Exploring Treatment Alternatives: Weekly Dosing of Fluoxetine for the Continuation Phase of Major Depressive Disorder

Antidepressant medications are typically taken on a daily basis owing to both tradition and thepharmacokinetics of these agents. Because fluoxetine and its primary metabolite norfluoxetine havelong half-lives and flat dose-response curves, we examined the tolerability of a weekly dose and itsequivalence 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-blinddesign 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 wereobserved in several clinical measures. Tolerability in the 3 groups was similar; there was no differencein dropout rates or adverse events. Hence, weekly dosing of fluoxetine appears to be well toleratedand possibly as effective as daily dosing in the treatment of MDD. It is proposed that less frequentdosing could potentially benefit patients by enhancing adherence and minimizing the risk of side effectsand drug-drug interactions.