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Adverse Effects Reduce Drug Efficacy in OCD

Adverse Effects Reduce Drug Efficacy in OCD


Activating adverse effects of an SSRI were found to interfere with multimodal treatment of OCD in a new study of treatment tolerance and therapeutic response in children and adolescents.1 Higher levels of irritability, akathisia, or disinhibition, but not mania or self-injury of the 5 measured domains of “activation syndrome” (AS), predicted less response than a combination of psychopharmacologic and psychotherapeutic treatment over the 17 weeks of the study. Irritability in particular appeared to interfere with treatment outcome: session-to-session OCD symptom severity increased after the onset of irritability.

“According to our findings, irritability does immediately slow treatment outcome,” lead author Adam Reid told Psychiatric Times. “Irritability can be very difficult for therapists and patients to handle during psychological treatment for OCD,” he explained. “The treatment involves encouraging the youth to conduct anxiety-provoking exposures that are emotionally taxing. . . . While higher levels of mania and suicidality (components of the AS self-injury domain) were not significantly associated with worse outcome, these side effects are more rare and thus a larger sample may be needed to more appropriately study them.”

Validated assessment of activation syndrome

This examination of the dynamics between pharmacotherapy and psychotherapy for OCD was undertaken with the recent availability of the validated, comprehensive assessment measure of AS. The Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP), published in 2013, measures 5 clusters of potential adverse effects: irritability, akathisia, disinhibition, mania, and self-harm.2 With the new measure, the study authors suggest that “clinicians are now better positioned to track AS during SSRI administration and may be more effective at modulating dosage if AS emerges.”

The study population was chosen both for the potential to benefit from multimodal treatment and for being at risk for adverse drug effects. “Due to its frequency of use and the high doses of SSRIs required to treat pediatric OCD, pediatric OCD would be a logical population to investigate how AS may impact multimodal treatment outcome,” Reid and colleagues noted.

Their provision of cognitive-behavioral therapy with exposure and response prevention (CBT-ERP) along with an SSRI antidepressant follows the treatment recommendations of several organizations, including the Academy of Child and Adolescent Psychiatry.

Evaluating adverse effects and efficacy

The double-blind, randomized, controlled trial at 2 OCD specialty clinics assessed 56 children and adolescents who received 17 weeks of CBT-ERP and either placebo or sertraline. CBT-ERP was started at week 4; and medication was initiated in the first week, with dosage increased in either a slow or regular titration from 25 mg daily to 200 mg over 9 weeks. A therapeutic dose, defined as a balance of efficacy and tolerability at up to 150 mg daily, was attained by week 4 with regular titration and by 8 weeks with slow titration. Dosing in both medication arms was adjusted for poor tolerability by delaying titration or by reducing dose.

The TEASAP, a parent-report measure of 38 items scored on a 4-point Likert scale, was completed by a parent at every weekly visit throughout the 17 weeks. The researchers point out that analysis of these weekly measures was baseline- centered; it captured treatment-emergent effects and excluded baseline comorbid symptoms.


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