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

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.