports abnormalities in the emotional face response, this study suggests these neural and behavior differences do not fully generalize to scenes, indicating that nonsocial emotional responding may be intact in these patients,” reported Rebekah L. Trotti and colleagues.

The investigators conducted a multisite study among 130 participants with bipolar and a history of psychosis, 75 with bipolar and no history of psychosis, and 181 healthy controls. Although the investigators had hypothesized that, in keeping with findings from face-processing studies, emotional responses would be reduced in patients with bipolar I disorder, they found no differences on EEG in early posterior negativity and only small differences for late positive potential between the groups. The groups were presented with the same 60 scenes that were unpleasant, neutral, or pleasant. The study was published in the Journal of Psychiatric Research.

Participants rated each scene according to the Self-Assessment Manikin after the respective EEG readings were taken. No significant statistical differences were seen on these ratings between groups, reported Ms. Trotti, a graduate student in the behavioral and brain sciences program at the University of Georgia, Athens, and colleagues.

The investigators also assessed whether participants had psychosis and looked at medications they were taking. However, those analyses also showed no statistically significant differences between participants with bipolar I and a history of psychosis, those with bipolar and no history of psychosis, and healthy controls in the processing of emotional scenes. Ms. Trotti and colleagues noted that other ways of differentiating subtypes in this heterogeneous disorder, such as those based on biomarkers and brain structure rather than those laid out by the DSM, might yield the differences in neural activity they had expected.

“Future research on this topic should focus on neurocognitive subtypes of mood and psychotic disorders, as well as other domains of emotional responding and behavior,” Ms. Trotti and colleagues wrote.

[email protected]

SOURCE: Trotti RL et al. J Psychiatr Res. 2019. doi: 10.1016/j.jpsychires.2019.10.005.

Differences in self-reported and EEG-measured responses to emotional scenes between patients with bipolar I disorder with and without a history of psychosis, and healthy controls are negligible, results of a cross-sectional study suggest.

“While prior research supports abnormalities in the emotional face response, this study suggests these neural and behavior differences do not fully generalize to scenes, indicating that nonsocial emotional responding may be intact in these patients,” reported Rebekah L. Trotti and colleagues.

The investigators conducted a multisite study among 130 participants with bipolar and a history of psychosis, 75 with bipolar and no history of psychosis, and 181 healthy controls. Although the investigators had hypothesized that, in keeping with findings from face-processing studies, emotional responses would be reduced in patients with bipolar I disorder, they found no differences on EEG in early posterior negativity and only small differences for late positive potential between the groups. The groups were presented with the same 60 scenes that were unpleasant, neutral, or pleasant. The study was published in the Journal of Psychiatric Research.

Participants rated each scene according to the Self-Assessment Manikin after the respective EEG readings were taken. No significant statistical differences were seen on these ratings between groups, reported Ms. Trotti, a graduate student in the behavioral and brain sciences program at the University of Georgia, Athens, and colleagues.

The investigators also assessed whether participants had psychosis and looked at medications they were taking. However, those analyses also showed no statistically significant differences between participants with bipolar I and a history of psychosis, those with bipolar and no history of psychosis, and healthy controls in the processing of emotional scenes. Ms. Trotti and colleagues noted that other ways of differentiating subtypes in this heterogeneous disorder, such as those based on biomarkers and brain structure rather than those laid out by the DSM, might yield the differences in neural activity they had expected.

“Future research on this topic should focus on neurocognitive subtypes of mood and psychotic disorders, as well as other domains of emotional responding and behavior,” Ms. Trotti and colleagues wrote.

[email protected]

SOURCE: Trotti RL et al. J Psychiatr Res. 2019. doi: 10.1016/j.jpsychires.2019.10.005.

In our experience, most psychiatrists are uncomfortable with prescribing a medication when they feel that doing so would be outside their scope of practice. But there are many situations when prescribing a nonpsychotropic medication would be the correct choice. In this article, we discuss the scope of psychiatric practice, and present 4 case studies that illustrate situations in which psychiatrists should feel comfortable prescribing nonpsychotropic medications.

Defining the scope of practice

What is the scope of a psychiatrist’s practice? Scope of practice usually describes activities that a health care practitioner is allowed to undertake as defined by the terms of his/her license. A license to practice medicine does not include any stipulation restricting practice to a specific medical specialty. However, a local entity may delineate scope of practice within its organization. For instance, local practice standards held by the Detroit Wayne Mental Health Authority (DWMHA) state “Psychiatrists…shall not exceed their scope of practice as per DWMHA credentialing and privileging. For example, a Psychiatrist…who [has] not been appropriately privileged to deliver services to children shall not treat children, excepting crisis situations.”¹

Like physicians in other specialties, psychiatrists are not limited to prescribing only a subset of medications commonly associated with their specialty. But for many psychiatrists, prescribing nonpsychotropic medications is complicated by individual and local factors. On one hand, some psychiatrists do not feel it is their role to prescribe nonpsychotropic medications,² or even some psychotropic medications that may be more complex to prescribe, such as lithium, clozapine, or monoamine oxidase inhibitors.^3-5 However, many feel comfortable prescribing complex combinations of psychotropic medications, or prescribing in a way that does not necessarily make sense (eg, prescribing benztropine as prophylaxis for dystonia when starting an antipsychotic).

Reviewing an average day at one urban psychiatric clinic, these questions seem to come up in half of the patient population, especially in patients with chronic mental illness, multiple medical comorbidities, and limited access to health care. When a young patient walks in without an appointment with an acute dystonic reaction secondary to the initiation of antipsychotics a couple of days ago, there is no hesitation to swiftly and appropriately prescribe an IM anticholinergic medication. But why are psychiatrists often hesitant to prescribe nonpsychotropic medications to treat other adverse effects of medications? Lack of knowledge? Lack of training?

Psychiatrists who practice in hospital systems often have immediate access to consultants, and this availability may encourage them to defer to the consultant for treatment of certain adverse effects. We have seen psychiatrists consult Neurology regarding the prescription of donepezil for mild neurocognitive disorder due to Alzheimer’s disease, or Endocrinology regarding prescription of levothyroxine for lithium-induced hypothyroidism.

However, there are numerous scenarios in which psychiatrists should feel comfortable prescribing nonpsychotropic medications or managing medication adverse effects, regardless of whether they consider it to be within or outside their scope of practice. The following case examples illustrate several such situations.

CASE 1

Ms. W, age 30, has been diagnosed with schizophrenia. She requests a refill of quetiapine, 800 mg/d. This medication has been clearly beneficial in alleviating her psychotic symptoms. However, since her last visit 3 months ago, her face appears more round, and she has gained 9 kg. Further evaluation indicates that she has developed metabolic syndrome and pre-diabetes.

Continue to: Metabolic adverse effects

Metabolic adverse effects, such as metabolic syndrome, diabetic ketoacidosis, and cardiovascular disease, are well-known risks of prescribing second-generation antipsychotics.⁶ In such situations, psychiatrists often advise patients to modify their diet, increase physical activity, and follow up with their primary care physician to determine if other medications are needed. However, getting a patient with a serious mental illness to exercise and modify her/his diet is difficult, and many of these patients do not have a primary care physician.

