A Double-Blind Randomized Placebo-Controlled Trial of Citalopram Adjunctive to Stimulant Medication in Youth With Chronic Severe Irritability.

Abstract

OBJECTIVE\nDespite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design.\n\n\nMETHOD\nAfter a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. Forty-nine participants - 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria - were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the 8th week of the trial.\n\n\nRESULTS\nAt the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH vs. 6% PBO+MPH; OR=11.70, 95%CI 2.00, 68.16, p=0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms.\n\n\nCONCLUSION\nAdjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone. This trial was registered on ClinicalTrials.gov (Identifier: NCT00794040).