Citalopram Adjunctive to Stimulant May Be Effective for Youth With Chronic Irritability

caucasian little girl having a tantrum
Youth who do not respond to stimulant medication for chronic severe irritability may benefit from the addition of citalopram.

Adjunctive citalopram (CTP) was effective treatment for chronic severe irritability in youth with an inadequate response to stimulant medications alone, according to trial data published in the Journal of the American Academy of Child and Adolescent Psychiatry.

Investigators conducted a double-blind randomized placebo-controlled trial of adjunctive CTP with methylphenidate (MPH) in the treatment of chronic severe irritability in youth. Following a lead-in phase of open treatment with MPH, 53 youth (age 7 to 17 years) with severe mood dysregulation were randomly assigned to receive either adjunctive citalopram (CTP+MPH; n=25) or adjunctive placebo (PBO+MPH; n=28) for 8 weeks. The dosing schedule of CTP began at 5 mg daily and could be increased by 5 mg each week to a maximum daily dose of 40 mg. Participants were assessed every week with the Clinical Global Impression–Improvement and Severity (CGI-S) scale. The primary outcome measure was percentage of response based on CGI-S improvement after 8 weeks. An intent-to-treat analysis was conducted to assess the impact of adjunctive CTP on severe irritability.

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Of 53 initial enrollees, 41 completed the trial. The average citalopram dose achieved was 28.33 mg/day (range, 5 to 40 mg/day). At week 8, a significantly higher percentage of patients assigned to CTP+MPH achieved response (35%) compared with patients in the PBO+MPH condition (6%) (odds ratio, 11.70; 95% CI, 2.00-68.16; P =.006). The group-by-week interaction for the estimated percentage of response over 8 weeks was significant (P =.006), as was the group-by-week interaction for the CGI-S (P =.046). However, no differences in functional impairment, depressive symptoms, and anxiety symptoms were observed between groups at the end of the trial. Adverse events were rare and observed with similar frequency across study conditions.

Despite a smaller than anticipated sample size, these data support the efficacy and tolerability of adjunctive CTP in the treatment of chronic severe irritability in youth who do not respond to stimulants alone. Further research in a larger cohort is necessary to confirm these findings.


Towbin K, Vidal-Ribas P, Brotman MA, et al. A double-blind randomized placebo-controlled trial of citalopram adjunctive to stimulant medication in youth with chronic severe irritability [published online May 22, 2019]. J Am Acad Child Adolesc Psychiatry. doi:10.1016/j.jaac.2019.05.015