Review of: Moazen-Zadeh E et al, J Child Adolesc Psychopharmacol 2018;28(1):82–89.

Disorders of lipid metabolism—specifically inefficient metabolism of lipids—have been implicated as part of the metabolic complexity in children with autism spectrum disorder. Research points to the neuroprotective effects of simvastatin over other statins, due to its greater ability to cross the blood-brain barrier. But does that neuroprotection translate to differences in behavior?

This 10-week randomized, double-blind, placebo-controlled trial compared simvastatin to placebo as adjunctive treatment to risperidone for irritability in children meeting criteria for DSM-IV-TR autistic disorder (AD).

All participants scored ≥ 12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale, and therefore met criteria for treatment of irritability with medications. The ABC-C scale rates children on 58 items arranged in 5 behavioral abnormality subscales. In total, 66 children ages 4–12 years completed the trial and were randomized to receive risperidone and either simvastatin or placebo. Risperidone target dose was 1 mg/day if < 20 kg and 2 mg/day if ≥ 20 kg. Simvastatin was started concurrently with risperidone and was dosed at 20 mg per day for children < 10 years old, and 40 mg per day if ≥ 10 years old. The ABC-C rating scale was assessed at baseline, for week 5, and week 10.

The primary outcome was change in the ABC-C irritability subscale, which showed a significant difference in favor of the simvastatin arm at week 10 (-3.45, p = 0.083). Secondary outcomes were the other four subscales, for which there was a significant improvement in the simvastatin group over placebo only in the hyperactivity/noncompliance subscale (-4.27, p = 0.001).

The other subscales that represent the core deficits of AD (lethargy/social withdrawal, stereotypic behavior, and inappropriate speech) showed no significant differences. There was also no significant difference in any adverse events between the groups. The more common side effects across both groups were increased appetite (25.8%), myalgia (13.6%), nausea (12.1%), and headache (12.1%).

CCPR’s take
The results of this study are promising, but it is only the first of its kind to evaluate simvastatin treatment in this clinical setting. Since long-term benefits or adverse effects have not been established, it’s too early to recommend this approach. As in studies of anti-inflammatory interventions, behavioral symptoms may be improved, but the core symptoms of autism remain unchanged.