Weekly dosing of fluoxetine for the continuation phase of treatment of major depression: Results of a placebo-controlled, randomized clinical trial

Fluoxetine (FLX) has a unique pharmacokinetic profile, Its major metabolite , norfluoxetine (NFLX), possesses FLX's antidepressant efficacy and a half- life of 7 to 15 days, suggesting the possibility of nonstandard dosing stra tegies. This study examined the tolerability of a weekly dose and its equiv alence to daily dosing of FLX for the continuation phase of treatment for m ajor depressive disorder (MDD). One hundred fourteen subjects initially rec eived open-label treatment with 20 mg of FLX daily for 7 weeks. Subsequentl y, 70 subjects with a score on the Hamilton Rating Scale for Depression (HA M-D) of 12 or less were randomly assigned in a double-blind design to one o f three treatment groups: 20 mg FLX daily (N = 21), 60 mg FLX weekly (N = 2 8), or placebo (N = 21) and were followed for 7 weeks. HAM-D scores and blo od levels of FLX and NFLX were analyzed using a repeated-measures analysis of variance. During the double-blind phase, blood levels for both FLX and N FLX differed across the treatment groups, yet no statistically significant difference in HAM-D scores was observed. There was no difference in the dro pout rate across the groups. Subjects could not correctly identify the trea tment group into which they were assigned. Weekly dosing of FLX seems to be well tolerated and possibly as effective as daily dosing in maintaining th e therapeutic response in subjects with MDD.