Methodology of measuring the efficacy of antidepressants.

Evaluation of the efficacy of antidepressant agents needs to take into account factors which increase the "effect size", such as dosage, treatment duration, the use of two-phase trials, and pattern analysis of responders. Although many patients are thought to receive inadequate doses of antidepressants, relatively few dose-response studies have been performed. However, trials of both tricyclic antidepressants and phenelzine have shown that statistically significant improvements in outcome result from the use of higher dosages; the length of treatment may also affect results. In some studies, the proportion of patients showing a clear-cut response increased significantly among patients treated with active drug instead of placebo when the treatment period was extended from 4 to 6 weeks, independent of the dose used. There may thus be a distinct advantage in extending trials of antidepressants for a minimum of 6 weeks. Two-phase drug trials can be used to extend the trial period still further in responding patients, to emphasize the contrast between treatment and placebo effects and to eliminate type-2 errors. Twelve-week trials might increase the statistical power of the evaluation by 10-20%, in studies where the drug effect size is small. Pattern analysis of the timing and duration of patients' responses has been shown to aid the distinction of true responses from non-specific or placebo effects, and may be useful for evaluating data from studies of antidepressant agents which yield ambiguous results.