Signal Detection and Placebo Response in Schizophrenia: Parallels with Depression

OBJECTIVE: Placebo response and the rate of failed clinical trials are increasing in schizophrenia, resembling previous experience with antidepressant clinical trials. In depression, the percent of patients randomized to placebo was shown to be strongly associated with drug-placebo differences (signal detection).We hypothesized that this factor would also be important in recent schizophrenia clinical trials. To test this hypothesis a database of acute schizophrenia placebo-controlled studies conducted between 1997 and 2008 was constructed. The database contained 27 studies, with 79 active treatment arms. As percentage of patients randomized to placebo increased, mean placebo improvement decreased (p = 0.047)…