Can Keppra (levetiracetam) cause aggressive behavior in individuals with autism?

Levetiracetam Can Cause Aggressive Behavior in Individuals with Autism

Yes, Keppra (levetiracetam) can cause aggressive behavior in individuals with autism, and this is documented in both FDA labeling and clinical guidelines.

Evidence for Levetiracetam-Induced Aggression

According to the FDA drug label for levetiracetam, behavioral abnormalities including aggression are well-documented adverse effects 1:

• In pediatric patients, 37.6% of levetiracetam-treated patients experienced behavioral symptoms compared to 18.6% of placebo patients
• Hostility was specifically reported in 11.9% of levetiracetam-treated patients versus 6.2% of placebo patients
• Non-psychotic behavioral disorders (including aggression) occurred in 11.4% of levetiracetam-treated patients compared to 3.6% of placebo patients in trials for primary generalized tonic-clonic seizures

The American Academy of Child and Adolescent Psychiatry practice guidelines specifically note that in a study of levetiracetam in children with autism, "aggression" was reported as a significant side effect 2.

Mechanism and Risk Factors

The exact mechanism by which levetiracetam causes behavioral changes is not fully understood, but several patterns emerge from the evidence:

• Behavioral side effects appear more common in:
  • Pediatric populations
  • Patients with pre-existing neuropsychiatric conditions (including autism)
  • Patients with intellectual disability

A study by Wasserman et al. (2006) specifically identified aggression as a significant side effect of levetiracetam in children with autism 2.

Clinical Management Algorithm

When considering levetiracetam in patients with autism:

1. Risk assessment before starting:

   • Document baseline behavioral functioning
   • Consider alternative anticonvulsants if the patient already has behavioral issues
   • Inform caregivers about potential behavioral side effects

2. Monitoring during treatment:

   • Regularly assess for new or worsening aggressive behaviors
   • Use standardized rating scales when possible (e.g., Aberrant Behavior Checklist)
   • Schedule more frequent follow-ups during the first 4 weeks (when most behavioral effects emerge)

3. If aggression develops:

   • Consider dose reduction (behavioral effects may be dose-dependent)
   • If severe or persistent, consider medication discontinuation
   • Transition to an alternative anticonvulsant with lower risk of behavioral effects

Alternative Anticonvulsants

If a patient with autism requires seizure management but develops aggression on levetiracetam, consider these alternatives with potentially lower behavioral impact:

• Valproic acid (though it has its own side effect profile)
• Lamotrigine (though slower titration is required)
• Carbamazepine (though drug interactions must be monitored)

Important Caveats

• Individual variability: Not all patients with autism will develop aggressive behavior on levetiracetam
• Risk-benefit assessment: In some cases, the seizure control benefits may outweigh behavioral risks
• Reversibility: Behavioral effects are typically reversible upon discontinuation, as demonstrated in case reports of autistic regression that resolved after stopping levetiracetam 3
• Paradoxical effects: Some anticonvulsants that cause aggression in some patients may actually improve behavior in others, highlighting the need for individualized assessment

Conclusion

When prescribing levetiracetam to individuals with autism, clinicians should maintain heightened vigilance for behavioral side effects, particularly aggression. The medication should be promptly discontinued or the dose reduced if significant behavioral deterioration occurs, as these effects are typically reversible upon discontinuation.