For patients such as Ms. W, a psychiatrist should consider prescribing metformin. Wu et al⁷ found that in addition to lifestyle modifications, metformin had the greatest effect on antipsychotic-induced weight gain. In this study, metformin alone had more impact on reversing weight gain and increasing insulin sensitivity than lifestyle modifications alone.⁷ This is crucial because these patients are especially vulnerable to cardiac disease.⁸ Metformin is well tolerated and has a low risk of causing hypoglycemia. Concerns regarding lactic acidosis have abated to the extent that the estimated glomerular filtration rate (eGFR) limits for using metformin have been lowered significantly. After reviewing the contraindications, the only knowledge needed to prescribe metformin is the patient’s kidney function and a brief understanding of the titration needed to minimize gastrointestinal adverse effects.⁹ Thus, prescribing metformin would be a fairly logical and easy first step for managing metabolic syndrome, especially in a patient whose motivation for increasing physical activity and modifying his/her diet is doubtful.

CASE 2

Mr. B, age 45, has major depressive disorder that has been well-controlled on paroxetine, 40 mg/d, for the past 2 years. He has no history of physical illness. On his most recent visit, he appears uncomfortable and nervous. After a long discussion, he discloses that his sex life isn’t what it used to be since starting paroxetine. He is bothered by erectile problems and asks whether he can “get some Viagra.”

Sexual adverse effects, such as erectile dysfunction, are frequently associated with the use of selective serotonin reuptake inhibitors.¹⁰ Although managing these adverse effects requires careful evaluation, in most cases, psychiatrists should be able to treat them.¹⁰ The logical choice in this case would be to prescribe one of the 4 FDA-approved phosphodiesterase-5 inhibitors (sildenafil [Viagra], tadalafil [Cialis], vardenafil [Levitra], and avanafil [Stendra]. However, Balon et al¹¹ found that few psychiatrists prescribe phosphodiesterase-5 inhibitors, although they believed that they should be prescribing to treat their patients’ sexual dysfunction. Managing these adverse effects is important not only for the patient’s quality of life and relationship with his/her partner, but also for the therapeutic alliance. In a systematic review of 23 trials, Taylor et al¹² examined >1,800 patients who were prescribed a medication to address sexual dysfunction secondary to antidepressants. They found that for men, adding a phosphodiesterase-5 inhibitor was appropriate and effective, and for women, adding bupropion at high doses should be considered.¹² Like many other adverse effects, sexual adverse effects surely play a role in medication compliance. Dording et al¹³ found that the addition of sildenafil, 50 to 100 mg as needed, resulted in increased treatment satisfaction and overall contentment in 102 patients who complained of sexual dysfunction in the follow-up phase of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) antidepressant trials. In most cases, with proper psychoeducation, prescription of phosphodiesterase-5 inhibitors is fairly straightforward.

CASE 3

Ms. G, age 22, was recently discharged from an inpatient psychiatric unit after an episode of mania. She was prescribed carbamazepine, 600 mg/d, and ziprasidone, 40 mg twice a day, and appears to be doing well on this regimen. When asked about what led to her admission, she recalls having an elevated mood, increased energy, hypersexuality, impulsivity, and poor judgment. She reveals that she had several sexual partners during her manic episode, and worries that if such behavior occurs again, she may get pregnant. Yet Ms. G was not prescribed birth control upon discharge.

Continue to: Contraception

Contraception. We believe that psychiatrists have an obligation to protect patients from consequences of mental illness. Much the same way that psychiatrists hope to prevent suicide in a patient who has depression, patients should be protected from risks encountered in the manic phase of bipolar disorder. Another reason to prescribe contraceptives in such patients is the teratogenic effects of mood stabilizers. Pagano et al¹⁴ reviewed 6 studies that examined common forms of hormonal birth control to determine their safety in patients with depression or bipolar disorder. They found that overall, use of hormonal contraception was not associated with a worse clinical course of disease.

Many available forms of birth control are available. When prescribing in an outpatient setting, a daily oral medication or a monthly depot injection are convenient options.

CASE 4

Mr. P, age 65, has bipolar I disorder and is stable on risperidone long-acting injection, 37.7 mg bimonthly, and lithium, 1,200 mg/d. He reports that he is doing well but has noticed a recent decrease in energy and weight gain without any change in mood. Laboratory testing conducted prior to this visit revealed a thyroid-stimulating hormone (TSH) level of 4 mU/L (normal range: 0.4 to 4.0 mU/L). Six months ago, Mr. P’s TSH level was 2.8 mU/L. The resident supervisor suggests discussing the case with an endocrinologist.

Thyroid function. The impact of lithium on the thyroid gland is well established; however, psychiatrists’ response to such changes are not.¹⁵ Gitlin¹⁶ reviewed the many adverse effects of lithium and presented various management strategies to address findings such as Mr. P’s. Two important points are that lithium should not be discontinued in light of hypothyroidism, and synthetic thyroxine (levothyroxine) can be initiated and titrated to return TSH levels to a normal range.¹⁶ Levothyroxine can be started at low doses (eg, 25 to 50 mcg/d) and increased every 6 weeks until a normal TSH level is achieved.¹⁷ Managing lithium-induced clinical or subclinical hypothyroidism can prevent further pathology and possible relapse to depression.

Incorporating integrated care

In all these cases, the prescription of a medication with which some psychiatrists are not comfortable prescribing would have been the logical, easiest, and preferable choice. Of course, when initiating any medication, boxed warnings, contraindications, and drug–drug interactions should be reviewed. Initial dosages and titration schedules can be found in every medication’s FDA-approved prescribing information document (package insert), as well as in numerous reference books and articles.

Continue to: We acknowledge...

We acknowledge that prescribing a nonpsychotropic medication is not always a psychiatrist’s best choice, and that in patients with multiple medical comorbidities and drug–drug interactions that are not clearly defined, referring to or consulting a specialist is appropriate. We in no way support reckless prescribing, but instead present an opportunity to expand the perception of what should be considered within a psychiatrist’s scope of practice, and call for further education of psychiatrists so that they are more comfortable managing these adverse effects and/or prescribing at least some nonpsychotropic medications. For example, metabolic syndrome, uncomplicated hypertension, and hypothyroidism (not necessarily lithium-induced) could be managed by psychiatrists practicing integrated care (Table).

We exhort integrated medical care during this time of a physician shortage; however, we do not practice this way. Interestingly, physicians in primary care, such as those in family medicine or obstetrics and gynecology, frequently attempt to treat patients with psychiatric conditions in an attempt to provide integrated care. Numerous articles have discussed these efforts.^18-20 However, this type of integrated care seems less frequent in psychiatry, even though the practice of modern psychiatry in the United States shows substantial overlap with the practice of physicians in primary care specialties.²¹ There are few articles or practical guidelines for psychiatrists who wish to treat patients’ physical illnesses, particularly patients with severe mental illness (see Related Resources, page 56). If we practice in an integrated manner to treat one of the simple conditions we described above, we can eliminate the need for a patient to visit a second physician, pay another co-pay, pay another bus fare, and take another day off work. This can be particularly helpful for patients who at times have to decide between paying for groceries or for medications. Having one clinician manage a patient’s medications also can decrease the risk of polypharmacy.

