Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial

Abstract

Autism is associated with activation of the inflammatory response system. This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. Significant time × treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P < 0.001), Lethargy/Social Withdrawal (F (1.948, 74.032) = 16.811, P < 0.001), and Stereotypic Behavior (F(1.742, 66.198) = 12.104, P < 0.001), but not for Hyperactivity/Noncompliance (F (2.564, 97.424) = 1.469, P = 0.232), and Inappropriate Speech subscales (F (1.607, 61.075) = 0.173, P = 0.794). By week 10, patients in the celecoxib group showed significantly greater improvement in the Irritability (P < 0.001), Lethargy/Social Withdrawal (P < 0.001), and Stereotypic Behavior (P < 0.00) but not in Hyperactivity/Noncompliance (P = 0.202) and Inappropriate Speech (P = 0.802) subscales than the placebo group. Complete response was achieved by four (20 %) patients in the placebo group and 11 (55 %) patients in the celecoxib group (χ (2) (1) = 5.227, P = 0.022). Frequency of side effects was similar between the two groups. Combination of risperidone and celecoxib was superior to risperidone alone in treating irritability, social withdrawal, and stereotypy of children with autism. (Registration, www.irct.ir ; IRCT138711091556N2).