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

Abstract

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.

• Authors: R M Post, L L Altshuler, M A Frye, T Suppes, A J Rush, P E Keck Jr, S L McElroy, K D Denicoff, G S Leverich, R Kupka, W A Nolen
• Journal: Bipolar disorders (Bipolar Disord) Vol. 3 Issue 5 Pg. 259-65 (Oct 2001) ISSN: 1398-5647 [Print] Denmark
• PMID: 11912569 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antidepressive Agents, Second-Generation

Topics

• Adult
• Aged
• Antidepressive Agents, Second-Generation (administration & dosage, therapeutic use)
• Bipolar Disorder (diagnosis, drug therapy)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Prospective Studies
• Severity of Illness Index