In addition to the case scenarios described in this article, there are more clinical situations and nonpsychotropic medications that psychiatrists could manage. Considering them outside the scope of psychiatric practice and being uncomfortable or ambivalent about them is not an excuse. We hope that psychiatrists can increase their expertise in this area, and can start to practice as the primary care physicians they claim they are, and should be.

Bottom Line

Many psychiatrists are uncomfortable prescribing nonpsychotropic medications, but there are numerous clinical scenarios in which the practice would make sense. This could include cases of metabolic syndrome, sexual dysfunction secondary to antidepressant use, or other adverse effects of commonly prescribed psychotropic medications.

Related Resources

• McCarron RM, Xiong GL, Keenan CR, et al. Preventive medical care in psychiatry. A practical guide for clinicians. Arlington, VA: American Psychiatric Association Publishing; 2015.
• McCarron RM, Xiong GL, Keenan CR, et al. Study guide to preventive medical care in psychiatry. Arlington, VA: American Psychiatric Association Publishing; 2017.
• Goldberg JF, Ernst CL. Managing the side effects of psychotropic medications. Washington, DC: American Psychiatric Association Publishing; 2019.

Drug Brand Names

Avanafil • Stendra
Benztropine • Cogentin
Bupropion • Wellbutrin, Zyban
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Levothyroxine • Levoxyl, Synthroid
Lithium • Eskalith, Lithobid
Metformin • Fortamet, Glucophage
Paroxetine • Paxil
Quetiapine • Seroquel
Risperidone long-acting injection • Risperdal Consta
Sildenafil • Viagra
Tadalafil • Cialis
Vardenafil • Levitra
Ziprasidone • Geodon

In our experience, most psychiatrists are uncomfortable with prescribing a medication when they feel that doing so would be outside their scope of practice. But there are many situations when prescribing a nonpsychotropic medication would be the correct choice. In this article, we discuss the scope of psychiatric practice, and present 4 case studies that illustrate situations in which psychiatrists should feel comfortable prescribing nonpsychotropic medications.

Defining the scope of practice

What is the scope of a psychiatrist’s practice? Scope of practice usually describes activities that a health care practitioner is allowed to undertake as defined by the terms of his/her license. A license to practice medicine does not include any stipulation restricting practice to a specific medical specialty. However, a local entity may delineate scope of practice within its organization. For instance, local practice standards held by the Detroit Wayne Mental Health Authority (DWMHA) state “Psychiatrists…shall not exceed their scope of practice as per DWMHA credentialing and privileging. For example, a Psychiatrist…who [has] not been appropriately privileged to deliver services to children shall not treat children, excepting crisis situations.”¹

Like physicians in other specialties, psychiatrists are not limited to prescribing only a subset of medications commonly associated with their specialty. But for many psychiatrists, prescribing nonpsychotropic medications is complicated by individual and local factors. On one hand, some psychiatrists do not feel it is their role to prescribe nonpsychotropic medications,² or even some psychotropic medications that may be more complex to prescribe, such as lithium, clozapine, or monoamine oxidase inhibitors.^3-5 However, many feel comfortable prescribing complex combinations of psychotropic medications, or prescribing in a way that does not necessarily make sense (eg, prescribing benztropine as prophylaxis for dystonia when starting an antipsychotic).

Reviewing an average day at one urban psychiatric clinic, these questions seem to come up in half of the patient population, especially in patients with chronic mental illness, multiple medical comorbidities, and limited access to health care. When a young patient walks in without an appointment with an acute dystonic reaction secondary to the initiation of antipsychotics a couple of days ago, there is no hesitation to swiftly and appropriately prescribe an IM anticholinergic medication. But why are psychiatrists often hesitant to prescribe nonpsychotropic medications to treat other adverse effects of medications? Lack of knowledge? Lack of training?

Psychiatrists who practice in hospital systems often have immediate access to consultants, and this availability may encourage them to defer to the consultant for treatment of certain adverse effects. We have seen psychiatrists consult Neurology regarding the prescription of donepezil for mild neurocognitive disorder due to Alzheimer’s disease, or Endocrinology regarding prescription of levothyroxine for lithium-induced hypothyroidism.

However, there are numerous scenarios in which psychiatrists should feel comfortable prescribing nonpsychotropic medications or managing medication adverse effects, regardless of whether they consider it to be within or outside their scope of practice. The following case examples illustrate several such situations.

CASE 1

Ms. W, age 30, has been diagnosed with schizophrenia. She requests a refill of quetiapine, 800 mg/d. This medication has been clearly beneficial in alleviating her psychotic symptoms. However, since her last visit 3 months ago, her face appears more round, and she has gained 9 kg. Further evaluation indicates that she has developed metabolic syndrome and pre-diabetes.

Continue to: Metabolic adverse effects

Metabolic adverse effects, such as metabolic syndrome, diabetic ketoacidosis, and cardiovascular disease, are well-known risks of prescribing second-generation antipsychotics.⁶ In such situations, psychiatrists often advise patients to modify their diet, increase physical activity, and follow up with their primary care physician to determine if other medications are needed. However, getting a patient with a serious mental illness to exercise and modify her/his diet is difficult, and many of these patients do not have a primary care physician.

For patients such as Ms. W, a psychiatrist should consider prescribing metformin. Wu et al⁷ found that in addition to lifestyle modifications, metformin had the greatest effect on antipsychotic-induced weight gain. In this study, metformin alone had more impact on reversing weight gain and increasing insulin sensitivity than lifestyle modifications alone.⁷ This is crucial because these patients are especially vulnerable to cardiac disease.⁸ Metformin is well tolerated and has a low risk of causing hypoglycemia. Concerns regarding lactic acidosis have abated to the extent that the estimated glomerular filtration rate (eGFR) limits for using metformin have been lowered significantly. After reviewing the contraindications, the only knowledge needed to prescribe metformin is the patient’s kidney function and a brief understanding of the titration needed to minimize gastrointestinal adverse effects.⁹ Thus, prescribing metformin would be a fairly logical and easy first step for managing metabolic syndrome, especially in a patient whose motivation for increasing physical activity and modifying his/her diet is doubtful.

CASE 2

Mr. B, age 45, has major depressive disorder that has been well-controlled on paroxetine, 40 mg/d, for the past 2 years. He has no history of physical illness. On his most recent visit, he appears uncomfortable and nervous. After a long discussion, he discloses that his sex life isn’t what it used to be since starting paroxetine. He is bothered by erectile problems and asks whether he can “get some Viagra.”

