Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression

Biol Psychiatry. 2003 Oct 15;54(8):806-17. doi: 10.1016/s0006-3223(02)01971-6.

Abstract

Background: Maintenance treatment to prevent recurrences is recommended for chronic forms of major depressive disorder (MDD), but few studies have examined maintenance efficacy of antidepressants with chronic MDD. This randomized, placebo-controlled study of the efficacy and safety of nefazodone in preventing recurrence was conducted for patients with chronic MDD.

Methods: A total of 165 outpatients with chronic, nonpsychotic MDD, MDD plus dysthymic disorder ("double-depression"), or recurrent MDD with incomplete inter-episode recovery, who achieved and maintained a clinical response during acute and continuation treatment with either nefazodone alone or nefazodone combined with psychotherapy, were randomized to 52 weeks of double-blind nefazodone (maximum dose 600 mg/day) or placebo. The occurrence of major depressive episodes during maintenance treatment was assessed with the 24-item Hamilton Rating Scale for Depression, a DSM-IV MDD checklist, and a blinded review of symptom exacerbations by a consensus committee of research clinicians.

Results: Application of a competing-risk model that estimated the conditional probability of recurrence among those patients remaining on active therapy revealed a significant (p =.043) difference between nefazodone (n = 76) and placebo (n = 74) when the latter part of the 1-year maintenance period was emphasized. At the end of 1 year, the conditional probability of recurrence was 30.3% for nefazodone-treated patients, compared with 47.5% for placebo-treated patients. Prior concomitant psychotherapy during acute/continuation treatment, although enhancing the initial response, was not associated with lower recurrence rates. Discontinuations due to adverse events were relatively low for both nefazodone (5.3%) and placebo (4.8%). Somnolence was significantly greater among the patients taking active medication (15.4%), compared with placebo (4.6%).

Conclusions: Nefazodone is well-tolerated and is an effective maintenance therapy for chronic forms of MDD.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Chronic Disease
  • Combined Modality Therapy
  • Cross-Over Studies
  • Depressive Disorder, Major / prevention & control
  • Depressive Disorder, Major / therapy*
  • Double-Blind Method
  • Eligibility Determination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines
  • Psychotherapy / methods*
  • Recurrence
  • Substance Withdrawal Syndrome / epidemiology
  • Substance Withdrawal Syndrome / etiology
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*

Substances

  • Antidepressive Agents, Second-Generation
  • Piperazines
  • Triazoles
  • nefazodone