Placebo Response and Antidepressant Response

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Much of the response to an antidepressant is the result of placebo response. The placebo response embedded in drug response confounds studies seeking to identify brain mechanisms essential for pharmacologic response. Exclusion of patients who fail to meet entry criteria at the end of a placebo lead-in phase has been inadequate to reduce the effect of placebo during pharmacologic trials. This study focused on the placebo lead-in phase and examines whether change in severity of depression during placebo lead-in predicts change in depressive symptoms during antidepressant treatment. The subjects were patients aged 60-85 years with nonpsychotic unipolar major depression not attributed to dementing disorders, medical illnesses, or drugs causing depression and had a 24-item Hamilton Depression Rating Scale score of 18 or greater. After a two-week placebo lead-in, subjects with Hamilton Depression Rating Scale score of 18 or greater received 10 mg escitalopram for 12 weeks. Worsening or limited change in depression during placebo treatment predicted improvement in depressive symptoms during escitalopram treatment. Limited change in anxiety, melancholia, helplessness, and paranoia during placebo treatment were the strongest predictors of improvement in depression while on escitalopram. These findings, if replicated, may be used to characterize depressed older patients likely to respond to the pharmacologic action of antidepressants rather than the placebo response embedded in drug trials and thus improve the methodology of biomarker studies of antidepressant response. On a clinical level, depressed older patients who improve during a prolonged evaluation may be candidates for nonpharmacologic treatments because their drug response may be limited.