title: Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Medicines Evaluation Board of the Netherlands, Kalvermarkt 53, PO-BOX 16229, 2500 BE Den Haag, The Netherlands. JG.Storosum@CBG-MEB.nl
authors.forename: Jitschak G
authors.initials: JG
authors.lastname: Storosum
authors.forename: Tamar
authors.initials: T
authors.lastname: Wohlfarth
authors.forename: Christine C
authors.initials: CC
authors.lastname: Gispen-de Wied
authors.forename: Don H
authors.initials: DH
authors.lastname: Linszen
authors.forename: Berthold P R
authors.initials: BP
authors.lastname: Gersons
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: van Zwieten
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
mesh_terms: D000208:Acute Disease; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000517:prevention & control* / Q000523:psychology; D026661:Clinical Trials Data Monitoring Committees / Q000592:standards; D004311:Double-Blind Method; D032984:Ethics, Research; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D009426:Netherlands; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000941:ethics* / Q000592:standards; D012307:Risk Factors; D013405:Suicide / Q000523:psychology* / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D008094:Lithium; D006220:Haloperidol