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Short-term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression – low manic switch rate


Jay D Amsterdam MD, Depression Research Unit, University Science Center, 3rd Floor, 3535 Market Street, Philadelphia, PA 19104, USA. Fax: (215) 662-6443;


Objectives:  Current guidelines for the initial treatment of bipolar type II (BP II) major depressive episode (MDE) recommend using either a mood stabilizer alone or a combination of a mood stabilizer plus a selective serotonin re-uptake inhibitor (SSRI). This recommendation is the result of concern over antidepressant-induced manic switch episodes. However, recent evidence suggests that the manic switch rate may be low in BP II MDE during SSRI therapy.

Methods:  As part of a randomized, double-blind, placebo-controlled relapse-prevention study of fluoxetine monotherapy in BP II MDE, 37 patients received open-label fluoxetine 20 mg every day for up to 8 weeks. Outcome measures included the Hamilton Depression Rating (HAM-D 17) rating and the Young Mania Rating (YMR) scale.

Results:  Eleven of 23 patients (48%) who completed 8 weeks of fluoxetine treatment showed a HAM-D 17 reduction of ≥50%, while 14 (38%) of all treated patients had ≥50% reduction in baseline HAM-D 17 score. Using a conservative YMR score of ≥8 to identify hypomanic symptoms, the frequency of patients with YMR score ≥8 during fluoxetine did not differ from that seen during the screen and baseline period. Only three patients (7.3%) had symptoms suggestive of hypomania, and only one patient stopped treatment because of a rapid mood swing into depression.

Limitations:  Fluoxetine was given at a fixed dose of 20 mg everyday. Fluoxetine was prescribed in an open-label manner, and the sample size was limited.

Conclusions:  These observations support the findings of a low manic switch rate during SSRI monotherapy of BP II MDE, and suggest that fluoxetine monotherapy may be a safe and effective initial treatment of BP II MDE.