What is the current evidence for the effectiveness of naltrexone (opioid receptor antagonist) in a 13-year-old patient with Autism Spectrum Disorder (ASD) and self-injurious behavior?

Naltrexone for Self-Injurious Behavior in a 13-Year-Old with Autism Spectrum Disorder

Naltrexone may be considered as a second-line pharmacological option for self-injurious behavior in this adolescent with ASD, but only after behavioral interventions and first-line medications (risperidone or aripiprazole) have been inadequately effective. 1, 2

Evidence Quality and Treatment Hierarchy

The American Academy of Child and Adolescent Psychiatry guidelines establish that behavioral interventions, specifically Applied Behavioral Analysis with functional behavioral assessment, must be the first-line treatment for self-injurious behavior in ASD, with pharmacotherapy reserved for severe cases or when behavioral interventions alone are insufficient. 1, 3

For pharmacological management of self-injurious behavior and irritability in ASD:

• Risperidone (0.5-3.5 mg/day) and aripiprazole (5-15 mg/day) are FDA-approved first-line agents with demonstrated large effect sizes in controlled trials for irritability, aggression, and self-injury in children aged 6-17 years. 1, 2
• Combining medication with parent training is moderately more efficacious than medication alone for decreasing serious behavioral disturbance. 1, 2

Naltrexone-Specific Evidence

Efficacy Data

The evidence for naltrexone in pediatric ASD with self-injurious behavior shows mixed and modest results:

• Historical controlled trials from the 1990s demonstrated that naltrexone (0.5-1 mg/kg/day) showed only a positive trend (not statistically significant) for self-injurious behavior reduction in 41 children aged 3-8 years. 1
• A 2015 systematic review found that 77% (98/128) of children showed statistically significant improvement in irritability and hyperactivity symptoms, but there was insufficient evidence that naltrexone impacted core features of autism or specifically self-injury in the majority of participants. 4
• A quantitative synthesis of 86 subjects found that 80% showed some improvement in self-injurious behavior, with 47% achieving ≥50% reduction, though this included both children and adults. 5

Critical Limitations

Important contradictory evidence exists: A rigorous double-blind, placebo-controlled study in 32 mentally retarded adults with autism and/or self-injurious behavior found that naltrexone failed to have therapeutic effects and actually increased stereotypic behavior. 6

The evidence suggests that naltrexone may benefit only a subgroup of children with abnormal endorphin levels, and identifying these characteristics must become a priority before widespread use. 4

Dosing and Administration

If naltrexone is pursued after first-line treatments fail:

• Dose: 0.75-1.0 mg/kg/day (typical range based on pediatric studies). 1, 7, 8
• Start at 0.75 mg/kg/day, as higher initial doses (1 mg/kg) may cause transitory increases in negative behavior. 7
• Formulation challenge: Naltrexone is only available in 50 mg tablets in most countries, requiring compounding to an oral suspension for appropriate pediatric dosing. 7

Side Effects and Monitoring

• Common side effects are mild and transient: sedation (especially at treatment onset), restlessness, and moderate constipation. 1, 7, 8
• Behavioral side effects are typically mild and self-limited. 8
• The bitter taste of tablets presents administration challenges in children. 8

Clinical Algorithm for This Patient

1. First, ensure adequate behavioral intervention trial: Functional behavioral assessment with ABA-based interventions, functional communication training, and parent training must be implemented with sufficient intensity. 1, 3

2. Second, trial first-line pharmacotherapy: Risperidone or aripiprazole should be optimized (target dose risperidone 1-2 mg/day or aripiprazole 5-15 mg/day) in combination with behavioral interventions before considering naltrexone. 1, 2

3. Third, consider naltrexone only if: Self-injurious behavior remains severe despite optimized first-line treatment, poses risk of serious physical harm, and prevents participation in therapeutic interventions. 1, 3

4. Obtain informed consent discussing the limited and mixed evidence, off-label use in this age group, and need for compounded formulation. 7

5. Monitor response using standardized rating scales (Aberrant Behavior Checklist, Clinical Global Impressions) and direct observation of self-injurious behavior frequency and severity. 1, 8

Critical Pitfalls to Avoid

• Do not use naltrexone as first-line treatment before implementing intensive behavioral interventions and trialing FDA-approved medications (risperidone/aripiprazole). 1, 2, 3
• Do not assume naltrexone will work for all patients with self-injury—the evidence suggests only a subgroup responds, likely those with opioid system abnormalities. 4
• Do not overlook treatable comorbidities (depression, anxiety, sleep disorders) that may manifest as increased self-injury. 3
• Ensure adequate formulation is available, as standard tablets are not appropriate for pediatric dosing. 7