Antidepressant Discontinuation in Bipolar Depression

Apr 23, 2010The Journal of clinical psychiatry

Long-term safety and effectiveness of stopping antidepressants in bipolar depression: results from a controlled clinical trial

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Abstract

Antidepressant continuation may lead to a trend of less severe depressive symptoms with a mean difference of -1.84 in DSM-IV depression criteria.

Patients who continued antidepressants showed a mild delay in depressive episode relapse, with a hazard ratio of 2.13.
No significant increase in manic symptoms was observed among those who continued antidepressants, with a mean difference of +0.23 in DSM-IV mania criteria.
There were no significant differences in the prevalence or severity of new depressive or manic episodes between the two groups.
Patients with rapid-cycling bipolar disorder had three times more depressive episodes when continuing antidepressants compared to non-rapid cycling patients (1.29 vs 0.42 episodes/year).
Overall, this study did not find significant long-term benefits of antidepressants in treating bipolar disorder.

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OBJECTIVE: To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression.

METHOD: In the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups.

RESULTS: The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria = -1.84 [95% CI, -0.08 to 3.77]) and mildly delayed depressive episode relapse (HR = 2.13 [1.00-4.56]), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 [-0.73 to 1.20]). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P = .04).

CONCLUSIONS: This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened outcomes with modern antidepressant continuation.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00012558.

Antidepressant Discontinuation in Bipolar Depression

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