What medications are used to manage symptoms in individuals with autism?

Medications for Autism Spectrum Disorder

Pharmacotherapy in autism targets specific associated symptoms—particularly irritability, aggression, hyperactivity, and repetitive behaviors—rather than core social communication deficits, with risperidone and aripiprazole being the only FDA-approved medications for irritability in children and adolescents aged 5-17 years. 1, 2

FDA-Approved First-Line Treatments

For Irritability and Aggression

Risperidone and aripiprazole are the only FDA-approved medications for treating irritability associated with autism, including aggression, self-injury, and temper tantrums. 2

• Risperidone: Dose 0.5-3.5 mg/day, starting at 0.25-0.5 mg/day based on weight, with demonstrated efficacy in reducing ABC Irritability subscale scores in multiple RCTs 3, 2
• Aripiprazole: Dose 5-15 mg/day flexibly dosed, with 56% positive response rate at 5 mg versus 35% on placebo 3, 1
• Both medications show significant improvements in irritability, hyperactivity, and stereotypy subscales compared to placebo 1

Critical caveat: Risperidone causes weight gain, increased prolactin, and metabolic side effects; aripiprazole causes somnolence, weight gain, and drooling—these side effects necessitate careful monitoring but should not prevent use when irritability is severe 3

Combining medication with parent training is moderately more efficacious than medication alone for decreasing serious behavioral disturbance, making behavioral intervention essential alongside pharmacotherapy 1

Treatment for ADHD Symptoms

Methylphenidate as First-Line

Methylphenidate should be considered first-line for hyperactivity and inattention in autism, despite lower effect sizes (0.39-0.52) compared to typically developing children with ADHD (0.8-0.9). 3

• Starting dose: 0.3-0.6 mg/kg/dose, 2-3 times daily 1
• Efficacy rate: 49% in children with ASD versus 15.5% on placebo 1
• Approximately 40% of children with intellectual disability and ASD respond to methylphenidate 3
• Side effects mirror those in typical ADHD: appetite suppression and sleep problems 3

Alternative ADHD Medications

• Atomoxetine: Shows modest benefits for hyperactivity with better tolerability profile than stimulants 4
• Alpha-2 agonists (clonidine, guanfacine): Demonstrate efficacy for hyperactivity and stereotyped behaviors, though evidence is limited to small studies 3
• Risperidone as adjunct: Post-hoc analysis suggests adding risperidone to stimulants provides better hyperactivity control than stimulants alone, but use only after stimulant monotherapy fails due to metabolic risks 3

Treatment for Repetitive Behaviors

SSRIs have limited and inconsistent evidence for repetitive behaviors in autism, with concerning tolerability issues in children and adolescents. 4, 5

• Fluvoxamine (2.4-20 mg/day) showed statistically significant decrease in CY-BOCS Compulsions scale in one study 1
• Recent consensus indicates potential harm from SSRIs for repetitive behaviors in children/adolescents with ASD, making them a poor choice despite theoretical rationale 4
• Buspirone shows promise for restrictive behaviors and anxiety, representing a safer alternative to SSRIs 6, 5

Treatment for Comorbid Conditions

Anxiety and Depression

• SSRIs (fluoxetine, sertraline) remain treatment of choice for depression and anxiety based on evidence in typically developing youth, though use cautiously given poor tolerability data in ASD populations 3, 5
• Alpha-2 agonists and beta-blockers are sometimes used for anxiety management 3

Sleep Disturbances

• Melatonin is first-line treatment for sleep disturbances in autism 1, 5
• Sedating antihistamines may improve sleep quality but have limited efficacy evidence 1

Critical Clinical Approach

Before initiating any medication, assess whether potential contributors to target symptoms (irritability, aggression, hyperactivity) could be addressed by nonpharmacological means, including environmental modifications, communication supports, and behavioral interventions 3, 1

Monitoring Requirements

• Regular assessment using standardized rating scales (ABC, CGI-C) is essential 1
• For risperidone: Monitor weight, prolactin, metabolic parameters, and extrapyramidal symptoms 3, 2
• For aripiprazole: Monitor weight, sedation, and metabolic parameters 3
• For stimulants: Monitor appetite, sleep, growth parameters, and cardiovascular status 3

Medications to Avoid

• Long-term benzodiazepines: Unfavorable risk-benefit profile 1
• Oral corticosteroids: Unfavorable risk-benefit profile 1
• SSRIs in children: Poorly tolerated with inconsistent evidence for core ASD symptoms 4, 5

Algorithmic Treatment Approach

1. Identify target symptom domain (irritability/aggression, hyperactivity, repetitive behaviors, sleep)
2. Implement behavioral interventions first or concurrently with medication 1
3. For severe irritability/aggression: Start risperidone 0.25-0.5 mg/day or aripiprazole 2-5 mg/day 3, 2
4. For hyperactivity/inattention: Start methylphenidate 0.3 mg/kg/dose twice daily 3, 1
5. For sleep problems: Start melatonin 1, 5
6. Titrate to clinical response using standardized scales, not subjective impression alone 1
7. Monitor side effects systematically at each visit 3

The goal of medication is to facilitate the child's adjustment and engagement with educational and behavioral interventions, not to sedate or suppress all challenging behaviors 1