Atypical Antipsychotics to Manage Behavioral Symptoms in Autism Spectrum Disorder

Are atypical antipsychotics effective and safe for treating behavioral symptoms in people with autism spectrum disorder (ASD)?

In children with ASD, treatment with risperidone or aripiprazole for 3 months may reduce irritability, obsessive-compulsive symptoms, and inappropriate speech. There is insufficient evidence to determine whether these drugs are effective in adults.¹ (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

ASD is a lifelong neurodevelopmental disorder affecting approximately 1% of the global population; it is characterized by impairment of social interaction and communication, along with restricted or repetitive behaviors, interests, or activities.² People with ASD frequently lack access to high-quality mental health care within communities and receive ineffective residential, employment, financial, and social support services.³ Pharmacotherapy is widely used to help manage challenging behaviors such as impulsivity, irritability, self-injury, and aggressiveness.^4,5 Currently, the US Food and Drug Administration has approved only two atypical antipsychotic drugs—risperidone and aripiprazole—for the treatment of irritability in children and adolescents up to age 17 years with ASD.⁵

This Cochrane review included 17 randomized controlled trials (N = 1,027).¹ Only one of the studies exclusively analyzed an adult population (n = 31); participants were an average age of 28.1 years. Included studies compared the use of atypical antipsychotic drugs with placebo or a different atypical antipsychotic in patients with ASD. When applicable, outcomes were evaluated based on validated instruments. The primary outcome analyzed was improvement in irritability as rated by the Aberrant Behavior Checklist (ABC)–Irritability subscale (each item is scored on a 4-point Likert scale for caregiver assessment of irritable behaviors ranging from 0 [not a problem] to 3 [the problem is severe]; total scores range from 0 to 45 points, with higher scores indicating worse symptoms).^1,6 Secondary outcomes included obsessive-compulsive behaviors as rated by the Children’s Yale-Brown Obsessive-Compulsive Scale (a symptom checklist and 6-point severity rating scale in which higher scores indicate greater severity, 0–20 points in total) and inappropriate speech as rated by the ABC-Inappropriate Speech subscale (0–12 points in total, with higher scores indicating worse symptoms).^1,7 Additional outcomes (eg, aggression, weight gain, extrapyramidal symptoms) were examined. The studies used varying regimens of each antipsychotic drug.

Treatment with risperidone or aripiprazole compared with placebo reduced irritability at 3 months in children with ASD, based on low-certainty evidence (risperidone: mean difference [MD] = −7.89; 95% CI, −9.37 to −6.42; aripiprazole: MD = −6.25; 95% CI, −7.62 to −4.91).¹ Lurasidone (Latuda) did not reduce irritability vs placebo (moderate-certainty evidence). Compared with placebo, aripiprazole improved obsessive-compulsive symptoms at 3 months (MD = −1.36; 95% CI, −2.45 to −0.027; low-certainty evidence), and aripiprazole and risperidone improved inappropriate speech at 3 months (MD = −1.44; 95% CI, −2.11 to −0.77; low-certainty evidence); however, these improvements were not quite clinically meaningful. The evidence was insufficient to determine the effect of these treatments on aggression, or whether they were associated with weight gain or extrapyramidal symptoms. There were no studies longer than 3 months that showed statistical or clinical significance.

Many of the studies were underpowered.¹ Moreover, this review noted that the studies were not uniform in clinical procedures or study methods; individual responses of study participants varied. For these reasons, there is limited confidence in the clinical significance of these findings. Furthermore, there are not enough studies to determine the effect of these treatments in adults with ASD. More robust trials with larger sample sizes and longer follow-up periods are needed.