Sexual adverse effects, such as erectile dysfunction, are frequently associated with the use of selective serotonin reuptake inhibitors.¹⁰ Although managing these adverse effects requires careful evaluation, in most cases, psychiatrists should be able to treat them.¹⁰ The logical choice in this case would be to prescribe one of the 4 FDA-approved phosphodiesterase-5 inhibitors (sildenafil [Viagra], tadalafil [Cialis], vardenafil [Levitra], and avanafil [Stendra]. However, Balon et al¹¹ found that few psychiatrists prescribe phosphodiesterase-5 inhibitors, although they believed that they should be prescribing to treat their patients’ sexual dysfunction. Managing these adverse effects is important not only for the patient’s quality of life and relationship with his/her partner, but also for the therapeutic alliance. In a systematic review of 23 trials, Taylor et al¹² examined >1,800 patients who were prescribed a medication to address sexual dysfunction secondary to antidepressants. They found that for men, adding a phosphodiesterase-5 inhibitor was appropriate and effective, and for women, adding bupropion at high doses should be considered.¹² Like many other adverse effects, sexual adverse effects surely play a role in medication compliance. Dording et al¹³ found that the addition of sildenafil, 50 to 100 mg as needed, resulted in increased treatment satisfaction and overall contentment in 102 patients who complained of sexual dysfunction in the follow-up phase of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) antidepressant trials. In most cases, with proper psychoeducation, prescription of phosphodiesterase-5 inhibitors is fairly straightforward.

CASE 3

Ms. G, age 22, was recently discharged from an inpatient psychiatric unit after an episode of mania. She was prescribed carbamazepine, 600 mg/d, and ziprasidone, 40 mg twice a day, and appears to be doing well on this regimen. When asked about what led to her admission, she recalls having an elevated mood, increased energy, hypersexuality, impulsivity, and poor judgment. She reveals that she had several sexual partners during her manic episode, and worries that if such behavior occurs again, she may get pregnant. Yet Ms. G was not prescribed birth control upon discharge.

Continue to: Contraception

Contraception. We believe that psychiatrists have an obligation to protect patients from consequences of mental illness. Much the same way that psychiatrists hope to prevent suicide in a patient who has depression, patients should be protected from risks encountered in the manic phase of bipolar disorder. Another reason to prescribe contraceptives in such patients is the teratogenic effects of mood stabilizers. Pagano et al¹⁴ reviewed 6 studies that examined common forms of hormonal birth control to determine their safety in patients with depression or bipolar disorder. They found that overall, use of hormonal contraception was not associated with a worse clinical course of disease.

Many available forms of birth control are available. When prescribing in an outpatient setting, a daily oral medication or a monthly depot injection are convenient options.

CASE 4

Mr. P, age 65, has bipolar I disorder and is stable on risperidone long-acting injection, 37.7 mg bimonthly, and lithium, 1,200 mg/d. He reports that he is doing well but has noticed a recent decrease in energy and weight gain without any change in mood. Laboratory testing conducted prior to this visit revealed a thyroid-stimulating hormone (TSH) level of 4 mU/L (normal range: 0.4 to 4.0 mU/L). Six months ago, Mr. P’s TSH level was 2.8 mU/L. The resident supervisor suggests discussing the case with an endocrinologist.

Thyroid function. The impact of lithium on the thyroid gland is well established; however, psychiatrists’ response to such changes are not.¹⁵ Gitlin¹⁶ reviewed the many adverse effects of lithium and presented various management strategies to address findings such as Mr. P’s. Two important points are that lithium should not be discontinued in light of hypothyroidism, and synthetic thyroxine (levothyroxine) can be initiated and titrated to return TSH levels to a normal range.¹⁶ Levothyroxine can be started at low doses (eg, 25 to 50 mcg/d) and increased every 6 weeks until a normal TSH level is achieved.¹⁷ Managing lithium-induced clinical or subclinical hypothyroidism can prevent further pathology and possible relapse to depression.

Incorporating integrated care

In all these cases, the prescription of a medication with which some psychiatrists are not comfortable prescribing would have been the logical, easiest, and preferable choice. Of course, when initiating any medication, boxed warnings, contraindications, and drug–drug interactions should be reviewed. Initial dosages and titration schedules can be found in every medication’s FDA-approved prescribing information document (package insert), as well as in numerous reference books and articles.

Continue to: We acknowledge...

We acknowledge that prescribing a nonpsychotropic medication is not always a psychiatrist’s best choice, and that in patients with multiple medical comorbidities and drug–drug interactions that are not clearly defined, referring to or consulting a specialist is appropriate. We in no way support reckless prescribing, but instead present an opportunity to expand the perception of what should be considered within a psychiatrist’s scope of practice, and call for further education of psychiatrists so that they are more comfortable managing these adverse effects and/or prescribing at least some nonpsychotropic medications. For example, metabolic syndrome, uncomplicated hypertension, and hypothyroidism (not necessarily lithium-induced) could be managed by psychiatrists practicing integrated care (Table).

We exhort integrated medical care during this time of a physician shortage; however, we do not practice this way. Interestingly, physicians in primary care, such as those in family medicine or obstetrics and gynecology, frequently attempt to treat patients with psychiatric conditions in an attempt to provide integrated care. Numerous articles have discussed these efforts.^18-20 However, this type of integrated care seems less frequent in psychiatry, even though the practice of modern psychiatry in the United States shows substantial overlap with the practice of physicians in primary care specialties.²¹ There are few articles or practical guidelines for psychiatrists who wish to treat patients’ physical illnesses, particularly patients with severe mental illness (see Related Resources, page 56). If we practice in an integrated manner to treat one of the simple conditions we described above, we can eliminate the need for a patient to visit a second physician, pay another co-pay, pay another bus fare, and take another day off work. This can be particularly helpful for patients who at times have to decide between paying for groceries or for medications. Having one clinician manage a patient’s medications also can decrease the risk of polypharmacy.

In addition to the case scenarios described in this article, there are more clinical situations and nonpsychotropic medications that psychiatrists could manage. Considering them outside the scope of psychiatric practice and being uncomfortable or ambivalent about them is not an excuse. We hope that psychiatrists can increase their expertise in this area, and can start to practice as the primary care physicians they claim they are, and should be.

Bottom Line

Many psychiatrists are uncomfortable prescribing nonpsychotropic medications, but there are numerous clinical scenarios in which the practice would make sense. This could include cases of metabolic syndrome, sexual dysfunction secondary to antidepressant use, or other adverse effects of commonly prescribed psychotropic medications.

Related Resources

• McCarron RM, Xiong GL, Keenan CR, et al. Preventive medical care in psychiatry. A practical guide for clinicians. Arlington, VA: American Psychiatric Association Publishing; 2015.
• McCarron RM, Xiong GL, Keenan CR, et al. Study guide to preventive medical care in psychiatry. Arlington, VA: American Psychiatric Association Publishing; 2017.
• Goldberg JF, Ernst CL. Managing the side effects of psychotropic medications. Washington, DC: American Psychiatric Association Publishing; 2019.

