Review of: Reddihough DS et al, JAMA 2019;322(16):1561–1569

Restrictive, repetitive, and stereotypical behaviors in children and adolescents with autism spectrum disorder (ASD) are a common concern, and there are no FDA-approved medications for their treatment. We know that fluoxetine is effective in the treatment of obsessive-compulsive disorder in children and adolescents (Geller DA et al, Am J Psychiatry 2003;160(11);1919–1928), and even though our best understanding is that this phenomenon is different from OCD, it is nevertheless common for clinicians to try to treat symptoms that seem similar. Given that, would fluoxetine help these OCD-like symptoms in ASD patients? This study focused on this question.

The authors used a randomized, placebo-controlled design and enrolled children and adolescents with a history of ASD and a score of more than 5 on the CYBOCS-PDD scale (Children’s YBOCS modified for PDD). Seventy-five participants aged 7.5 to 18 years received fluoxetine, while 71 age-matched patients received placebo. The dose of fluoxetine was titrated over 3 weeks to a maximum of 20–30 mg (depending on weight) and continued for a total of 16 weeks. Dosage was kept on the lower side to avoid behavioral activation in this vulnerable population. Over 40% of participants in both groups experienced adverse effects, but more patients dropped out in the fluoxetine group than the placebo one (41% vs 30%).

While some individuals seemed to benefit, due to the high variability of the group outcomes, neither fluoxetine nor placebo led to significant symptom reduction, with no additional clarity when factors such as gender and baseline CYBOCS-PDD scores were controlled. No differences were noted in secondary outcomes either (eg, CGI scores).

CCPR’s Take
Based on this fairly small study, we have no research to be confident that low dosages of fluoxetine will reliably treat perseveration in ASD. Fluoxetine and other SSRIs have a similarly unproven role in treating anxiety and depression in autism, which—as is often the case in ASD—leaves us guessing, trying, and watching for side effects such as behavioral activation.