Suicide risk in placebo-controlled studies of major depression

Objective: The purpose of this study was to determine if fear of an increas ed risk of attempted suicide in placebo groups participating in placebo-con trolled studies is an argument against the performance of placebo-controlle d trials in studies of major depression. Method: All short-term and long-term, placebo-controlled, double-blind stud ies that were part of a registration dossier for the indication of major de pression that were submitted to the Medicines Evaluation Board, the regulat ory authority of the Netherlands, from 1983 to 1997 were reviewed for attem pted suicide. In addition, all long-term, placebo-controlled studies from a MEDLINE search that were conducted in the last decade in patients with maj or 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 plac ebo groups and active compound groups. The incidence of attempted suicide w as 0.4% in both placebo groups and active compound groups. in eight long-te rm studies with 1,949 patients, the incidence of suicide in the placebo gro ups was 0.0% and 0.2% in the active compound groups. Attempted suicide occu rred in 0.7% of both placebo groups and active compound groups. In seven lo ng-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 gro ups should not be an argument against performing short-term and long-term, placebo-controlled trials in major depression.