The effects of psychotherapy, nefazodone, and their combination on subjective assessment of disturbed sleep in chronic depression.

STUDY OBJECTIVES: The purpose of the study was to compare the effects of psychotherapy, nefazodone, and their combination on subjective measures of sleep in patients with chronic forms of major depression. DESIGN: Participants were randomized to receive 12 weeks of treatment with one of the three interventions. SETTING: The study was conducted in parallel at 12 academic institutions and was approved by the Human Subjects Committee at each site. PARTICIPANTS: 484 adult outpatients (65.29% female) who met DSM-IV criteria for one of three chronic forms of major depression. INTERVENTIONS: Psychotherapy (16-20 sessions) was provided by certified therapists following a standardized treatment manual for Cognitive Behavioral Analysis System of Psychotherapy (CBASP), a variant of cognitive psychotherapy developed for chronic depression. Pharmacotherapy consisted of open-label nefazodone, 300-600 mg per day in two divided doses prescribed by psychiatrists. The clinical management visits were limited to 15-20 minutes and followed a standardized protocol. Combination treatment consisted of both therapies. MEASUREMENTS AND RESULTS: Depression outcome was determined by the 24-item Hamilton Rating Scale for Depression and the 30-item Inventory of Depressive Symptomatology-Self Rating. Sleep outcome was measured prospectively with daily sleep diaries that were completed a week prior to HRSD assessments at baseline and after 1, 2, 3, 4, 8, and 12 weeks of treatment. Although nefazodone alone and CBASP alone had comparable impact on global measures of depression outcome, only monotherapy with nefazodone improved early morning awakening and total sleep time. Significant improvements in sleep quality, time awake after sleep onset, latency to sleep onset, and sleep efficiency were present in each of the three treatment groups. These improvements, however, occurred earlier in the course of treatment for participants receiving nefazodone, alone or in combination with CBASP. CONCLUSIONS: Nefazodone therapy may have a direct impact on disturbed sleep associated with depression beyond what would be expected if the improvements were all a consequence of improved depression.