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To the Editor: Dr Walsh and colleagues¹ reported that response to placebo antidepressants in published clinical trials has improved over the past 20 years. The authors attributed this improvement to changes in the type of patients who participate in clinical trials. That is, because a larger proportion of the population has been receiving treatment for depression in recent years, clinical trials probably draw more individuals with milder, briefer, and more responsive forms of depression.

Our historical analysis of placebo responses in clinical trials of pharmacotherapies for nicotine dependence reinforces the hypothesis that shifting responses to placebo may reflect subtle historical changes in patient populations.² In contrast to the findings with placebo antidepressants, we found that the published effectiveness of placebo tobacco therapies (nicotine replacement therapies as well as bupropion, clonidine, and naltrexone) had declined between 1983 and 1999. For example, over the period there were significant declines in abstinence rates . . . [Full Text of this Article]

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