Some studies suggest that more severely ill patients with depression respond well to antidepressants and poorly to placebo, whereas those who are mildly ill respond equally well to antidepressants and placebo. This notion has implications for the design of clinical trials. To further assess and substantiate these putative predictors of antidepressant and placebo response, we assessed the Food and Drug Administration database of 45 phase II and III antidepressant clinical trials. The frequency of statistically significant differences between antidepressants and placebo was higher in the trials that included patients with more severe depression. In the antidepressant-treated groups, the magnitude of symptom reduction was significantly related to mean initial Hamilton Rating Scale for Depression (HAM-D) score; the higher the mean initial HAM-D score, the larger the change. With placebo treatment, however, the higher the mean initial HAM-D score, the smaller the change. Early discontinuation was more frequent among patients whose mean initial HAM-D scores were higher. These data may help inform the design of future antidepressant clinical trials.

No abstract

These findings fail to support either an overall difference in suicide risk between antidepressant- and placebo-treated depressed subjects in controlled trials or a difference between SSRIs and either other types of antidepressants or placebo.

Placebo response magnitude is suspected to affect the outcome of antidepressant clinical trials. To evaluate this, 52 randomized, double-blind, placebo-controlled clinical trials obtained from the FDA were examined to correlate placebo response magnitude with trial outcome. The magnitude of symptom reduction, percentage mean change from baseline in the Hamilton Depression Rating Scale (HAM-D), was assessed for patients assigned to placebo or an antidepressant. Correlation coefficients between symptom reduction with placebo and antidepressants and between symptom reduction with placebo and magnitude of advantage of antidepressants over placebo were assessed. A statistically significant positive correlation was seen between placebo and antidepressant response magnitude (r =.40, p <.001) and between placebo response magnitude and the advantage of antidepressants over placebo (r = -.592, p <.0001). Only 21.1% of antidepressant treatment arms in trials with high placebo response (>30% mean change from baseline) showed statistical superiority over placebo compared with 74.2% in trials with a low placebo response (< or =30). Response magnitude varies and has an important effect on antidepressant clinical trials, illustrating the need for a placebo arm to determine if the trial was sensitive to treatment differences and highlighting the dangers of cross-study comparisons.