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 me chanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepr essants as a group prior to unblinding the specific individual drug efficac y and tolerability data in this ongoing clinical trial. Methods: Subjects included 64 bipolar patients who participated at five sit es in a 10-week double-blind trial for depression and a 1-year blinded cont inuation 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 buprop ion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Dai ly ratings on the National Institute of Mental Health-Life Chart Methodolog y (NIMH-LCM) were inspected for the degree of improvement on the Clinical G lobal Impressions scale as revised for bipolar illness (CGI-BP) and the occ urrence 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. Thir teen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six int o 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. 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. Thir teen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six int o 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 sec ond-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 wi ll be assessed in the next phase of the study after more subjects are recru ited and the blind is broken.