Suicide risk in placebo-controlled studies of major depression.
OBJECTIVE
The purpose of this study was to determine if fear of an increased risk of attempted suicide in placebo groups participating in placebo-controlled studies is an argument against the performance of placebo-controlled trials in studies of major depression.


METHODS
All short-term and long-term, placebo-controlled, double-blind studies that were part of a registration dossier for the indication of major depression that were submitted to the Medicines Evaluation Board, the regulatory authority of the Netherlands, from 1983 to 1997 were reviewed for attempted suicide. In addition, all long-term, placebo-controlled studies from a MEDLINE search that were conducted in the last decade in patients with major depression were assessed for attempted suicide.


RESULTS
In 77 short-term studies with 12,246 patients in dossiers from the Medicines Evaluation Board, the incidence of suicide was 0.1% in both placebo groups and active compound groups. The incidence of attempted suicide was 0.4% in both placebo groups and active compound groups. In eight long-term studies with 1,949 patients, the incidence of suicide in the placebo groups was 0.0% and 0.2% in the active compound groups. Attempted suicide occurred in 0.7% of both placebo groups and active compound groups. In seven long-term MEDLINE studies, the incidence of attempted suicide in the placebo groups was not higher than in the groups treated with active compound.


CONCLUSIONS
Fear of increased risk of attempted suicide in the placebo groups should not be an argument against performing short-term and long-term, placebo-controlled trials in major depression.
Storosum
J G
JG
Medicines Evaluation Board of the Netherlands, Kalvermarkt 53, 2500 BE Den Haag, the Netherlands. jg.storosum@cbg-meb.nl
van Zwieten
B J
BJ
van den Brink
W
W
Gersons
B P
BP
Broekmans
A W
AW
D000928:Antidepressive Agents / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic / Q000592:standards / Q000706:statistics & numerical data*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D017277:Drug Approval / Q000379:methods; D006801:Humans; D015994:Incidence; D009426:Netherlands / Q000453:epidemiology; D010919:Placebos / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000517:prevention & control / Q000523:psychology / Q000706:statistics & numerical data; D000092864:Suicide Prevention
D000928:Antidepressive Agents; D010919:Placebos