What is the role of Risperidone (atypical antipsychotic) in treating Autism Spectrum Disorder (ASD)?

From the Guidelines

Risperidone is a recommended treatment for irritability associated with Autism Spectrum Disorder (ASD) in children and adolescents, particularly when symptoms of aggression, self-injury, and severe tantrums are present, as evidenced by studies such as 1.

Key Points to Consider

• The medication is FDA-approved for this specific use in children and adolescents aged 5-16 years.
• The typical starting dose is 0.25 mg daily for children weighing less than 20 kg and 0.5 mg daily for those weighing more than 20 kg, with gradual increases to an optimal dose range of 0.5-3 mg daily divided into one or two doses, as seen in studies like 1.
• Risperidone works by blocking dopamine D2 and serotonin 5-HT2A receptors in the brain, which helps regulate neurotransmitter activity influencing behavior and mood.
• Common side effects include weight gain, increased appetite, drowsiness, fatigue, drooling, tremor, and metabolic changes, necessitating regular monitoring of weight, blood glucose, and lipid levels, as noted in 1 and 1.
• It is crucial to use Risperidone as part of a comprehensive treatment approach that includes behavioral therapies and educational interventions, rather than as a first-line treatment for core ASD symptoms like social communication deficits.

Treatment Approach

• Combining medication with parent training is moderately more efficacious than medication alone for decreasing serious behavioral disturbance and modestly more efficacious for adaptive functioning, as highlighted in 1.
• Treatment duration should be periodically reassessed, with the shortest effective period used to minimize side effects.
• The goal of treatment is to facilitate the child’s adjustment and engagement with educational intervention, making it essential to monitor treatment response through caregiver report, observation of specific behaviors, and the use of objective rating scales, as discussed in 1 and 1.

Side Effects and Monitoring

• Regular monitoring of side effects such as weight gain, increased appetite, and metabolic changes is necessary, as these can impact the child’s health and quality of life, as mentioned in 1 and 1.
• The side effect profile of Risperidone, including headache, somnolence, and asymptomatic increases in prolactin, should be considered when deciding on treatment, as noted in 1.

Comprehensive Care

• Risperidone should be considered after assessments of whether potential contributors to irritability and aggression could be addressed by nonpharmacological means, emphasizing the importance of a comprehensive approach to care, as suggested in 1.

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's role in treating Autism Spectrum Disorder (ASD): Risperidone is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. The recommended dose is titrated to clinical response, with a mean modal dose of 1.9 mg/day in children and adolescents.

• Key benefits: Significant improvement in irritability symptoms, as measured by the Aberrant Behavior Checklist (ABC) and the Clinical Global Impression - Change (CGI-C) scale.
• Target population: Children and adolescents (aged 5 to 17 years) with autistic disorder.
• Dosing: Starting at 0.25 mg/day or 0.5 mg/day, depending on baseline weight, and titrated to clinical response 2.

From the Research

Role of Risperidone in Treating Autism Spectrum Disorder (ASD)

Risperidone, an atypical antipsychotic, plays a significant role in managing irritability associated with Autism Spectrum Disorder (ASD) in children and adolescents. The key aspects of its use are outlined below:

• Efficacy in Reducing Irritability: Studies have shown that risperidone is effective in reducing irritability and other behavioral symptoms associated with ASD 3, 4, 5, 6.
• Approved Indications: In the US, risperidone is approved for the treatment of irritability associated with autistic disorder in children and adolescents aged 5-16 years 3.
• Pharmacokinetic Profile: Risperidone's pharmacokinetic profile supports its use in ASD, with evidence suggesting it acts via dopamine D(2) and serotonin 5-HT(2A) receptor antagonism 4.
• Short-term and Long-term Use: While there is ample evidence supporting the short-term use of risperidone for treating irritability and behavioral problems in ASD, its long-term effects and safety require further investigation 4, 6.
• Comparison with Other Interventions: Risperidone has been compared to other pharmacological and non-pharmacological interventions, with results indicating it is one of the most effective treatments for irritability in ASD, alongside aripiprazole and parent training 7, 5.
• Safety and Tolerability: Risperidone has a clinically manageable tolerability profile, although monitoring is required for aspects such as weight gain, somnolence, and hyperglycemia 3, 4, 5.

Key Considerations for Risperidone Use in ASD

When considering risperidone for the treatment of ASD, the following points are crucial:

• Individual Risk-Benefit Analysis: Each patient's risk-benefit profile should be carefully evaluated before initiating treatment with risperidone 4.
• Monitoring for Adverse Effects: Regular monitoring for potential adverse effects, such as weight gain and metabolic changes, is essential 4, 5.
• Combination Therapy: The potential benefits and risks of combining risperidone with other therapies should be considered, as some novel molecules show promise in augmentation to risperidone 7.