What are the FDA-approved medications for treating irritability in autism?

FDA-Approved Medications for Irritability in Autism

Only two medications are FDA-approved for treating irritability associated with autism spectrum disorder: risperidone and aripiprazole. 1, 2

Approved Medications and Their Indications

Risperidone

• FDA approval: For treating irritability associated with autistic disorder in children and adolescents aged 5-17 years 1
• Target symptoms: Aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods 1
• Dosing:
  • Children weighing <20 kg: Start at 0.25 mg/day; can be increased to 0.5 mg/day after 4 days
  • Children weighing ≥20 kg: Start at 0.5 mg/day; can be increased to 1 mg/day after 4 days
  • Further dose adjustments in 0.25-0.5 mg increments at ≥2 week intervals 2
  • Typical effective dose range: 0.5-3.5 mg/day 2

Aripiprazole

• FDA approval: For treating irritability associated with autistic disorder in children and adolescents aged 6-17 years
• Target symptoms: Same as risperidone - tantrums, aggression, self-injurious behavior 3
• Dosing:
  • Starting dose: 2 mg/day
  • Target dose range: 5-15 mg/day 4, 3
  • Mean effective dose in clinical trials: 5.5 mg/day 4

Efficacy Comparison

• Both medications demonstrate significant efficacy in reducing irritability in autism as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale 4, 3
• Head-to-head comparison shows comparable efficacy between aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) 4
• Response rates:
  • Risperidone: 69% positive response vs. 12% on placebo 2
  • Aripiprazole: 56% positive response vs. 35% on placebo 2, 3

Side Effect Profiles

Risperidone

• Common side effects: Weight gain, increased appetite, fatigue, drowsiness, drooling, dizziness 2
• Metabolic effects: Significant weight gain (mean 2.0 kg in 8 weeks), increased risk of metabolic syndrome 1
• Endocrine effects: Prolactin elevation 1
• Neurological effects: Extrapyramidal symptoms, sedation 2

Aripiprazole

• Common side effects: Somnolence, weight gain, drooling, tremor, fatigue, vomiting 2, 3
• Metabolic effects: Weight gain (mean 2.0 kg in 8 weeks) 3
• Neurological effects: Extrapyramidal symptoms (14.9% vs. 8.0% on placebo) 3

Monitoring Recommendations

1. Baseline assessments:

   • Weight and BMI
   • Metabolic parameters (fasting glucose, lipid profile)
   • Prolactin levels (especially for risperidone)
   • Extrapyramidal symptom assessment

2. Ongoing monitoring:

   • Regular weight checks (weekly for first month, then monthly)
   • Metabolic parameters at 3 months and then quarterly
   • Assessment for emergence of extrapyramidal symptoms
   • Evaluation of sedation and cognitive effects

Clinical Decision-Making Algorithm

1. Initial medication selection:

   • For patients with metabolic risk factors or concerns about prolactin elevation: Consider aripiprazole first
   • For patients with more severe irritability: Risperidone may have slightly better efficacy in more severe cases 5
   • For younger children (5-6 years): Risperidone is approved for ages 5+, while aripiprazole is approved for ages 6+

2. Dosing approach:

   • Start at lowest possible dose
   • Titrate slowly based on response and tolerability
   • Target the lowest effective dose to minimize side effects

3. Monitoring response:

   • Assess improvement in target symptoms (aggression, self-injury, tantrums)
   • Consider standardized rating scales (ABC Irritability subscale)
   • Evaluate for side effects at each dose increase

Important Caveats and Considerations

• Weight gain: Not necessary for therapeutic benefit and may actually detract from efficacy 5
• Residual symptoms: Even with optimal treatment, clinically significant symptoms may persist in some patients 3
• Long-term safety: Limited data on long-term safety beyond 6 months in the pediatric autism population 6, 7
• Predictors of response: Higher baseline severity predicts better response to risperidone; comorbid anxiety, hyperactivity, and stereotypy predict worse outcomes 5

Both medications should be used as part of a comprehensive treatment approach, with regular reassessment of the need for continued medication and attempts at dose reduction when clinically appropriate.