Fragile X syndrome (FXS) is the most common inherited form of developmental disability and most common single gene cause of autism. Persons with FXS frequently exhibit irritable behavior marked by aggression, self-injury, and severe tantrums. Despite frequent clinical use of atypical antipsychotic drugs to target this behavioral cluster, no systematic trials to date have assessed the efficacy and safety of these drugs in persons with FXS.

We conducted a prospective open-label 12-week trial of aripiprazole in 12 persons aged 6–25�years (mean age, 14.3�years) with FXS who were free of concomitant psychoactive drugs.

Aripiprazole use (mean dose, 9.8�mg/day) was associated with treatment response (defined by a Clinical Global Impressions-Improvement scale score of much improved or very much improved and a ≥25% improvement on the Aberrant Behavior Checklist-Irritability subscale) in 10 of 12 (87%) persons. Two individuals (13%) discontinued aripiprazole prior to study completion due to adverse events. One discontinuation was due to akathisia, mild drooling, and mild tiredness and the other due to moderate tiredness and moderate drooling. No significant changes in vital signs including weight or laboratory measures occurred during treatment with aripiprazole.

Aripiprazole was generally safe and well tolerated and was associated with significant improvement in irritable behavior. Given these findings, a double-blind, placebo-controlled study of aripiprazole in FXS is warranted.