Fluoxetine is minimally effective for obsessive-compulsive behaviors in children/adolescents with autism spectrum disorders

Reference

Reddihough DS, Marraffa C, Mouti A, et al. Effect of fluoxetine on obsessive-compulsive behaviors in children and adolescents with autism spectrum disorders. A randomized clinical trial. JAMA 2019;322(16):1561-1569.

Synopsis

These investigators identified children and adolescents, aged 7.5 to 18 years, who met the standard diagnostic criteria for ASD. Study eligibility criteria included a score of 6 or greater on the validated Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorders (total score ranging from 0 to 20, with higher scores indicating higher levels of maladaptive behaviors). Participants (N = 146) randomly received (concealed allocation assignment) weight-based dosage and titration of fluoxetine for a total of 16 weeks. The maximum dosage was 20 mg per day for participants who weighed less than 40 kg and 30 mg per day for those who weighed 40 kg or more. The primary outcome was the difference between groups in the total behavior score at 16 weeks, with a difference of 2 considered to represent a clinically important improvement. Individuals masked to treatment group assignment assessed outcomes. Complete data were available for 75% of participants at 22 weeks. Using intention-to-treat analysis, behavioral scores were significantly lower at 16 weeks in the fluoxetine group than in the placebo group (mean difference -2.01; 95% CI, -3.77 to -0.25), with the 95% confidence interval including a clinically unimportant difference. However, the difference between groups became nonsignificant when controlling for sex, verbal ability, and baseline imbalances in aberrant behaviors. Similarly, secondary outcomes using 6 additional emotional and behavior scales also failed to show a difference between groups after controlling for confounding variables. Nearly half of both groups experienced adverse events, including mood disturbance and irritability, nausea and diarrhea, and sleep disorders.