What are the considerations for using Levetiracetam (antiepileptic medication) in patients with a history of seizure disorders and tics?

Levetiracetam and Tics: Clinical Considerations

Levetiracetam may be beneficial for treating tics in patients with seizure disorders, as it addresses both conditions simultaneously, though behavioral adverse effects require careful monitoring, particularly in patients with pre-existing psychiatric history.

Evidence for Levetiracetam in Tic Disorders

Levetiracetam has demonstrated efficacy in treating tics in children and adolescents with Tourette syndrome, with all 60 patients in a prospective study showing improvements on standardized tic severity scales, and 43 patients (72%) experiencing improvements in behavior and school performance 1. The study used doses of 1,000-2,000 mg/day after titration from an initial 250 mg/day starting dose 1.

Critical Behavioral Monitoring Requirements

The most significant concern when using levetiracetam in patients with tics is the risk of behavioral adverse effects, which paradoxically represent the primary safety concern despite the drug's potential therapeutic benefit for tics:

• Behavioral adverse effects occur in 12-15% of patients overall, with higher risk in learning disabled individuals, those with prior psychiatric history, and those with symptomatic generalized epilepsy 2
• In the tic disorder study, 3 of 60 patients (5%) discontinued treatment due to exaggeration of preexisting behavioral problems 1
• The FDA label documents that 13.3% of adult patients experienced behavioral symptoms (aggression, agitation, anger, anxiety, hostility, irritability) compared to 6.2% on placebo 3
• In pediatric patients, 37.6% experienced behavioral symptoms compared to 18.6% on placebo, including hostility (11.9% vs 6.2%), nervousness (9.9% vs 2.1%), and depression (3.0% vs 1.0%) 3

Practical Implementation Strategy

For patients with both seizure disorders and tics, implement the following approach:

Dosing Protocol

• Start with 250 mg/day and titrate over 3 weeks to 1,000-2,000 mg/day for tic control 1
• For seizure control as adjunctive therapy, standard dosing is 1,000-3,000 mg/day 4, 5
• The 1,000-2,000 mg/day range may provide dual benefit for both seizures and tics 1

Monitoring Requirements

• Assess behavioral symptoms at every visit during the first 4 weeks, as most behavioral adverse effects occur within this timeframe 3
• Specifically monitor for: aggression, agitation, anger, anxiety, hostility, irritability, mood changes, and depression 3
• Evaluate tic severity using standardized scales (Yale Global Tic Severity Scale) 1
• Monitor seizure frequency and control 3

Risk Stratification

Patients at highest risk for behavioral adverse effects include:

• Those with learning disabilities 2
• Prior psychiatric history 2
• Symptomatic generalized epilepsy 2
• Pediatric patients (37.6% behavioral symptom rate) 3

For high-risk patients, consider more frequent monitoring (weekly for first month) and lower starting doses with slower titration.

Advantages Over Alternative Antiepileptic Drugs

Levetiracetam offers several advantages for patients with seizures and tics:

• No cytochrome P450 interactions, eliminating concerns about drug-drug interactions 5, 6
• No cognitive impairment or weight gain 5
• Rapid and complete absorption with high bioavailability 5
• Established efficacy for multiple seizure types including partial onset, myoclonic, and generalized tonic-clonic seizures 4, 5
• Potential therapeutic benefit for tics themselves, unlike traditional antiepileptic drugs 1

When to Discontinue or Adjust

Discontinue levetiracetam if:

• Severe behavioral deterioration occurs (psychosis, severe aggression, suicidal ideation) 3
• Behavioral symptoms significantly impair function despite dose reduction 1

Consider dose reduction if:

• Mild to moderate behavioral symptoms emerge 3
• Somnolence or asthenia interferes with daily activities 3

If discontinuation is necessary, taper by 500 mg increments every 1-2 weeks to minimize seizure recurrence risk 7.

Alternative Considerations

If levetiracetam causes intolerable behavioral effects, alternative antiepileptic drugs for seizure control include valproate (88% efficacy, 0% hypotension risk) or phenytoin/fosphenytoin (84% efficacy) 4, though these lack the potential tic-suppressing benefit. Separate tic management would then require traditional tic-suppressing medications (alpha-2 agonists, antipsychotics), which carry their own adverse effect profiles.