BACKGROUND: If there is an increased risk of suicide in the placebo arms of placebo-controlled studies in patients with schizophrenia, it would be a strong ethical argument against the conduct of placebo-controlled studies in this patient population. We tested whether the risk of suicide and attempted suicide in the placebo arms of placebo-controlled studies among patients with schizophrenia is higher than in the active treatment arms of such studies. METHODS: All placebo-controlled double-blind studies that were part of a registration dossier for the indication schizophrenia, and that were submitted to the regulatory authority of the Netherlands from January 1, 1992, through December 31, 2002, were reviewed for suicide and attempted suicide. RESULTS: In 31 studies, 7152 patients were included: 1888 in placebo groups (398.2 person-years) and 5264 in active compound groups (981.3 person-years). One suicide occurred in the placebo groups (0.05%, or an incidence rate of 251 per 100,000 years of exposure) and 1 in the active compound groups (0.02%, or an incidence rate of 102 per 100,000 years of exposure). This difference was not statistically significant. Two attempted suicides occurred in the placebo groups (0.11%, or an incidence rate of 502 per 100,000 years of exposure) and 11 in the active compound groups (0.21%, or an incidence rate of 1121 per 100,000 years of exposure). This difference was also not statistically significant. CONCLUSION: Concern about increased risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials in schizophrenia, provided that appropriate precautions are taken.
RCT Entities:
BACKGROUND: If there is an increased risk of suicide in the placebo arms of placebo-controlled studies in patients with schizophrenia, it would be a strong ethical argument against the conduct of placebo-controlled studies in this patient population. We tested whether the risk of suicide and attempted suicide in the placebo arms of placebo-controlled studies among patients with schizophrenia is higher than in the active treatment arms of such studies. METHODS: All placebo-controlled double-blind studies that were part of a registration dossier for the indication schizophrenia, and that were submitted to the regulatory authority of the Netherlands from January 1, 1992, through December 31, 2002, were reviewed for suicide and attempted suicide. RESULTS: In 31 studies, 7152 patients were included: 1888 in placebo groups (398.2 person-years) and 5264 in active compound groups (981.3 person-years). One suicide occurred in the placebo groups (0.05%, or an incidence rate of 251 per 100,000 years of exposure) and 1 in the active compound groups (0.02%, or an incidence rate of 102 per 100,000 years of exposure). This difference was not statistically significant. Two attempted suicides occurred in the placebo groups (0.11%, or an incidence rate of 502 per 100,000 years of exposure) and 11 in the active compound groups (0.21%, or an incidence rate of 1121 per 100,000 years of exposure). This difference was also not statistically significant. CONCLUSION: Concern about increased risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials in schizophrenia, provided that appropriate precautions are taken.