What is the best selective serotonin reuptake inhibitor (SSRI) to use with Keppra (levetiracetam) in a patient with a seizure disorder?

Best SSRI with Levetiracetam (Keppra) in Seizure Disorder

Citalopram or escitalopram are the preferred SSRIs for patients on levetiracetam with seizure disorder due to their minimal impact on seizure threshold and favorable drug interaction profile.

Considerations When Selecting an SSRI for Patients with Seizure Disorder

General Considerations

• All SSRIs have been associated with seizures, but the risk is relatively low
• SSRIs should be used cautiously in patients with a history of seizure disorder 1
• Careful monitoring is required, especially during initiation and dose adjustments

Drug-Specific Considerations

Preferred Options:

1. Citalopram/Escitalopram

   • Minimal impact on seizure threshold 1
   • Low potential for drug-drug interactions
   • No significant pharmacokinetic interactions with levetiracetam
   • Demonstrated safety in clinical studies 1

2. Sertraline

   • Generally safe in epilepsy patients with only 6% experiencing increased seizure frequency in clinical studies 2
   • Most patients who experienced increased seizures could be managed with AED dose adjustments
   • Lower doses may be associated with seizure exacerbation (paradoxically)

Less Preferred Options:

1. Fluvoxamine

   • Greater potential for drug-drug interactions 1
   • May complicate management of seizure medications

2. Paroxetine

   • Associated with discontinuation syndrome 1
   • Higher risk of suicidal thinking compared to other SSRIs 1

3. Fluoxetine

   • Longer half-life may complicate management if adverse effects occur

Levetiracetam (Keppra) Considerations

• Levetiracetam is effective for partial-onset seizures and other seizure types 3
• Well-tolerated with minimal drug interactions due to:
  • Minimal metabolism (hydrolysis of acetamide group)
  • Primarily renal elimination
  • Lack of cytochrome P450 enzyme induction 3
• Common side effects include somnolence and asthenia 4, 5
• Behavioral adverse effects may occur in some patients 3

Implementation Strategy

Initiation and Titration

1. Start with low doses of the selected SSRI
2. Increase dose slowly while monitoring for seizure activity
3. Monitor closely in the first 24-48 hours after dosage changes 1

Monitoring

1. Watch for signs of serotonin syndrome, especially if combining with other serotonergic medications
2. Monitor for behavioral activation/agitation, especially early in treatment
3. Assess for suicidal ideation, particularly in the first months of treatment 1

Special Considerations

Potential Pitfalls

• Avoid combining SSRIs with MAOIs due to risk of serotonin syndrome 1
• Be cautious with citalopram doses exceeding 40mg/day due to QT prolongation risk 1
• Consider that behavioral side effects of SSRIs may overlap with or exacerbate behavioral effects sometimes seen with levetiracetam 3

Seizure Exacerbation Management

If seizures worsen after SSRI initiation:

1. Consider adjusting antiepileptic medication dose before discontinuing the SSRI 2
2. Evaluate for other potential causes of seizure exacerbation
3. If necessary, switch to an alternative SSRI with lower seizure risk

Conclusion

When selecting an SSRI for patients on levetiracetam with seizure disorder, citalopram/escitalopram should be the first choice due to their favorable safety profile and minimal interaction with seizure threshold. Sertraline represents a reasonable alternative with demonstrated safety in epilepsy patients. Start with low doses, titrate slowly, and monitor closely for seizure activity and behavioral changes.