Conditional probability of response or nonresponse of placebo compared with antidepressants or St John's Wort in major depressive disorder

In antidepressant randomized controlled trials of major depression, the placebo-response rate has gradually been increasing by about 7% per decade over the past 20 years. In recent years, various lines of investigation have focused on characterizing and differentiating response patterns to antidepressants and placebo, particularly with regard to the time course of response. Antidepressant-specific drug effects occur after the first 2 weeks of treatment and are stable, whereas placebo responses occur early and are variable. On the other hand, regardless of whether clinical improvement is attributable to drug or placebo, clinical response during the first 2 weeks of treatment has been shown to be highly predictive of eventual clinical response and vice versa. In this post hoc investigation, we first examined the time course of the placebo response pattern of subjectswho responded to placebo, compared with 2 conventional antidepressants and the natural antidepressant SJW. Our findings are in agreement with previous investigations, which collectively suggest that placebo response tends to occur in the early weeks of clinical trials. In our sample, 76% of eventual placebo responders displayed partial improvement by 2 weeks of treatment, and by 4 weeks of treatment, the bulk of early response was 92%. One of the major dilemmas for clinicians in psychiatric practice is ‘‘when to call a nonresponder, a nonresponder.’’ The results of our analysis may potentially influence clinicians to be more proactive when they do not see encouraging results early in the course of antidepressant treatment, and to undertake more aggressive measures such as faster dose increases and/or augmentation therapy. Thereby, if response is to occur, partial response will often occur in the first 2 weeks. Our findings also suggest that the placebo pattern of response occurs in subjects who participate in natural remedy studies similar to that of those studies that focus exclusively on synthetic antidepressants.