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 effec t, 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 shou ld be distinguished fi om the somatic symptoms associated with major depres sion. The authors reanalyzed data from a large, multicenter, placebo-contro lled clinical trial of fluoxetine treatment of geriatric depression to eval uate similarities and differences between responders and nonresponders in b oth treatment groups. Specifically, the authors examined weekly somatic com plaints as possible predictors of response and of dropout, as well as the t ime course and onset of response. Fluoxetine was superior to placebo on all outcome measures. Among somatic complaints associated with fluoxetine resp onse, headache before and after randomization was associated with a good re sponse and anxiety after randomization was associated with a poor response. Somnolence before and after randomization was associated with a good place bo response. Early and persistent improvement occurred among similar propor tions of responders in both groups. The difference between fluoxetine and p lacebo seemed to be a persistent response beginning during the 4th week, Pr etreatment somnolence was associated with early, persistent improvement in both groups and may serve as a marker for placebo response.