BACKGROUND: Approximately 3% of the population suffer from chronic depression. These persons have significant impairments in psychosocial function and work performance, use health care resources disproportionately, and have more suicide attempts and hospitalizations than patients with acute depression. Because chronic depression often responds poorly to monotherapy, the authors compared nefazadone with and without cognitive behavioral-analysis psychotherapy in this group.
POPULATION STUDIED: The investigators screened 1035 patients and enrolled 681. Patients were excluded for a large number of comorbid conditions. Patients who had failed to respond to an adequate trial of nefazadone or the cognitive behavioral-analysis system of psychotherapy were also excluded. The remaining 681 patients came from 12 academic centers between 1996 and 1997. They were aged between 18 and 75 years and scored at least 20 on the Hamilton Rating Scale for Depression. Approximately one third had a history of anxiety disorder, and more than half had a diagnosis of coexisting personality disorder.
STUDY DESIGN AND VALIDITY: Patients were randomly assigned to receive nefazadone, psychotherapy, or a combination of both. Although patients and clinicians were not blinded to their treatment group, the clinical raters who evaluated the Hamilton Rating Scale for Depression were masked regarding the treatment assignment. The investigators performed a modified intention-to-treat analysis that included all patients who attended at least one treatment session and had at least one assessment after the baseline evaluation. The groups were similar in terms of diagnosis, duration of symptoms, past antidepressant use, previous psychotherapy, and global assessment of function score.
OUTCOMES MEASURED: The primary outcome was the overall rate of response at 12 weeks, which was the sum of patients with a satisfactory response and remission using the Hamilton Depression Score Rating Scale. A satisfactory response was defined as a reduction of 50% on the rating scale from baseline to weeks 10 and 12, while remission was defined as a score of 8 or less at weeks 10 and 12.
RESULTS: For the modified intention-to-treat analysis, the overall rates of response were 48% in the psychotherapy group (95% confidence interval [CI], 41.5%-54.8%), 48% (95% CI, 41%-54.3%) in the nefazadone group, and 73% (95% CI, 68.6%-80.1%) in the combined treatment group (P <.001 for the difference between each monotherapy and combined therapy). The rates of remission were 33% in the psychotherapy group, 29% in the nefazadone group, and 48% in the combined treatment group (P <.001). The rates of discontinuation were similar in the 3 groups, with 24% not completing the trial. Patients receiving nefazadone were more likely to withdraw because of adverse drug effects (including headache, dry mouth, somnolence, dizziness, agitation, and gastrointestinal symptoms), while those in psychotherapy tended to withdraw because of time constraints or because they wanted medication instead of psychotherapy.
Patients with chronic depression benefit more from a combination of medical treatment with nefazadone and cognitive behavioral-analysis psychotherapy than from either intervention alone (number needed to treat=4). For every 4 patients treated with combined therapy instead of monotherapy, 1 additional patient will have a satisfactory response or remission at 12 weeks. It is unclear how long the effect lasts or how long such therapy would be needed. It is likely that other antidepressants will give similar results to nefazadone.