Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia.
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.


CONCLUSIONS
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.
Storosum
Jitschak G
JG
Medicines Evaluation Board of the Netherlands, Den Haag, the Netherlands. JG.Storosum@CBG-MEB.nl
van Zwieten
Barbara J
BJ
Wohlfarth
Tamar
T
de Haan
Lieuwe
L
Khan
Arif
A
van den Brink
Wim
W
D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002423:Cause of Death; D002985:Clinical Protocols / Q000592:standards; D018849:Controlled Clinical Trials as Topic / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D017277:Drug Approval / Q000379:methods; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D009026:Mortality; D009426:Netherlands; D018579:Patient Selection; D010919:Placebos / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000009:adverse effects; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000401:mortality*; D016037:Single-Blind Method; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000706:statistics & numerical data
D014150:Antipsychotic Agents; D010919:Placebos