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

• Published in: The American journal of psychiatry 2005-04, Vol.162 (4), p.799-802
• Main Authors: Storosum, Jitschak G., Wohlfarth, Tamar, Gispen-de Wied, Christine C., Linszen, Don H., Gersons, Berthold P.R., van Zwieten, Barbara J., van den Brink, Wim
• Format: Article
• Language: English
• Subjects: Acute Disease; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - prevention & control; Bipolar Disorder - psychology; Clinical trials; Clinical Trials Data Monitoring Committees - standards; Double blind randomized controlled trials; Double-Blind Method; Drug toxicity and drugs side effects treatment; Drugs; Ethics, Research; Haloperidol - therapeutic use; Health risk assessment; Humans; Lithium - therapeutic use; Mania; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Netherlands; Pharmacology. Drug treatments; Placebo effect; Placebos; Prevention; Psychiatry; Randomized Controlled Trials as Topic - ethics; Randomized Controlled Trials as Topic - standards; Risk assessment; Risk Factors; Suicide; Suicide - psychology; Suicide - statistics & numerical data; Suicide, Attempted - psychology; Suicide, Attempted - statistics & numerical data; Suicides & suicide attempts; Treatment
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.162.4.799

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.