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Bipolar in Perinatal Setting

CE / CME

eCase: Treatment Considerations for Bipolar in a Perinatal Setting

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Social Workers: 1.00 ASWB ACE CE Credit

Pharmacists: 1.00 contact hour (0.1 CEUs)

Psychologists: 1.00 APA CE Credit

Nurses: 1.00 Nursing contact hour

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: December 22, 2022

Expiration: December 21, 2023

Joseph F. Goldberg
Joseph F. Goldberg, MD
CME/CE Information

Activity

Progress
1
Course Completed

Depressive features represent the predominant mood state in patients with bipolar I or II disorder (70% to 80%1) and pose numerous diagnostic and therapeutic challenges for healthcare professionals. In patients with bipolar I disorder, it has been estimated that the average length of a depressive episode is 13 weeks.2 Patients with bipolar depression are often misdiagnosed as having unipolar major depressive disorder (MDD) and may incur delays of 5-10 years from initial symptom onset to appropriate treatment. Complications from delayed treatment initiation may lead to the occurrence of more frequent episodes via “kindling” or behavioral sensitization (ie, more episodes beget more episodes with decreasing levels of external stressors as precipitants),3 more extensive comorbid psychiatric conditions,4 less interepisode recovery,4 and a heightened risk for suicidal behavior.5 The differential diagnosis of bipolar depression vs MDD hinges on recognizing the presence of a prior/lifetime manic or hypomanic episode. Additional features that may corroborate a diagnosis of bipolar vs unipolar MDD include those associated with bipolar disorder, such as an earlier age at onset, a family history of bipolar disorder, atypical depressive symptoms, poorer response to antidepressants, psychosis during mood episodes, highly recurrent mood episodes, and comorbid substance use disorders.6

Although psychosis and hypomania cannot coexist, either can occur in the depressed phase of illness.2 Phenomenologically, episodes of bipolar depression in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder program were shown more often than not to involve concomitant subthreshold features of mixed manic/hypomanic symptoms (31.2% had no manic symptoms vs 54.0% with subthreshold mixed/hypomanic symptoms, and an additional 14.8% with full mixed episodes).7 Presence of mixed symptoms may contribute to a heightened risk for mood destabilization with traditional monoaminergic antidepressants. Pharmacotherapy with traditional monoaminergic antidepressants has not been shown to be more efficacious than the use of placebos or mood stabilizers alone and carry a small but significant increased risk for causing destabilization of mood during long-term exposure.8,9 Studies of monoaminergic antidepressant use in bipolar depression suggest that they may be appropriate and efficacious for a relatively small minority of individuals, of note, those with bipolar II rather than bipolar I disorder,10 those with no mixed features,7,11 no recent mania/hypomania,12 those with a robust and unequivocal initial antidepressant response,13 no history of alcohol or substance use comorbidity,14 and no personal history of previous antidepressant-associated mania/hypomania.15 Hence, there is a compelling need for the development and expansion of novel pharmacotherapies that possess antidepressant properties without risk for destabilizing mood in bipolar depression.

Suicide risk is considerably elevated in people with bipolar disorder. Suicide attempts or completions typically occur during the depressed or mixed episode phases vs manic phases.16 In a review of 61 studies of completed suicide, Plans and colleagues17 found a 20- to 30-fold increased risk for suicide completions among patients with bipolar disorder compared with the general population. Although some studies report a higher risk for completed suicide in bipolar II than I disorder,17 other authors report no differences in rates of attempted suicide between bipolar I and II disorder.18 Regarding gender, suicide completion risk is higher in men with bipolar than women with bipolar.19

Among special populations of individuals with bipolar depression who may be at even greater risk for more extensive complications are women during their reproductive years, particularly in the setting of pregnancy and the postpartum. In fact, among women who are pregnant, suicide attempt and completion risk is higher in those with bipolar vs those with unipolar MDD.20 Furthermore, pregnancy represents a time of increased risk for mood episodes in women with bipolar disorder. In women with known bipolar-spectrum disorder, slightly more than one half may expect to incur a mood episode during pregnancy or the postpartum period, although as many as 1 in 5 pregnant patients with bipolar disorder may have previously gone undiagnosed.21 Risk factors for affective relapse during pregnancy in women with bipolar disorder include younger age at onset and a shorter duration of illness.22 Aside from mood complications, bipolar disorder also represents a risk for placental abnormalities and antepartal hemorrhages, as well as toxicities related to alcohol and illicit substance use, as compared with healthy subjects.23

With no prospective randomized controlled pharmacotherapy trials of bipolar depression in perinatal women, healthcare professionals must draw inferences about drug safety and efficacy from case registry data and observations from postmarketing pharmacovigilance reports. Pharmacotherapy for bipolar depression during pregnancy is complex. Lamotrigine confers protection against depressive episodes and has no established risk for teratogenicity or obstetrical complications24 but provides little protection against mania. Lithium remains a core treatment in all phases of bipolar disorder, although meta-analyses suggest its efficacy for acute bipolar depression may be relatively modest25 and eclipsed by its more predominant antimanic properties.26 Although its use during pregnancy, particularly during the first trimester, has been the subject of ongoing debate regarding relative risk for congenital cardiac malformations, that risk appears to be substantially lower than early estimates suggested,27 and prevailing views favor a risk–benefit analysis for lithium in pregnant women with bipolar disorder for whom benefits may be substantial and predominate over low teratogenic risk.28

Among second-generation antipsychotics, only several agents have known antidepressant properties. However, these agents—with the exceptions of quetiapine and olanzapine—have no relapse prevention data for depressive episodes in bipolar disorder and only minimal postmarketing pharmacovigilance data on pregnancy outcomes or long-term safety data postpartum. The challenges of accurately diagnosing and treating bipolar depression during pregnancy are therefore especially complex.