Drug Brand Names

Avanafil • Stendra
Benztropine • Cogentin
Bupropion • Wellbutrin, Zyban
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Levothyroxine • Levoxyl, Synthroid
Lithium • Eskalith, Lithobid
Metformin • Fortamet, Glucophage
Paroxetine • Paxil
Quetiapine • Seroquel
Risperidone long-acting injection • Risperdal Consta
Sildenafil • Viagra
Tadalafil • Cialis
Vardenafil • Levitra
Ziprasidone • Geodon

In our experience, most psychiatrists are uncomfortable with prescribing a medication when they feel that doing so would be outside their scope of practice. But there are many situations when prescribing a nonpsychotropic medication would be the correct choice. In this article, we discuss the scope of psychiatric practice, and present 4 case studies that illustrate situations in which psychiatrists should feel comfortable prescribing nonpsychotropic medications.

Defining the scope of practice

What is the scope of a psychiatrist’s practice? Scope of practice usually describes activities that a health care practitioner is allowed to undertake as defined by the terms of his/her license. A license to practice medicine does not include any stipulation restricting practice to a specific medical specialty. However, a local entity may delineate scope of practice within its organization. For instance, local practice standards held by the Detroit Wayne Mental Health Authority (DWMHA) state “Psychiatrists…shall not exceed their scope of practice as per DWMHA credentialing and privileging. For example, a Psychiatrist…who [has] not been appropriately privileged to deliver services to children shall not treat children, excepting crisis situations.”¹

Like physicians in other specialties, psychiatrists are not limited to prescribing only a subset of medications commonly associated with their specialty. But for many psychiatrists, prescribing nonpsychotropic medications is complicated by individual and local factors. On one hand, some psychiatrists do not feel it is their role to prescribe nonpsychotropic medications,² or even some psychotropic medications that may be more complex to prescribe, such as lithium, clozapine, or monoamine oxidase inhibitors.^3-5 However, many feel comfortable prescribing complex combinations of psychotropic medications, or prescribing in a way that does not necessarily make sense (eg, prescribing benztropine as prophylaxis for dystonia when starting an antipsychotic).

Reviewing an average day at one urban psychiatric clinic, these questions seem to come up in half of the patient population, especially in patients with chronic mental illness, multiple medical comorbidities, and limited access to health care. When a young patient walks in without an appointment with an acute dystonic reaction secondary to the initiation of antipsychotics a couple of days ago, there is no hesitation to swiftly and appropriately prescribe an IM anticholinergic medication. But why are psychiatrists often hesitant to prescribe nonpsychotropic medications to treat other adverse effects of medications? Lack of knowledge? Lack of training?

Psychiatrists who practice in hospital systems often have immediate access to consultants, and this availability may encourage them to defer to the consultant for treatment of certain adverse effects. We have seen psychiatrists consult Neurology regarding the prescription of donepezil for mild neurocognitive disorder due to Alzheimer’s disease, or Endocrinology regarding prescription of levothyroxine for lithium-induced hypothyroidism.

However, there are numerous scenarios in which psychiatrists should feel comfortable prescribing nonpsychotropic medications or managing medication adverse effects, regardless of whether they consider it to be within or outside their scope of practice. The following case examples illustrate several such situations.

CASE 1

Ms. W, age 30, has been diagnosed with schizophrenia. She requests a refill of quetiapine, 800 mg/d. This medication has been clearly beneficial in alleviating her psychotic symptoms. However, since her last visit 3 months ago, her face appears more round, and she has gained 9 kg. Further evaluation indicates that she has developed metabolic syndrome and pre-diabetes.

Continue to: Metabolic adverse effects

Metabolic adverse effects, such as metabolic syndrome, diabetic ketoacidosis, and cardiovascular disease, are well-known risks of prescribing second-generation antipsychotics.⁶ In such situations, psychiatrists often advise patients to modify their diet, increase physical activity, and follow up with their primary care physician to determine if other medications are needed. However, getting a patient with a serious mental illness to exercise and modify her/his diet is difficult, and many of these patients do not have a primary care physician.

For patients such as Ms. W, a psychiatrist should consider prescribing metformin. Wu et al⁷ found that in addition to lifestyle modifications, metformin had the greatest effect on antipsychotic-induced weight gain. In this study, metformin alone had more impact on reversing weight gain and increasing insulin sensitivity than lifestyle modifications alone.⁷ This is crucial because these patients are especially vulnerable to cardiac disease.⁸ Metformin is well tolerated and has a low risk of causing hypoglycemia. Concerns regarding lactic acidosis have abated to the extent that the estimated glomerular filtration rate (eGFR) limits for using metformin have been lowered significantly. After reviewing the contraindications, the only knowledge needed to prescribe metformin is the patient’s kidney function and a brief understanding of the titration needed to minimize gastrointestinal adverse effects.⁹ Thus, prescribing metformin would be a fairly logical and easy first step for managing metabolic syndrome, especially in a patient whose motivation for increasing physical activity and modifying his/her diet is doubtful.

CASE 2

Mr. B, age 45, has major depressive disorder that has been well-controlled on paroxetine, 40 mg/d, for the past 2 years. He has no history of physical illness. On his most recent visit, he appears uncomfortable and nervous. After a long discussion, he discloses that his sex life isn’t what it used to be since starting paroxetine. He is bothered by erectile problems and asks whether he can “get some Viagra.”

Sexual adverse effects, such as erectile dysfunction, are frequently associated with the use of selective serotonin reuptake inhibitors.¹⁰ Although managing these adverse effects requires careful evaluation, in most cases, psychiatrists should be able to treat them.¹⁰ The logical choice in this case would be to prescribe one of the 4 FDA-approved phosphodiesterase-5 inhibitors (sildenafil [Viagra], tadalafil [Cialis], vardenafil [Levitra], and avanafil [Stendra]. However, Balon et al¹¹ found that few psychiatrists prescribe phosphodiesterase-5 inhibitors, although they believed that they should be prescribing to treat their patients’ sexual dysfunction. Managing these adverse effects is important not only for the patient’s quality of life and relationship with his/her partner, but also for the therapeutic alliance. In a systematic review of 23 trials, Taylor et al¹² examined >1,800 patients who were prescribed a medication to address sexual dysfunction secondary to antidepressants. They found that for men, adding a phosphodiesterase-5 inhibitor was appropriate and effective, and for women, adding bupropion at high doses should be considered.¹² Like many other adverse effects, sexual adverse effects surely play a role in medication compliance. Dording et al¹³ found that the addition of sildenafil, 50 to 100 mg as needed, resulted in increased treatment satisfaction and overall contentment in 102 patients who complained of sexual dysfunction in the follow-up phase of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) antidepressant trials. In most cases, with proper psychoeducation, prescription of phosphodiesterase-5 inhibitors is fairly straightforward.

