Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study.
Major depressive disorder (MDD) is a severe mental illness with high risk of suicidality. Antidepressant treatment alone is not sufficient for the acute management of risk-taking symptoms of depression. This pilot study was designed to investigate the efficacy of risperidone augmentation to antidepressants in the acute management of suicidality and other core symptoms in MDD with suicidality.



Twenty-four adult men and women diagnosed with MDD (DSM-IV), having a depressive episode with suicidality despite taking an antidepressant, were enrolled in an 8-week double-blind, placebo-controlled study. Subjects were randomly assigned to receive risperidone (0.25-2 mg/day) or placebo while continuing on their antidepressant therapy. Clinical efficacy in suicidality, depressive symptoms, and impulsivity were assessed after treatment with study drugs for 4 days, weekly for 4 weeks, then every other week for 4 weeks. Adverse events were also recorded at each visit. The study was conducted from June 2004 to April 2007.



Risperidone significantly reduced suicidal ideations in MDD patients, and the overall effect of risperidone appeared to be superior to placebo. The effect of risperidone was rapid, with onset at 2 weeks' treatment, and was sustained along the course of 8 weeks' treatment. Furthermore, risperidone demonstrated superiority to placebo in improving other symptoms related to suicidality and having better trial completion rate, and the low dose risperidone was well tolerated by subjects in this study.



Data from this pilot study suggest that risperidone is beneficial as an augmenting treatment in MDD patients who have developed high-risk suicidal ideation during a depressive episode. The antisuicidality effect of risperidone is especially valuable in the acute management of severe depressive symptoms. Although the pilot study is limited by small sample size, the promising results warrant further larger scale investigation in the efficacy of atypical antipsychotics in the treatment of severe depression with suicidality.



clinicaltrials.gov Identifier: NCT00167154.
Reeves
Hollis
H
Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, AL 35294, USA.
Batra
Sachin
S
May
Roberta S
RS
Zhang
Rusheng
R
Dahl
Daniel C
DC
Li
Xiaohua
X
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012309:Risk-Taking; D018967:Risperidone / Q000627:therapeutic use*; D013406:Suicide, Attempted / Q000706:statistics & numerical data*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018967:Risperidone