Aripiprazole Improved Irritable Behavior in Patients With Fragile X Syndrome, Phase 2 Study Shows

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

Share this article:

Share article via email
CRISPR-Gold gene editing

Irritable behavior in patients with fragile X syndrome significantly improved after receiving aripiprazole, an antipsychotic medication previously approved by the U.S. Food and Drug Administration (FDA) to treat other psychotic conditions.

The study, “A prospective open-label of aripiprazole in fragile X syndrome,” was published in Psychopharmacology.

Fragile X syndrome (FXS) is the most common heritable form of developmental disability and also is the most frequent single gene cause of autism spectrum disorders (ASDs).

Besides developmental disability and characteristic physical features, individuals affected by fragile X often exhibit anxiety-related symptoms, attention-deficit or hyperactivity disorder-like symptoms, and aggressive or self-injurious behaviors.

Aggressive and self-injurious behaviors seem to have a tendency to increase as patients age: 20 percent of young boys with fragile X exhibit these symptoms, while up to 50 percent of adolescents and young adults manifest such behaviors, usually requiring medical treatment.

Although antipsychotic drugs designed to specifically target this set of behaviors have been tested in a clinical setting, no systematic trials had addressed the safety and effectiveness of these medications in patients with fragile X.

Specifically, the antipsychotic aripiprazole, which can minimize irritability associated with autistic disorders in children and adolescents, had never been tested in the context of fragile X.

Researchers designed a clinical study to determine the effectiveness and tolerability of aripiprazole in children and adolescents with fragile X.

The open-label, Phase 2, 12-week trial (NCT00420459) enrolled 12 children and adolescents between the ages of 5 and 35 with fragile X who were not under medication.

During the first week of the study, subjects received 2.5 mg of aripiprazole daily. The dosage was then increased to a maximum of 20 mg a day for the first eight weeks in cases where the optimal clinical response had not been reached and no adverse side effects emerged. When optimal dosage was established, patients received it for four weeks.

Aripiprazole treatment at a mean dosage of 9.8 mg a day was associated with a positive treatment response regarding irritability symptoms (aggression, self-injury and severe tantrums) in 87 percent of the subjects.

Two individuals failed to complete the study due to adverse side effects: one due to akathisia (the inability to stay still), mild drooling, and mild tiredness, and the other due to moderate tiredness and moderate drooling.

Overall, aripiprazole was well-tolerated by patients, with no serious side effects registered during the study.

“This report represents the first systematic study of any antipsychotic drug in persons with FXS. The findings of improved irritable behavior with use of aripiprazole are consistent with reports from use of the drug in persons with ASDs,” the authors wrote.

Although results are promising, the study was not without its limitations. The lack of placebo control subjects meant disease outcomes were more prone to be biased, while the small sample size and relative short duration of the study limited assessments on long-term treatment effectiveness and tolerability.

To overcome these limitations, investigators believe a double-blind, placebo-controlled study of aripiprazole in patients with fragile X is necessary.