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Conclusions The markedly fluctuating placebo response patterns evidence an unstable 'signal' so leading principal studies to generate three mutually contradictory conclusions. We suggest that the increase in rates in the 1980s studies reflected the uptake and impact of 'major depression' being used as the diagnostic criterion, while the striking peaks and troughs observable over our study period argue for varying trial characteristics over time or rater biases in judging depression.Background Evidence provides inconsistent findings on ri