Can lamotrigine (anticonvulsant medication) help stabilize mood in patients with Autism Spectrum Disorder (ASD)?

Lamotrigine for Mood Stabilization in Autism Spectrum Disorder

Lamotrigine should not be used for mood stabilization in autistic patients, as a high-quality randomized controlled trial found no significant benefit for behavioral symptoms of autism, and current guidelines do not recommend it for this indication. 1

Evidence Against Lamotrigine in Autism

The strongest evidence comes from a double-blind, placebo-controlled trial specifically examining lamotrigine in 28 children with autism (ages 3-11 years). 1 This study found:

• No significant improvements in core autism symptoms including stereotypies, lethargy, irritability, hyperactivity, or emotional reciprocity compared to placebo 1
• No improvements in language, communication, socialization, or daily living skills after 12 weeks of treatment 1
• The only positive findings were on parent rating scales, which investigators attributed to expectation bias rather than true drug effects 1

This negative trial directly contradicts the use of lamotrigine for mood stabilization in autism when mood symptoms are part of the autism presentation itself.

Guideline-Recommended Approaches for Behavioral Symptoms in Autism

Current evidence-based guidelines from the American Academy of Child and Adolescent Psychiatry recommend targeting specific symptoms rather than using mood stabilizers like lamotrigine: 2

For Irritability and Aggression

• Risperidone (0.5-3.5 mg/day) or Aripiprazole (5-15 mg/day) are FDA-approved first-line treatments for irritability in autism 2
• Both medications show significant improvement on validated irritability scales compared to placebo 2
• Combining medication with parent training provides superior outcomes compared to medication alone 2

For Hyperactivity and Mood Lability

• Methylphenidate demonstrates efficacy in 49% of autistic children versus 15.5% on placebo for hyperactivity symptoms 2
• Starting dose is 0.3-0.6 mg/kg/dose, 2-3 times daily 2

For Mood Disorders Comorbid with Autism

When an autistic patient has a separate, diagnosed mood disorder (such as bipolar disorder), treatment follows standard mood disorder guidelines rather than autism-specific protocols. 3 In this scenario:

• Lithium or valproate remain first-line mood stabilizers, with the same monitoring requirements as in non-autistic populations 3, 4
• Lamotrigine is approved for maintenance therapy in bipolar disorder and may be considered in this specific context 4
• However, the decision is based on the comorbid mood disorder diagnosis, not the autism itself 3

Limited Supporting Evidence and Important Caveats

One older observational study from 1994 reported improved autistic symptoms in 8 of 13 autistic children treated with lamotrigine for epilepsy, suggesting a "specific positive psychotropic effect." 5 However, this finding:

• Lacks the rigor of the subsequent randomized controlled trial 1
• Occurred in children with epilepsy, not primary behavioral concerns 5
• Has not been replicated in controlled studies 1

A 2012 review listed lamotrigine among anticonvulsants "found to be effective in improving behavioral symptoms of ASD," but provided no specific evidence for this claim and contradicts the negative RCT. 6

Psychiatric Side Effects to Consider

Lamotrigine carries risks of psychiatric adverse effects that are particularly concerning in autistic populations: 7

• Affective switches (mood destabilization) 7
• Acute psychotic episodes 7
• Hallucinations 7

These risks further argue against its use when no proven benefit exists for autism-related mood symptoms.

Clinical Algorithm for Mood Symptoms in Autism

Step 1: Determine if mood symptoms are part of autism presentation or represent a separate comorbid mood disorder 3, 2

Step 2: If symptoms are autism-related irritability/aggression without a separate mood disorder diagnosis:

• Start Risperidone or Aripiprazole as first-line treatment 2
• Implement behavioral interventions and parent training concurrently 2
• Avoid lamotrigine given lack of efficacy 1

Step 3: If a separate bipolar disorder or other mood disorder is diagnosed:

• Follow standard mood disorder treatment guidelines 3, 4
• Consider lithium, valproate, or atypical antipsychotics as first-line agents 4
• Lamotrigine may be considered for maintenance therapy in bipolar disorder specifically 4

Step 4: Monitor treatment response using standardized rating scales (Aberrant Behavior Checklist, Clinical Global Impressions) 2, 1

Common Pitfalls to Avoid

• Do not use lamotrigine based solely on anecdotal reports or older observational data when a negative RCT exists 1, 5
• Do not assume mood lability in autism requires mood stabilizers; it often responds better to antipsychotics targeting irritability 2
• Do not overlook environmental triggers and behavioral interventions, which are essential components of treatment 2
• Do not prescribe mood stabilizers without a clear psychiatric diagnosis beyond autism itself 3, 2