A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial.

BACKGROUND

Previous small trials have suggested that nefazodone does not suppress rapid-eye-movement (REM) sleep or increase REM latency in depressed patients, in contrast to fluoxetine. The effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures were directly compared in this 8-week, multicenter, double-blind, randomized, parallel-group study.

METHOD

Forty-four outpatients with moderate to severe, nonpsychotic major depressive disorder (DSM-III-R) and insomnia were randomly assigned to receive nefazodone (Days 1-7, 200 mg/day; Days 8-56, 400 mg/day) or fluoxetine (Days 1-56, 20 mg/day). Sleep measures were obtained at baseline, while patients were unmedicated, and at Weeks 2, 4, and 8 of treatment.

RESULTS

In 43 evaluable patients (23 nefazodone, 20 fluoxetine), nefazodone and fluoxetine demonstrated similar antidepressant efficacy. All significant values were p < .05. Fluoxetine significantly decreased sleep efficiency and REM sleep and increased number of awakenings, Stage 1 sleep, and REM latency compared with baseline. In contrast, nefazodone significantly decreased percentage of awake and movement time and did not alter sleep efficiency or number of awakenings, Stage 1 or REM sleep, or REM latency compared with baseline. Nefazodone was associated with significantly less change from baseline for sleep efficiency, number of awakenings, percentage of awake and movement time, percentage of REM and Stage 1 sleep, and REM latency compared with fluoxetine. Both fluoxetine- and nefazodone-treated patients also showed significant improvement in some clinician- and patient-rated sleep disturbance scores, but nefazodone-treated patients improved to a significantly greater extent than fluoxetine-treated patients in most measures.

CONCLUSION

While nefazodone and fluoxetine showed equivalent antidepressant efficacy, more objective, subjective, and clinician-rated measures of sleep disturbance were improved during treatment with nefazodone than with fluoxetine. These results suggest that antidepressant effects of medications can occur independently of drug-induced changes in objective, subjective, and clinician-rated measures of sleep. Further studies, including parallel placebo-controlled comparisons with nefazodone, are needed to further test this hypothesis.