Drug Refractory Irritability in Persons with Autism Spectrum Disorders

Background: Of the many reasons patients with Autism Spectrum Disorders (ASD) seek out mental health care, irritable behavior (irritability) marked by aggression, self-injury, and severe tantrums may be the most dangerous to patients, caregivers and society at large. Currently, two medications, risperidone and aripiprazole, are United States Food and Drug Administration (FDA) approved for use in the treatment of irritability in persons with ASD. Despite these drug approvals and significant recent drug research targeting irritability in ASD, little is known about how often irritability becomes refractory to first line drug treatment in this population.  

Objectives: We sought to better understand the large number of patients with ASD who presented to our clinic with irritability by identifying variables that would predict whether these patients eventually became refractory to drug treatment.  We define the term Drug Refractory Irritability (DRI) by the presence of continuing irritable behavior requiring treatment adjustment despite failure of clinically adequate (duration at least 4 weeks, dosing within range of normal clinical use if such dosing tolerable) treatment trials of both aripiprazole and risperidone or failure of at least three previous clinically adequate drug trials (one trial must have included aripiprazole or risperidone).

Methods: The study will review the medical records of 200 consecutive patients evaluated for treatment at the Christian Sarkine Autism Treatment Center. Patients were seen from January 2005 through August 2011 and were diagnosed using Diagnostic and Statistical Manual, 4^th Edition, Text Revision criteria for an ASD by a board certified child and adolescent psychiatrist with extensive experience with this population (CAE).

Results: In a preliminary analysis of the first 62 consecutive patients (age range 4-22 years) with a diagnosis of an ASD, 77% (36 males; 12 females) initially presented with the chief complaint of irritability. On initial presentation to our clinic 27% (n=17) of these patients already met criteria for DRI.  Among these patients, an additional nine patients (15%) developed DRI during the course of ongoing treatment. Future work will include a statistical analysis of potential variables predictive of the development of DRI including factors such as age, gender, presence of comorbid intellectual disability, specific ASD diagnosis, and potential known cause of ASD.

Conclusions: Despite the availability of first line FDA approved drug treatment, the results suggest that a large proportion of ASD patients presenting with irritability may go on to experience DRI.  Future research investigating appropriate treatment approaches to patients with DRI is indicated.