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Predictors of Relapse During Fluoxetine Continuation or Maintenance Treatment of Major Depression

J Clin Psychiatry 2000;61:518-524

Background: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy.

Method: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse.

Results: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained.

Conclusion: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.