CASE 3

Ms. G, age 22, was recently discharged from an inpatient psychiatric unit after an episode of mania. She was prescribed carbamazepine, 600 mg/d, and ziprasidone, 40 mg twice a day, and appears to be doing well on this regimen. When asked about what led to her admission, she recalls having an elevated mood, increased energy, hypersexuality, impulsivity, and poor judgment. She reveals that she had several sexual partners during her manic episode, and worries that if such behavior occurs again, she may get pregnant. Yet Ms. G was not prescribed birth control upon discharge.

Continue to: Contraception

Contraception. We believe that psychiatrists have an obligation to protect patients from consequences of mental illness. Much the same way that psychiatrists hope to prevent suicide in a patient who has depression, patients should be protected from risks encountered in the manic phase of bipolar disorder. Another reason to prescribe contraceptives in such patients is the teratogenic effects of mood stabilizers. Pagano et al¹⁴ reviewed 6 studies that examined common forms of hormonal birth control to determine their safety in patients with depression or bipolar disorder. They found that overall, use of hormonal contraception was not associated with a worse clinical course of disease.

Many available forms of birth control are available. When prescribing in an outpatient setting, a daily oral medication or a monthly depot injection are convenient options.

CASE 4

Mr. P, age 65, has bipolar I disorder and is stable on risperidone long-acting injection, 37.7 mg bimonthly, and lithium, 1,200 mg/d. He reports that he is doing well but has noticed a recent decrease in energy and weight gain without any change in mood. Laboratory testing conducted prior to this visit revealed a thyroid-stimulating hormone (TSH) level of 4 mU/L (normal range: 0.4 to 4.0 mU/L). Six months ago, Mr. P’s TSH level was 2.8 mU/L. The resident supervisor suggests discussing the case with an endocrinologist.

Thyroid function. The impact of lithium on the thyroid gland is well established; however, psychiatrists’ response to such changes are not.¹⁵ Gitlin¹⁶ reviewed the many adverse effects of lithium and presented various management strategies to address findings such as Mr. P’s. Two important points are that lithium should not be discontinued in light of hypothyroidism, and synthetic thyroxine (levothyroxine) can be initiated and titrated to return TSH levels to a normal range.¹⁶ Levothyroxine can be started at low doses (eg, 25 to 50 mcg/d) and increased every 6 weeks until a normal TSH level is achieved.¹⁷ Managing lithium-induced clinical or subclinical hypothyroidism can prevent further pathology and possible relapse to depression.

Incorporating integrated care

In all these cases, the prescription of a medication with which some psychiatrists are not comfortable prescribing would have been the logical, easiest, and preferable choice. Of course, when initiating any medication, boxed warnings, contraindications, and drug–drug interactions should be reviewed. Initial dosages and titration schedules can be found in every medication’s FDA-approved prescribing information document (package insert), as well as in numerous reference books and articles.

Continue to: We acknowledge...

We acknowledge that prescribing a nonpsychotropic medication is not always a psychiatrist’s best choice, and that in patients with multiple medical comorbidities and drug–drug interactions that are not clearly defined, referring to or consulting a specialist is appropriate. We in no way support reckless prescribing, but instead present an opportunity to expand the perception of what should be considered within a psychiatrist’s scope of practice, and call for further education of psychiatrists so that they are more comfortable managing these adverse effects and/or prescribing at least some nonpsychotropic medications. For example, metabolic syndrome, uncomplicated hypertension, and hypothyroidism (not necessarily lithium-induced) could be managed by psychiatrists practicing integrated care (Table).

We exhort integrated medical care during this time of a physician shortage; however, we do not practice this way. Interestingly, physicians in primary care, such as those in family medicine or obstetrics and gynecology, frequently attempt to treat patients with psychiatric conditions in an attempt to provide integrated care. Numerous articles have discussed these efforts.^18-20 However, this type of integrated care seems less frequent in psychiatry, even though the practice of modern psychiatry in the United States shows substantial overlap with the practice of physicians in primary care specialties.²¹ There are few articles or practical guidelines for psychiatrists who wish to treat patients’ physical illnesses, particularly patients with severe mental illness (see Related Resources, page 56). If we practice in an integrated manner to treat one of the simple conditions we described above, we can eliminate the need for a patient to visit a second physician, pay another co-pay, pay another bus fare, and take another day off work. This can be particularly helpful for patients who at times have to decide between paying for groceries or for medications. Having one clinician manage a patient’s medications also can decrease the risk of polypharmacy.

In addition to the case scenarios described in this article, there are more clinical situations and nonpsychotropic medications that psychiatrists could manage. Considering them outside the scope of psychiatric practice and being uncomfortable or ambivalent about them is not an excuse. We hope that psychiatrists can increase their expertise in this area, and can start to practice as the primary care physicians they claim they are, and should be.

Bottom Line

Many psychiatrists are uncomfortable prescribing nonpsychotropic medications, but there are numerous clinical scenarios in which the practice would make sense. This could include cases of metabolic syndrome, sexual dysfunction secondary to antidepressant use, or other adverse effects of commonly prescribed psychotropic medications.

Related Resources

• McCarron RM, Xiong GL, Keenan CR, et al. Preventive medical care in psychiatry. A practical guide for clinicians. Arlington, VA: American Psychiatric Association Publishing; 2015.
• McCarron RM, Xiong GL, Keenan CR, et al. Study guide to preventive medical care in psychiatry. Arlington, VA: American Psychiatric Association Publishing; 2017.
• Goldberg JF, Ernst CL. Managing the side effects of psychotropic medications. Washington, DC: American Psychiatric Association Publishing; 2019.

Drug Brand Names

Avanafil • Stendra
Benztropine • Cogentin
Bupropion • Wellbutrin, Zyban
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Levothyroxine • Levoxyl, Synthroid
Lithium • Eskalith, Lithobid
Metformin • Fortamet, Glucophage
Paroxetine • Paxil
Quetiapine • Seroquel
Risperidone long-acting injection • Risperdal Consta
Sildenafil • Viagra
Tadalafil • Cialis
Vardenafil • Levitra
Ziprasidone • Geodon

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

Although evidence suggests that bipolar disorder (BD) and borderline personality disorder (BPD) are distinct entities, their differential diagnosis is often challenging as a result of considerable overlap of phenotypical features. Moreover, BD and BPD frequently co-occur, which makes it even more difficult to differentiate these 2 conditions. Strategies for improving diagnostic accuracy are critical to optimizing patients’ clinical outcomes and long-term prognosis. Misdiagnosing these 2 conditions can be particularly deleterious, and failure to recognize their co-occurrence can result in additional burden to typically complex and severe clinical presentations.

This article describes key aspects of the differential diagnosis between BD and BPD, emphasizing core features and major dissimilarities between these 2 conditions, and discusses the implications of misdiagnosis. The goal is to highlight the clinical and psychopathological aspects of BD and BPD to help clinicians properly distinguish these 2 disorders.

