What are the pharmacological treatments for aggression and irritability in Autism Spectrum Disorder (ASD)?

From the Guidelines

Pharmacological management of aggression and irritability in autism should begin with risperidone or aripiprazole, as these are the only FDA-approved medications specifically for this indication. Risperidone is typically started at 0.25-0.5 mg daily and gradually increased to 0.5-3 mg daily divided into two doses, while aripiprazole usually begins at 2 mg daily and can be titrated up to 5-15 mg daily 1. These atypical antipsychotics work by blocking dopamine and serotonin receptors, helping to regulate emotional responses and reduce aggressive outbursts. Some key points to consider when using these medications include:

• Treatment duration should be regularly reassessed, with attempts to taper medication after 6-12 months of stability.
• Common side effects include weight gain, metabolic changes, and sedation, requiring regular monitoring of weight, blood glucose, and lipid profiles 1.
• Alternative medications sometimes used include alpha-2 agonists like guanfacine (0.5-4 mg daily) or clonidine (0.1-0.4 mg daily), which may have fewer metabolic side effects but can cause drowsiness and hypotension.
• Mood stabilizers such as valproate may be considered for treatment-resistant cases. Importantly, pharmacological interventions should always complement behavioral therapies and environmental modifications, not replace them, as combined approaches typically yield better outcomes for managing aggression and irritability in autism 1. Some of the benefits of combining medication with parent training include:
• Moderately more efficacious than medication alone for decreasing serious behavioral disturbance
• Modestly more efficacious for adaptive functioning
• Helps document the effectiveness of the selected medication
• Facilitates the child’s adjustment and engagement with educational intervention.

From the FDA Drug Label

The efficacy of RISPERIDONE in the treatment of irritability associated with autistic disorder was established in two 8-week, placebo-controlled trials in children and adolescents (aged 5 to 16 years) who met the DSM-IV criteria for autistic disorder. Efficacy was evaluated using two assessment scales: the Aberrant Behavior Checklist (ABC) and the Clinical Global Impression - Change (CGI-C) scale. The primary outcome measure in both trials was the change from baseline to endpoint in the Irritability subscale of the ABC (ABC-I) RISPERIDONE, starting at 0.25 mg/day or 0. 5 mg/day depending on baseline weight (< 20 kg and ≥ 20 kg, respectively) and titrated to clinical response (mean modal dose of 1.9 mg/day, equivalent to 0.06 mg/kg/day), significantly improved scores on the ABC-I subscale and on the CGI-C scale compared with placebo.

• Risperidone is a pharmacological treatment for aggression and irritability in Autism Spectrum Disorder (ASD).
• The recommended dose is 0.5-3.5 mg/day on a weight-adjusted basis, with a mean modal dose of 1.9 mg/day.
• Risperidone has been shown to significantly improve scores on the Aberrant Behavior Checklist (ABC) and the Clinical Global Impression - Change (CGI-C) scale compared to placebo 2.

From the Research

Pharmacological Treatments for Aggression and Irritability in Autism Spectrum Disorder (ASD)

• Atypical antipsychtics, such as risperidone and aripiprazole, are probably effective in reducing irritability in individuals with ASD, with moderate-certainty evidence showing a large effect [ 3 ].
• Atypical antipsychtics may also reduce self-injury in individuals with ASD, although the evidence is uncertain [ 3 ].
• ADHD-related medications, such as methylphenidate, may reduce irritability slightly in individuals with ASD, with low-certainty evidence indicating a small effect [ 3 ].
• Neurohormones may have minimal to no effect on irritability in individuals with ASD, with very low-certainty evidence [ 3 ].
• Antidepressants, such as selective serotonin reuptake inhibitors, may not have a clear effect on irritability in individuals with ASD, with low-certainty evidence [ 3 ].

Commonly Used Medications for ASD-Associated Symptoms

• Risperidone and aripiprazole are approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD [ 4 ].
• Methylphenidate and guanfacine are effective for the management of hyperactivity in children with ASD, although they are not FDA-approved for this indication [ 5 ].
• Selective serotonin reuptake inhibitors are often used in clinical practice to target anxiety and compulsions in individuals with ASD, although there is limited evidence to support their use [ 5 ].

Emerging Treatment Options for ASD-Associated Symptoms

• Research into the pathophysiology of ASD has led to new targets for pharmacologic therapy, including the neuroimmune system, the endocannabinoid system, and the glutamatergic neurotransmitter system [ 4 ].
• New classes of drugs with novel mechanisms of action are being developed to improve behavioral symptoms of ASD [ 6 ].