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 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.

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 strategies. This study examined the tolerability of a weekly dose and its equivalence to daily dosing of FLX for the continuation phase of treatment for major depressive disorder (MDD). One hundred fourteen subjects initially received open-label treatment with 20 mg of FLX daily for 7 weeks. Subsequently, 70 subjects with a score on the Hamilton Rating Scale for Depression (HAM-D) of 12 or less were randomly assigned in a double-blind design to one of three treatment groups: 20 mg FLX daily (N = 21), 60 mg FLX weekly (N = 28), or placebo (N = 21) and were followed for 7 weeks. HAM-D scores and blood 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 NFLX differed across the treatment groups, yet no statistically significant difference in HAM-D scores was observed. There was no difference in the dropout rate across the groups. Subjects could not correctly identify the treatment group into which they were assigned. Weekly dosing of FLX seems to be well tolerated and possibly as effective as daily dosing in maintaining the therapeutic response in subjects with MDD.

Disagreement in the reporting of depressive symptoms between patients with dementia of the Alzheimer type and their collateral sources.

The authors investigated sources of disagreement on the Geriatric Depression Scale (GDS) between patients and their collateral sources (CSs). There were 198 subjects with possible or probable Alzheimer's disease (DAT) and 64 cognitively intact subjects evaluated at an outpatient geriatric assessment center. The 30-item GDS was completed by the patient and the CS version of the GDS by the CS. A sizable discrepancy was found in the reporting of depressive symptoms by the subjects vs. the CSs. Multiple-regression analyses revealed that both level of insight and level of physical illness in the subjects with DAT significantly influenced the discrepancy. An increased sense of burden in the CSs was associated with a larger symptom gap in both DAT and control subjects. CSs consistently perceived more depressive symptoms than subjects, especially subjects with DAT who had no insight into their cognitive impairment.