Antipsychotics Most Common Prescription for Aggressive Behaviors in Fragile X Patients, Study Reveals

Treatment for irritability, aggression, agitation and self-injury (IAAS) behaviors in people with fragile X syndrome most often includes antipsychotics, a new has study found.

The research, “Pharmacologic Interventions for Irritability, Aggression, Agitation and Self‑Injurious Behavior in Fragile X Syndrome: An Initial Cross‑Sectional Analysis,” was published in the Journal of Autism and Developmental Disorders. 

IAAS behaviors affect as many as half of all people with fragile X syndrome, decreasing quality of life for those affected and those around them. Although there currently aren’t approved medications for these behaviors in fragile X specifically, therapeutics can be prescribed off-label.

To find out how these medicines are being prescribed, researchers analyzed medical data of 828 people with fragile X syndrome within the Fragile X Online Registry with Accessible Research Database (FORWARD) database. Of these, 415 (50.1%) had documented IAAS behaviors, and of those 415, 180 (43.5%) were on medication for such behaviors.

The researchers first compared the patients who were being treated for IAAS behaviors to those who had IAAS behaviors but weren’t being given medication. This was done to determine which clinical factors make a person with fragile X-related IAAS behaviors more likely to need medicine.

Patients who were on medication were significantly older (average age 14.4 vs. 10.4) and were significantly more likely to be male (90.6% vs. 81.2%) and to have a lower IQ (average scores 45.4 vs. 54.6).

“Increased use of psychoactive drugs in older youth with IAAS may (…) indicate increased reliance on medication use versus behavioral and other non-pharmacological interventions with age; may be a refection of potential family reluctance to medicate young children; and may relate to concern that, as children grow, the signifcance and impact of aggressive behavior may be more concerning,” the researchers wrote.

Additionally, more patients on medication were diagnosed with autism spectrum disorder in addition to fragile X (65.9% vs. 50.2%), had anxiety (92.6% vs. 83.7%), and were hypersensitive to sensory stimuli (54.9% vs. 40.9%).

Among the medications that were being prescribed, most were anti-psychotics: these accounted for 63% of all drugs prescribed, and 71% of the treated patients were taking this class of medication. The most common were risperidone and aripiprazole; together, these anti-psychotics accounted for more than half of the medications prescribed.

“The frequent use of aripiprazole and risperidone targeting IAAS in [fragile X] indicates potential efectiveness of these drugs in the disorder, but also the fact that these drugs are FDA-approved for treating irritability associated with ASD points to likely effectiveness, given that [fragile X] is one cause of ASD,” the researchers explained.

The second-most common class of medications was selective serotoinin reuptake inhibitors (SSRIs, 13.4%); the most common of these was sertraline (Zoloft, 6.94%). Other medication types included stimulants, antidepressants, mood-stabilizers, and anxiolytics.

The majority of treated patients (62.8%) did not have any reported side-effects related to their medications. Of those that were reported, the most common were weight gain (14.4% of subjects) and sedation (8.33%). Other reported side-effects included tremors, headache, dizziness, insomnia, and gastrointestinal issues.

“Future work using the longitudinal natural history of the FORWARD project should allow for analysis of long-term drug treatment of various target symptoms, more specifc evaluation of each behavior within the IAAS symptom category, and more extensive analysis of drug tolerability over time,” the researchers concluded.