Psychopathological and sociodemographic correlates

Bipolar disorder is a chronic and severe mental illness that is classified based on clusters of symptoms—manic, hypomanic, and depressive.¹ It is among the 10 leading causes of disability worldwide, with significant morbidity arising from acute affective episodes and subacute states.² Data suggest the lifetime prevalence of BPD is 2.1%, and subthreshold forms may affect an additional 2.4% of the US population.³ The onset of symptoms typically occurs during late adolescence or early adulthood, and mood lability and cyclothymic temperament are the most common prodromal features.⁴

In contrast, personality disorders, such as BPD, are characteristically pervasive and maladaptive patterns of emotional responses that usually deviate from an individual’s stage of development and cultural background.¹ These disorders tend to cause significant impairment, particularly in personal, occupational, and social domains. Environmental factors, such as early childhood trauma, seem to play an important role in the genesis of personality disorders, which may be particularly relevant in BPD, a disorder characterized by marked impulsivity and a pattern of instability in personal relationships, self-image, and affect.^1,5,6 Similarly to BD, BPD is also chronic and highly disabling.

According to the National Survey on Alcohol and Related Conditions (NESARC), approximately 15% of US adults were found to have at least one type of personality disorder, and 6% met criteria for a cluster B personality disorder (antisocial, borderline, narcissistic, and histrionic).⁷ The lifetime prevalence of BPD is nearly 2%, with higher estimates observed in psychiatric settings.^7,8

As a result of the phenotypical resemblance between BD and BPD (Figure), the differential diagnosis is often difficult. Recent studies suggest that co-occurrence of BD and BPD is common, with rates of comorbid BPD as high as 29% in BD I and 24% in BD II.^8,9 On the other hand, nearly 20% of individuals with BPD seem to have comorbid BD.^8,9 Several studies suggest that comorbid personality disorders represent a negative prognostic factor in the course of mood disorders, and the presence of BPD in patients with BD seems to be associated with more severe clinical presentations, greater treatment complexity, a higher number of depressive episodes, poor inter-episode functioning, and higher rates of other comorbidities, such as substance use disorders (SUDs).^8-11 The effect of BD on the course of BPD is unclear and fairly unexplored, although it has been suggested that better control of mood symptoms may lead to more stable psychosocial functioning in BPD.⁹

Whether BD and BPD are part of the same spectrum is a matter for debate.^12-14 Multidimensional approaches have been proposed to better characterize these disorders in at-risk populations, based on structured interviews, self-administered and clinician-rated clinical scales (Table 1), neuroimaging studies, biological markers, and machine-learning models.^15,16 Compelling evidence suggests that BD and BPD have distinct underlying neurobiological and psychopathological mechanisms^12,13; however, the differential diagnosis still relies on phenotypical features, since the search for biological markers has not yet identified specific biomarkers that can be used in clinical practice.

Continue to: Core features of BPD...

Core features of BPD, such as mood lability, impulsivity, and risk-taking behaviors, are also part of the diagnostic criteria for BD (Table 2).¹ Similarly, depressive symptoms prevail in the course of BD.^17,18 This adds complexity to the differential because “depressivity” is also part of the diagnostic criteria for BPD.¹ Therefore, comprehensive psychiatric assessments and longitudinal observations are critical to diagnostic accuracy and treatment planning. Further characterization of symptoms, such as onset patterns, clinical course, phenomenology of symptoms (eg, timing, frequency, duration, triggers), and personality traits, will provide information to properly distinguish these 2 syndromes when, for example, it is unclear if the “mood swings” and impulsivity are part of a mood or a personality disorder (Table 3).

Clinical features: A closer look

Borderline personality disorder. Affect dysregulation, emotional instability, impoverished and unstable self-image, and chronic feelings of emptiness are core features of BPD.^1,5,19 These characteristics, when combined with a fear of abandonment or rejection, a compromised ability to recognize the feelings and needs of others, and extremes of idealization-devaluation, tend to culminate in problematic and chaotic relationships.^6,19 Individuals with BPD may become suspicious or paranoid under stressful situations. Under these circumstances, individuals with BPD may also experience depersonalization and other dissociative symptoms.^6,20 The mood lability and emotional instability observed in patients with BPD usually are in response to environmental factors, and although generally intense and out of proportion, they tend to be ephemeral and short-lived, typically lasting a few hours.^1,5 The anxiety and depressive symptoms reported by patients with BPD frequently are associated with feelings of “falling apart” or “losing control,” pessimism, shame, and low self-esteem. Coping strategies tend to be poorly developed and/or maladaptive, and individuals with BPD usually display a hostile and antagonistic demeanor and engage in suicidal or non­suicidal self-injury (NSSI) behaviors as means to alleviate overwhelming emotional distress. Impulsivity, disinhibition, poor tolerance to frustration, and risk-taking behaviors are also characteristic of BPD.^1,5 As a result, BPD is usually associated with significant impairment in functioning, multiple hospitalizations, and high rates of comorbid mood disorders, posttraumatic stress disorder (PTSD), SUDs, and death by suicide.

Bipolar disorder. Conversely, the fluctuations in mood and affect observed in patients with BD are usually episodic rather than pervasive, and tend to last longer (typically days to weeks) compared with the transient mood shifts observed in patients with BPD.^4,17,18 The impulsivity, psychomotor agitation, and increased goal-directed activity reported by patients with BD are usually seen in the context of an acute affective episode, and are far less common during periods of stability or euthymic affect.^4,17,18 Grandiosity and inflated self-esteem—hallmarks of a manic or hypomanic state—seem to oppose the unstable self-image observed in BPD, although indecisiveness and low self-worth may be observed in individuals with BD during depressive episodes. Antidepressant-induced mania or hypomania, atypical depressive episodes, and disruptions in sleep and circadian rhythms may be predictors of BD.^4,21 Furthermore, although psychosocial stressors may be associated with acute affective episodes in early stages of bipolar illness, over time minimal stressors are necessary to ignite new affective episodes.^22,23 Although BD is associated with high rates of suicide, suicide attempts are usually seen in the context of an acute depressive episode, and NSSI behaviors are less common among patients with BD.²⁴

Lastly, other biographical data, such as a history of early life trauma, comorbidity, and a family history of psychiatric illnesses, can be particularly helpful in establishing the differential diagnosis between BD and BPD.²⁵ For instance, evidence suggests that the heritability of BD may be as high as 70%, which usually translates into an extensive family history of bipolar and related disorders.²⁶ In addition, studies suggest a high co-occurrence of anxiety disorders, attention-deficit/hyperactivity disorder, and SUDs in patients with BD, whereas PTSD, SUDs, and eating disorders tend to be highly comorbid with BPD.²⁷ Childhood adversity (ie, a history of physical, sexual, or emotional abuse, or neglect) seems to be pivotal in the genesis of BPD and may predispose these individuals to psychotic and dissociative symptoms, particularly those with a history of sexual abuse, while playing a more secondary role in BD.^28-31

