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PubMed1998

Nefazodone and REM sleep: how do antidepressant drugs decrease REM sleep?

In previous uncontrolled studies, nefazodone, a new antidepressant drug, increased REM sleep or had no effect on REM sleep. We report a double-blind, placebo-controlled, parallel group study on effects of nefazodone (N) on polysomnographic sleep variables in healthy human volunteers. Nefazodone was administered for 16 consecutive days, and nocturnal sleep, as well as multiple sleep latency test (MSLT), was monitored before, during, and after N administration. We found that N had no effect on any measured REM sleep variable including REM sleep duration, REM density, and nocturnal REM sleep distribution. Nefazodone also had no significant effect on nocturnal total sleep time or NREM variables, but increased daytime alertness measured by the MSLT. Since N is a potent serotonin reuptake blocker, the present findings that N had no effect on REM sleep cast doubt on the hypothesis that antidepressant drugs decrease REM sleep by increasing serotonergic neurotransmission. A review of other relevant work also casts doubt on this hypothesis.

Adolescent↗

PubMed1994

A double-blind comparison of nefazodone, imipramine, and placebo in major depression.

BACKGROUND: Nefazodone is a 5-HT2-receptor antagonist and serotonin (5-HT) selective reuptake inhibitor. This study evaluates the safety and efficacy of nefazodone in patients with major depressive disorder (MDD) in comparison to imipramine and placebo treatments. It also compares two dose ranges of nefazodone to investigate its optimal dose range. METHOD: Nefazodone was evaluated in a 6-week, double-blind trial of novel design involving 180 patients meeting Research Diagnostic Criteria for major depressive disorder and having a minimum pretreatment score of 22 on the first 17 items of the Hamilton Rating Scale for Depression (HAM-D). Patients were randomly assigned to placebo (2-10 capsules/day), imipramine (50-250 mg/day), or nefazodone in two dose ranges (50-250 mg/day or 100-500 mg/day). RESULTS: Improvement on depression measures with nefazodone in the 100-500-mg/day dose range (endpoint mean = 460 mg/day) and imipramine (endpoint mean = 214 mg/day) exceeded that with placebo. Some benefit was also observed in the nefazodone 50-250-mg/day treatment group (endpoint mean = 242 mg/day), but it was suboptimal. Evidence of nefazodone's efficacy as an antidepressant was consistently observed on physician- (HAM-D, Clinical Global Impressions [CGI]) and patient-rated (CGI-patient rated) scales. By patient self-report, improvement of anxiety symptoms associated with depression was evident with nefazodone as early as the first week of treatment, and benefit was seen with both nefazodone dosage groups. Analyses of the physician's global assessments of therapeutic effect and side effects at end of treatment showed therapeutic benefit for both nefazodone and imipramine treatments; however, patients in the nefazodone treatment groups were significantly less troubled by adverse experiences than were imipramine-treated patients, resulting in a lower dropout rate for adverse experience. CONCLUSION: Nefazodone is a well-tolerated and effective antidepressant for the treatment of major depressive disorder.

Adult↗