Further evidence that a placebo response to antidepressants can be identified

OBJECTIVE: The authors' goal was to analyze the acute phase of antidepressant drug treatment to identify placebo responses. METHOD: Patients rated as improved after 6 weeks of double-blind treatment with imipramine or phenelzine were followed for an additional 6 weeks of double-blind treatment. Initial responses were classified according to the speed of improvement (abrupt or gradual), the persistence or nonpersistence of improvement, and the timing of improvement (early or late onset). RESULTS: It was predicted that patients with nonpersistent, abrupt responses to the drugs were actually experiencing a placebo response and would have the worst prognosis. In fact, this group accounted for a disproportionate number of the relapses. Nonpersistent responders to a drug had a 23.7% relapse rate, but persistent responders had only a 9.0% relapse rate, a significant difference. CONCLUSIONS: The authors conclude that a significant proportion of relapses within the first 6 weeks of treatment with an active drug are not related to loss of a true drug effect. Rather, some are related to loss of nonspecific placebo effects, and abrupt nonpersistent responses during drug treatment are most likely the result of placebo effects.