Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder

Abstract

Antidepressant medications are typically taken on a daily basis owing to both tradition and the pharmacokinetics of these agents. Because fluoxetine and its primary metabolite norfluoxetine have long half-lives and flat dose-response curves, we examined the tolerability of a weekly dose and its equivalence to daily dosing during the continuation phase of treatment for major depressive disorder (MDD). Open-label treatment with 20 mg of fluoxetine daily for 7 weeks began with 114 subjects. Subsequently, 70 subjects who met criteria for response were randomly assigned in a double-blind design to 1 of 3 treatment groups (20 mg of fluoxetine daily [N = 21], 60 mg of fluoxetine weekly [N = 28], or placebo [N = 21]) and followed for 7 weeks. No statistically significant differences were observed in several clinical measures. Tolerability in the 3 groups was similar; there was no difference in dropout rates or adverse events. Hence, weekly dosing of fluoxetine appears to be well tolerated and possibly as effective as daily dosing in the treatment of MDD. It is proposed that less frequent dosing could potentially benefit patients by enhancing adherence and minimizing the risk of side effects and drug-drug interactions.