To the Editor The findings by Rutherford et al1 suggest that the average treatment change associated with placebo treatment in antipsychotic trials has increased since 1960, while the change associated with medication treatment decreased. In trying to explain these findings, their discussion focused on methodological matters, such as study design and population, but overlooked another likely confounding factor: the transition from first-generation antipsychotics to second-generation antipsychotics during the last 3 decades.