Augmentation With Citalopram for Suicidal Ideation in Middle-Aged and Older Outpatients With Schizophrenia and Schizoaffective Disorder Who Have Subthreshold Depressive Symptoms: A Randomized Controlled Trial

Objective: To examine the effects of citalopram augmentation of antipsychotics on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms.

Method: In this placebo-controlled trial conducted from September 1, 2001, to August 31, 2007, 198 outpatients ≥’ ‰40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were randomly assigned to flexible-dose citalopram (n’ ‰=’ ‰104) or placebo (n’ ‰=’ ‰94) augmentation of their antipsychotic for 12 weeks. Depression was measured with the Hamilton Depression Rating Scale (HDRS) and Calgary Depression Rating Scale (CDRS). Primary suicidal ideation measures were the Clinical Global Impressions-Severity of Suicide scale (CGI-SS) and the InterSePT Scale for Suicidal Thinking (ISST); secondary outcomes were the Scale for Suicidal Ideation (SSI), Beck Hopelessness Scale (BHS), HDRS item 3, and CDRS item 8.

Results: Compared to placebo, at the final visit, citalopram was associated with lower BHS scores (4.21 vs 4.98; P’ ‰<‘ ‰.05) and lower likelihood of having suicidal ideation on the ISST (17.7% vs 38.7%; P’ ‰<‘ ‰.005) and HDRS item 3 (14.4% vs 22.6%; P’ ‰<‘ ‰.05). Among the 114 participants with no baseline suicidal ideation, there were no significant differences between citalopram and placebo regarding “emergent” ideation on either primary outcome. Among the 55 participants with baseline suicidal ideation, fewer treated with citalopram had endpoint ideation on the ISST (28.6% vs 66.7%; P’ ‰<‘ ‰.05). Significantly more depression responders than nonresponders went from having baseline suicidal ideation to no suicidal ideation on both the ISST (75.0% vs 31.4%; P’ ‰<‘ ‰.05) and CGI-SS (84.6% vs 31.3%; P’ ‰<‘ ‰.05).

Conclusions: Treatment-emergent suicidal ideation was no more common with citalopram than placebo. In participants with baseline suicidal ideation, citalopram reduced suicidal ideation, especially in those whose depressive symptoms responded to treatment.

Trial Registration: clinicaltrials.gov Identifier: NCT00047450

J Clin Psychiatry 2010;71(7):915-922

Submitted: September 10, 2009; accepted November 3, 2009.

Online ahead of print: March 9, 2010 (doi:10.4088/JCP.09m05699gre).

Corresponding author: Sidney Zisook, MD, University of California San Diego, Department of Psychiatry, 3350 La Jolla Village Drive, San Diego, CA 92161 ([email protected]).