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

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00382291.

Keywords: Activation syndrome; Children; Cognitive-behavioral therapy; Obsessive-Compulsive Disorder; Selective serotonin reuptake inhibitors; Side-effects.

Fig. 1

Study flow chart that summarizes recruitment study completion statistics. Reasons for early termination include pharmacy error (PE), suicidal adverse events (SAE), non-suicidal adverse events (AE), and other reasons (e.g., time demand). For more information on the PE, please see the footnote in the discussion section.

Fig. 2

This figure displays average levels of activation syndrome symptoms in each treatment arm over the 18 weeks of treatment (i.e., mean across treatment), as measured by the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP). Scores show that, in general, the regular sertraline titration (RegSert), slow sertraline titration (SlowSert) arms experienced notably more activation syndrome symptoms than the placebo arm. Raw means are displayed, therefore means presented are biased by the number of items in the scale.

Fig. 3

This figure displays average change in obsessive-compulsive symptom severity from the point of randomization, as measured by the gold-standard Children's Yale-Brown Obsessive-Compulsive Scale (CYBOCS). Scores are broken up into a low activation syndrome group (Low AS), medium activation syndrome group (Medium AS), and high activation syndrome group (High AS). These groups were created based on average activation symptoms endorsed throughout treatment.