Rate of switch in bipolar patients prospectively treated with second‐generation antidepressants as augmentation to mood stabilizers

Introduction: Bipolar patients with breakthrough major depressive episodes despite ongoing adequately‐dosed mood stabilizer medication were randomized in a double‐blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial. Methods: Subjects included 64 bipolar patients who participated at five sites in a 10‐week double‐blind trial for depression and a 1‐year blinded continuation maintenance phase for responders. Nonresponders were re‐randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health‐Life Chart Methodology (NIMH‐LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI‐BP) and the occurrence of hypomania or mania. Results: Thirty‐five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI‐BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty‐two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania. Conclusions: In this randomized double‐blind prospective study of three second‐generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.