Side-effects of SSRIs disrupt multimodal treatment for pediatric OCD in a randomized-controlled trial

Activation Syndrome (AS) is a side-effect of antidepressants consisting of irritability, mania, self-harm, akathisia, and disinhibition. The current study was conducted to analyze how AS may hinder treatment outcome for multimodal treatment for children and adolescents with Obsessive-Compulsive Disorder.

Fifty-six children or adolescents were recruited at two treatment sites in a double-blind randomized-controlled trial where participants received Cognitive-Behavioral Therapy and were randomized to slow titration of sertraline, regular titration of sertraline or placebo.

Using a recently developed measure of AS, results suggested that higher average levels of irritability, akathisia, and disinhibition significantly interfered with treatment response and explained 18% of the variance in obsessive-compulsive symptoms during treatment. Interestingly, only session-to-session increases in irritability resulted in a session-to-session increase in obsessive-compulsive symptoms. The observed results were unchanged with the addition of SSRI dosage as a covariate.

Results provide empirical support for the proposed hypothesis that AS may hinder multimodal treatment outcome for pediatric OCD. These findings suggest that dosage changes due to AS do not explain why those with higher AS had worse multimodal outcome. Other possible mechanisms explaining this observed disruption are proposed, including how AS may interfere with Cognitive-Behavioral Therapy.