What is the first‑line medication for aggression (hitting) in children and adolescents with autism spectrum disorder and attention‑deficit/hyperactivity disorder?

First-Line Medication for Aggression in Children with Autism and ADHD

Risperidone (0.5-3 mg/day) or aripiprazole (5-15 mg/day) are the first-line medications for aggression and hitting in children with both autism spectrum disorder and ADHD, with risperidone and aripiprazole being the only FDA-approved medications specifically for irritability associated with autism. 1, 2

FDA-Approved Treatment Options

Both risperidone and aripiprazole have FDA approval for treating irritability associated with autistic disorder in children ages 5-17 years, including symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. 2 These are the only medications with this specific indication. 1

Risperidone Dosing and Efficacy

• Target dose range: 0.5-3 mg/day, with most children responding at 1-2 mg/day 1, 3
• Approximately 69% of children show positive response versus 12% on placebo 1, 3
• Start with 0.25 mg/day (if <20 kg) or 0.5 mg/day (if ≥20 kg), increasing every 2 weeks by the same increment 3
• Clinical improvement typically begins within 2 weeks of reaching therapeutic doses 1, 3
• No additional benefit above 2.5 mg/day, with increased adverse effects at higher doses 1, 3

Aripiprazole Dosing

• Target dose range: 5-15 mg/day 1
• Both medications show similar efficacy for ADHD symptoms and aggression in children with comorbid ASD and ADHD 4
• Aripiprazole may have advantages regarding prolactin elevation (decreased levels versus increased with risperidone) 4

Critical Monitoring Requirements

Metabolic Monitoring for Risperidone

• Weight, height, BMI: at baseline, each visit for first 3 months, then monthly 1, 3
• Fasting glucose and lipid panel: at baseline, 3 months, then annually 1, 3
• Blood pressure: at baseline, 3 months, then annually 1, 3
• Prolactin levels periodically, especially if clinical signs develop 1, 3
• Liver function tests periodically during maintenance 1, 3
• Clinical assessment for extrapyramidal symptoms at each visit 1, 3

Common Adverse Effects

• Weight gain occurs in 36-52% of patients and is the most concerning long-term side effect 3, 5
• Somnolence/drowsiness in 52% of patients 3
• Increased appetite, fatigue, and drooling are common 3
• Extrapyramidal side effects occur more frequently than placebo (RR 2.36) 5

Integration with ADHD Treatment

Consider addressing ADHD symptoms first or concurrently with methylphenidate, as stimulants remain first-line for ADHD even in autism. 6, 3 Methylphenidate shows efficacy in 49% of children with ASD versus 15.5% on placebo. 1, 3

Post-hoc analyses suggest that adding risperidone to a stimulant provides better control of hyperactivity than stimulant alone in children with autism, ADHD, and disruptive behaviors. 3

Stimulant Considerations

• Stimulants are recommended as first-line therapy for ADHD, with non-stimulants as second-line 6
• Methylphenidate has positive effects on conduct disorder and oppositional defiant disorder 6
• Alpha-2 agonists (clonidine, guanfacine) are possible first-line options in comorbid disruptive behavior disorders 6

Essential Behavioral Interventions

Medication should never substitute for behavioral interventions—combining risperidone with parent training is moderately more efficacious than medication alone for decreasing serious behavioral disturbance. 1, 3 Applied Behavior Analysis (ABA) with differential reinforcement strategies and parent training in behavioral management should be implemented alongside pharmacotherapy. 1, 3

Treatment Algorithm

1. Start risperidone or aripiprazole as first-line for aggression/hitting 1, 2
2. Simultaneously implement or continue behavioral interventions and parent training 1, 3
3. Consider methylphenidate for ADHD symptoms, either before or concurrent with antipsychotic 6, 3
4. Titrate slowly over 2-week intervals to minimize side effects 3
5. Stop dose escalation if adequate control achieved at 1-2 mg/day risperidone or equivalent aripiprazole dose 1, 3
6. Reassess if no improvement by 2 mg/day risperidone, as higher doses unlikely to help 3

Common Pitfalls to Avoid

• Rapid dose escalation increases sedation risk without improving efficacy 3
• Exceeding 2.5 mg/day risperidone provides no additional benefit with more adverse effects 1, 3
• Inadequate metabolic monitoring can miss significant weight gain and metabolic complications 1, 3
• Using medication without behavioral interventions reduces overall efficacy 1, 3
• Failing to address ADHD symptoms with appropriate stimulant therapy when indicated 6, 3