Side effects and time course of response in a placebo-controlled trial of fluoxetine for the treatment of geriatric depression.

A high rate of improvement among patients who receive placebo in controlled trials of antidepressants can complicate the evaluation of true drug effect. Placebo response may be a reaction to the psychosocial factors of study participation or a function of changes in the natural course of depression. Drug side effects may also influence patients' expectations, and they should be distinguished from the somatic symptoms associated with major depression. The authors reanalyzed data from a large, multicenter, placebo-controlled clinical trial of fluoxetine treatment of geriatric depression to evaluate similarities and differences between responders and nonresponders in both treatment groups. Specifically, the authors examined weekly somatic complaints as possible predictors of response and of dropout, as well as the time course and onset of response. Fluoxetine was superior to placebo on all outcome measures. Among somatic complaints associated with fluoxetine response, headache before and after randomization was associated with a good response and anxiety after randomization was associated with a poor response. Somnolence before and after randomization was associated with a good placebo response. Early and persistent improvement occurred among similar proportions of responders in both groups. The difference between fluoxetine and placebo seemed to be a persistent response beginning during the 4th week. Pretreatment somnolence was associated with early, persistent improvement in both groups and may serve as a marker for placebo response.