Efficacy and safety of add-on dextromethorphan on irritability in children with ADHD treated with methylphenidate: A randomized double-blind controlled trial.

OBJECTIVE

Converging evidence suggests that childhood irritability is prospectively associated with major depressive disorder. Dextromethorphan has shown efficacious in improving depressive symptomatology in adults. This trial aimed to investigate the efficacy and safety of add-on dextromethorphan on irritability in children with attention-deficit/hyperactivity disorder (ADHD) receiving methylphenidate treatment.

METHODS

This randomized, double-blind, parallel-group trial evaluated dextromethorphan/methylphenidate versus placebo/methylphenidate in patients 7-17 years old with ADHD and comorbid irritability, which defined by the score of the Affective Reactivity Index (ARI) parent-report form ≥6. Patients were randomly assigned to receive optimal dose of methylphenidate and either dextromethorphan or placebo, 30 mg once daily for the first 2 weeks and 60 mg once daily thereafter, for a total of 8 weeks. The primary outcome was the change from baseline to week 8 in the ARI score.

RESULTS

A total of 19 patients were randomized (dextromethorphan, N = 8; placebo, N = 11), and Dextromethorphan was significantly superior to the placebo in reducing the ARI score at Week 2 (-5.82 points vs. -0.32 points; least-squares mean difference - 5.50; 95 % CI -8.13, -2.87), Week 4 (-6.49 points vs. -1.96 points; least-squares mean difference - 4.53; 95 % CI -7.13, -1.94), and Week 8 (-4.98 points vs. -2.21 points; least-squares mean difference - 2.77; 95 % CI -5.29, -0.24). The effects of treatment by time interaction were significant at week 2, week 4, and week 8 (p < 0.001, p < 0.001, and p = 0.015, respectively).

CONCLUSIONS

Adjunctive dextromethorphan might be efficacious in the treatment of irritability in children with ADHD treated with methylphenidate.