What adjustments should be made to the treatment regimen for a patient with nocturnal seizures and a catamenial pattern, currently on Keppra (levetiracetam) 500mg once daily before bed?

Treatment Adjustment for Nocturnal Catamenial Seizures on Subtherapeutic Keppra

The current dose of 500mg once daily is inadequate and should be increased to 500mg twice daily (1000mg total daily dose), as this patient has experienced breakthrough seizures on the current regimen and standard therapeutic dosing for levetiracetam in adults ranges from 1000-3000mg daily in divided doses. 1

Immediate Dose Optimization

Increase levetiracetam to 500mg twice daily (morning and evening) rather than once daily dosing. The current once-daily regimen provides subtherapeutic coverage, particularly during daytime hours when the drug level drops. 1

• Standard adult dosing for partial onset seizures begins at 1000mg daily (500mg twice daily) and can be titrated up to 3000mg daily based on response 1
• The patient's breakthrough seizure after only a few weeks indicates the 500mg once-daily dose is insufficient
• Levetiracetam has a half-life of approximately 6-8 hours in adults, making twice-daily dosing pharmacologically appropriate 1

Addressing the Catamenial Pattern

Add intermittent pulse dosing during the premenstrual week (approximately 7 days before and during menstruation) by increasing to 1000mg twice daily during this high-risk period. 2

• A study of five women with catamenial epilepsy showed effective seizure control using intermittent levetiracetam 500mg twice daily (67% of patients) or 750mg twice daily (33% of patients) administered 1 week prior to and during menstruation 2
• This pulsed approach targets the perimenstrual (C1) pattern, which accounts for seizure exacerbation in approximately one-third of women with catamenial epilepsy 3, 4
• The hormonal mechanism involves premenstrual progesterone withdrawal, which reduces GABAergic inhibition and increases seizure susceptibility 3, 4

Evaluating the Sleepwalking Episode

Investigate whether the apparent sleepwalking represents a nocturnal seizure manifestation rather than a parasomnia. 5

• The temporal relationship between starting antiepileptic medication and new sleepwalking behavior raises concern for nocturnal seizure activity
• Nocturnal complex seizures can mimic sleepwalking and other parasomnias 5
• Consider polysomnography with extended EEG monitoring if episodes continue, as this can differentiate REM behavior disorder, non-REM parasomnias, and nocturnal seizures 5

Specific Treatment Algorithm

1. Week 1-2: Increase baseline dose to 500mg twice daily (8 AM and 8 PM) 1

2. Week 3 onward: Maintain 500mg twice daily as baseline, but increase to 1000mg twice daily starting 7 days before expected menstruation through the end of menses 2

3. Monitor response: Track seizure frequency using a seizure diary that documents timing relative to menstrual cycle 3, 4

4. If seizures persist after 3 months: Consider increasing baseline dose to 750mg twice daily (1500mg total daily), with pulse dosing to 1500mg twice daily during the perimenstrual period 1, 2

Critical Monitoring Considerations

Monitor for neuropsychiatric adverse effects, particularly behavioral changes, mood disturbances, and suicidal ideation. 1

• Levetiracetam increases risk of suicidal thoughts and behavior, with 3.4 events per 1000 patients in epilepsy trials versus 1.0 per 1000 in placebo groups 1
• Behavioral abnormalities (aggression, agitation, depression, irritability) occur in 13.3% of levetiracetam patients versus 6.2% on placebo 1
• Somnolence affects 14.8% of adult patients on levetiracetam versus 8.4% on placebo, though this may actually benefit nocturnal seizure control 1

Assess renal function before dose escalation. 1

• Levetiracetam is primarily renally excreted, and dose adjustment is required if creatinine clearance is impaired 1
• No hepatic dose adjustment is needed 1

Alternative Considerations if Levetiracetam Fails

If seizures remain uncontrolled after optimizing levetiracetam dosing for 3 months, consider adding or switching to valproate or lamotrigine. 6, 7

• Valproate 20-30mg/kg/day shows 88% efficacy for seizure control with minimal hypotension risk 6
• Lamotrigine demonstrated efficacy in 66% of women with catamenial epilepsy in one prospective study, with the added benefit of potentially increasing progesterone levels 7
• Hormonal treatments (progesterone, norethisterone) have shown conflicting evidence and should be considered only after optimizing antiepileptic medication 3

Common Pitfalls to Avoid

Do not use once-daily dosing for levetiracetam in active epilepsy. The short half-life necessitates twice-daily administration for consistent therapeutic levels. 1

Do not assume the sleepwalking is benign without further evaluation. Nocturnal seizures can present as complex behaviors that mimic parasomnias, and misdiagnosis could lead to inadequate seizure control. 5

Do not delay dose optimization while waiting to confirm the catamenial pattern. The patient has already demonstrated breakthrough seizures on the current regimen, indicating immediate need for dose increase regardless of menstrual timing. 1