Implications of misdiagnosis

In the view of the limitations of the existing models, multidimensional approaches are necessary to improve diagnostic accuracy. Presently, the differential diagnosis of BD and BPD continues to rely on clinical findings and syndromic classifications. Misdiagnosing BD and BPD has adverse therapeutic and prognostic implications.³² For instance, while psychotropic medications and neuromodulatory therapies (eg, electroconvulsive therapy, repetitive transcranial magnetic stimulation) are considered first-line treatments for patients with BD, psychosocial interventions tend to be adjunctive treatments in BD.³³ Conversely, although pharmacotherapy might be helpful for patients with BPD, psychosocial and behavioral interventions are the mainstay treatment for this disorder, with the strongest evidence supporting cognitive-behavioral therapy, dialectical behavioral therapy, mentalization-based therapy, and transference-focused therapy.^34-36 Thus, misdiagnosing BD as BPD with comorbid depression may result in the use of antidepressants, which can be detrimental in BD. Antidepressant treatment of BD, particularly as monotherapy, has been associated with manic or hypomanic switch, mixed states, and frequent cycling.²¹ Moreover, delays in diagnosis and proper treatment of BD may result in protracted mood symptoms, prolonged affective episodes, higher rates of disability, functional impairment, and overall worse clinical outcomes.²⁴ In addition, because behavioral and psychosocial interventions are usually adjunctive therapies rather than first-line interventions for patients with BD, misdiagnosing BPD as BD may ultimately prevent these individuals from receiving proper treatment, likely resulting in more severe functional impairment, multiple hospitalizations, self-inflicted injuries, and suicide attempts, since psychotropic medications are not particularly effective for improving self-efficacy and coping strategies, nor for correcting cognitive distortions, particularly in self-image, and pathological personality traits, all of which are critical aspects of BPD treatment.

Continue to: Several factors might...

Several factors might make clinicians reluctant to diagnose BPD, or bias them to diagnose BD more frequently. These include a lack of familiarity with the diagnostic criteria for BPD, the phenotypical resemblance between BP and BPD, or even concerns about the stigma and negative implications that are associated with a BPD diagnosis.^32,37,38

Whereas BD is currently perceived as a condition with a strong biological basis, there are considerable misconceptions regarding BPD and its nature.^4-6,22,26 As a consequence, individuals with BPD tend to be perceived as “difficult-to-treat,” “uncooperative,” or “attention-seeking.” These misconceptions may result in poor clinician-patient relationships, unmet clinical and psychiatric needs, and frustration for both clinicians and patients.³⁷

Through advances in biological psychiatry, precision medicine may someday be a part of psychiatric practice. Biological “signatures” may eventually help clinicians in diagnosing and treating psychiatric disorders. Presently, however, rigorous history-taking and comprehensive clinical assessments are still the most powerful tools a clinician can use to accomplish these goals. Finally, destigmatizing psychiatric disorders and educating patients and clinicians are also critical to improving clinical outcomes and promoting mental health in a compassionate and empathetic fashion.

Bottom Line

Despite the phenotypical resemblance between bipolar disorder (BP) and borderline personality disorder (BPD), the 2 are independent conditions with distinct neurobiological and psychopathological underpinnings. Clinicians can use a rigorous assessment of pathological personality traits and characterization of symptoms, such as onset patterns, clinical course, and phenomenology, to properly distinguish between BP and BPD.

Related Resources

• Fiedorowicz JG, Black DW. Borderline, bipolar, or both? Frame your diagnosis on the patient history. Current Psychiatry. 2010; 9(1):21-24,29-32.
• Zimmerman M. Improving the recognition of borderline personality disorder. Current Psychiatry. 2017;16(10):13-19.
• National Institute of Mental Health. Overview on bipolar disorder. www.nimh.nih.gov/health/publications/bipolar-disorder/index.shtml. Revised October 2018.
• National Institute of Mental Health. Overview on borderline personality disorder. www.nimh.nih.gov/health/publications/borderline-personality-disorder-fact-sheet/index.shtml.

Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.

Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.

“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”

Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.

One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.

Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”

Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.

SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.

Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.

Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.

“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”

Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.

One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.

Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”

Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.

SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.

Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.

Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.

“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”

Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.

One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.

Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”

Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.

SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

SAN DIEGO – You don’t have to stop prescribing lithium when patients go on ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure treatment.

Some might opt to do that, but there’s no need to worry. In fact, the reason both classes are known to protect the kidneys is that they were tested with lithium; it was used to measure the drug’s effects on renal clearance, according to Stephen R. Saklad, PharmD, director of psychiatric pharmacy and clinical professor at the University of Texas at Austin.

There is interaction, but “lithium is not toxic in the presence of an ACE or an RB. You just have to adjust the dose,” he said at the annual Psych Congress.

Dr. Saklad shared lithium drug interaction pearls during a video interview at the meeting, including also using lithium with diuretics and NSAIDs. “The worst offender is probably my favorite of the NSAIDs, which is ibuprofen,” he said.

Most of the time with lithium, all that’s needed is a dose adjustment up or down of either it or the coadministered medication.

The overall guiding principle, he said, is that “lithium follows sodium. Anything that alters sodium in the body is going to alter sodium.”

[email protected]

SAN DIEGO – You don’t have to stop prescribing lithium when patients go on ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure treatment.

Some might opt to do that, but there’s no need to worry. In fact, the reason both classes are known to protect the kidneys is that they were tested with lithium; it was used to measure the drug’s effects on renal clearance, according to Stephen R. Saklad, PharmD, director of psychiatric pharmacy and clinical professor at the University of Texas at Austin.

There is interaction, but “lithium is not toxic in the presence of an ACE or an RB. You just have to adjust the dose,” he said at the annual Psych Congress.

Dr. Saklad shared lithium drug interaction pearls during a video interview at the meeting, including also using lithium with diuretics and NSAIDs. “The worst offender is probably my favorite of the NSAIDs, which is ibuprofen,” he said.

Most of the time with lithium, all that’s needed is a dose adjustment up or down of either it or the coadministered medication.

The overall guiding principle, he said, is that “lithium follows sodium. Anything that alters sodium in the body is going to alter sodium.”

[email protected]

SAN DIEGO – You don’t have to stop prescribing lithium when patients go on ACE inhibitors or angiotensin-receptor blockers (ARBs) for blood pressure treatment.

Some might opt to do that, but there’s no need to worry. In fact, the reason both classes are known to protect the kidneys is that they were tested with lithium; it was used to measure the drug’s effects on renal clearance, according to Stephen R. Saklad, PharmD, director of psychiatric pharmacy and clinical professor at the University of Texas at Austin.

There is interaction, but “lithium is not toxic in the presence of an ACE or an RB. You just have to adjust the dose,” he said at the annual Psych Congress.

Dr. Saklad shared lithium drug interaction pearls during a video interview at the meeting, including also using lithium with diuretics and NSAIDs. “The worst offender is probably my favorite of the NSAIDs, which is ibuprofen,” he said.

Most of the time with lithium, all that’s needed is a dose adjustment up or down of either it or the coadministered medication.

The overall guiding principle, he said, is that “lithium follows sodium. Anything that alters sodium in the body is going to alter sodium.”

[email protected]