Atypical antipsychotics in bipolar depression: a new major option?

Abstract

In addition to antidepressants, lithium and anticonvulsants, also atypical antipsychotics have been studied in the treatment of acute bipolar depression. Olanzapine (5-20 mg/d) was effective compared to placebo, but in the same study less effective than the combination of olanzapine (6-12 mg/d) with fluoxetine (25-50 mg/d). After this finding further studies have used only the combination. Quetiapine has been studied more extensively. In two studies (Bolder I en Bolder II) quetiapine (300 and 600 mg/d) was more effective than placebo, with efficacy in patients with bipolar I as well as bipolar II depression, and with an effect size of quetiapine greater than olanzapine, and comparable with the olanzapine-fluoxetine combination. There was however no direct comparison. In two other placebo-controlled studies quetiapine (300 and 600 mg/d) was compared with lithium (600-1800 mg/d and plasma level 0.6-1.2 mEq/l, Embolden I) and with paroxetine (20 mg/d, Embolden II). In these studies the efficacy of quetiapine was confirmed, while neither lithium nor paroxetine were superior to placebo. In a follow-up of these two studies responders to quetiapine were randomised to continuation of quetiapine or switch to placebo, revealing more depressive recurrences with placebo than with continuation of quetiapine. Finally two studies evaluated the efficacy of aripiprazole and did not found evidence for efficacy.

 The studies suggest that quetiapine is now a major option in the treatment of bipolar depression, while there is also some evidence for efficacy of olanzapine. The antidepressant effect of atypical antipsychotics does not appear a class effect.