Suicide Risk in Placebo-Controlled Trials of Treatment for Acute Manic Episode and Prevention of Manic-Depressive Episode

OBJECTIVE: The authors' goal was to investigate whether there is a greater suicide risk in the placebo arms of placebo-controlled studies of active medication for the treatment of acute manic episode and the prevention of manic depressive episode. If so, this would be a strong ethical argument against the conduct of such studies. METHOD: All placebo-controlled, double-blind, randomized trials of medication for the treatment of acute manic episode and the prevention of manic depressive episode that were part of a registration dossier submitted to the regulatory authority of the Netherlands, the Medicines Evaluation Board, between 1997 and 2003, were reviewed for occurrence of suicide and attempted suicide. RESULTS: In 11 placebo-controlled studies of the treatment of acute manic episode, including 1,506 patients (117 person-years) in the combined active compound group and 1,005 patients (71 person-years) in the combined placebo group, no suicides and no suicide attempts occurred. In four placebo-controlled studies of the prevention of manic depressive episode, including 943 patients (406 person-years) in the combined active compound group and 418 patients (136 person-years) in the combined placebo group, two suicides (493 100,000 person-years of exposure) and eight suicide attempts (1,969 100,000 person-years of exposure) occurred in the combined active compound group, but no suicides and two suicide attempts (1,467 100,000 person-years of exposure) occurred in the combined placebo group. CONCLUSIONS: Concern about greater risk of suicide or attempted suicide in the placebo group should not be an argument against the conduct of placebo-controlled trials for these indications, provided that appropriate precautions are taken.