What is the best medication to add to levetiracetam (Keppra) for a 68-year-old man with focal motor epilepsy, hypertension, and a history of stroke, who is currently experiencing 2-3 seizures per week despite taking the maximum tolerated dose of levetiracetam?

Management of Focal Motor Epilepsy in an Elderly Patient with Persistent Seizures

Adding brivaracetam is the best option for this 68-year-old man with focal motor epilepsy who continues to experience 2-3 seizures per week despite maximum tolerated doses of levetiracetam.

Rationale for Adding Brivaracetam

Brivaracetam is the optimal choice for several reasons:

1. Efficacy in Levetiracetam-Resistant Patients:

   • While levetiracetam is an effective first-line agent for focal epilepsy, this patient is experiencing breakthrough seizures despite maximum tolerated doses.
   • Brivaracetam has shown efficacy in patients who previously failed levetiracetam treatment, with 46.2% of levetiracetam non-responders achieving positive response to brivaracetam 1.

2. Mechanism of Action:

   • Brivaracetam has a similar but more selective binding profile to synaptic vesicle protein 2A compared to levetiracetam, potentially providing additional seizure control 2.

3. Patient-Specific Considerations:

   • The patient has a history of stroke and hypertension, making medication interactions and cardiovascular side effects important considerations.
   • Brivaracetam has minimal drug interactions with the patient's current medications (atorvastatin, aspirin, lisinopril, and hydrochlorothiazide).
   • The patient prefers a simple regimen, and brivaracetam can be added without complex titration.

Why Other Options Are Less Optimal

1. Phenytoin:

   • Higher risk of adverse effects including hypotension and cardiac arrhythmias 3.
   • Significant enzyme inducer causing multiple drug interactions with other medications 3.
   • Less favorable side effect profile compared to newer antiepileptic drugs.

2. Lamotrigine:

   • Requires slow titration (over 6-8 weeks) to avoid serious rash, which doesn't address the immediate need for seizure control.
   • Not ideal for a patient who prefers a simple regimen due to complex titration schedule.

3. Zonisamide:

   • Less evidence supporting its use as add-on therapy specifically with levetiracetam.
   • Higher risk of cognitive side effects in elderly patients.

Dosing and Administration of Brivaracetam

• Start brivaracetam at 50 mg twice daily.
• Can be increased to 100 mg twice daily if needed for better seizure control.
• No titration period is required, allowing for immediate full therapeutic dosing 2.
• Continue levetiracetam at the current maximum tolerated dose initially.

Monitoring and Follow-up

1. Efficacy Assessment:

   • Monitor seizure frequency with patient seizure diary.
   • Assess for 50% or greater reduction in seizure frequency (the standard measure of response).
   • Consider EEG monitoring if clinical response is unclear.

2. Side Effect Monitoring:

   • Watch for somnolence, which is the most common adverse effect with this class of medications 4.
   • Monitor for behavioral changes, though these are less common with brivaracetam than levetiracetam 1.
   • Assess for any changes in cognition, particularly important in this elderly patient with history of stroke.

Important Considerations and Potential Pitfalls

1. Levetiracetam Interaction:

   • FDA labeling notes that brivaracetam provided "no added benefit when co-administered with levetiracetam" in clinical trials 2.
   • However, real-world data shows that 46.2% of levetiracetam non-responders did have positive response to brivaracetam 1.
   • Consider eventual transition from levetiracetam to brivaracetam monotherapy if good response is achieved.

2. Elderly-Specific Concerns:

   • Start at the lower end of the dosing range and monitor closely for side effects.
   • Be vigilant for drug interactions with the patient's cardiovascular medications.
   • Consider renal function when dosing, as both levetiracetam and brivaracetam are primarily renally excreted.

3. Behavioral Side Effects:

   • While behavioral side effects are less common with brivaracetam than levetiracetam (22.4% vs 55.1%), they can still occur 1.
   • Newly found behavioral side effects after switching from levetiracetam to brivaracetam occur in approximately 7.1% of patients 1.

By adding brivaracetam to this patient's regimen, we can potentially achieve better seizure control while maintaining a simple medication regimen and minimizing the risk of adverse effects in this elderly patient with comorbidities.