Drowsiness with Higher Doses of Keppra (Levetiracetam)
Yes, Keppra (levetiracetam) can cause significant drowsiness at higher doses, with somnolence being one of the most common dose-dependent side effects reported in clinical studies.
Evidence for Drowsiness with Levetiracetam
The FDA drug label for levetiracetam explicitly lists somnolence as one of the primary adverse effects in cases of overdose 1. This drowsiness effect becomes more pronounced at higher doses:
- Clinical studies show that somnolence and asthenia (weakness) increase in both frequency and severity with increasing doses of levetiracetam 2
- At doses of 4000 mg per day, somnolence becomes more common, suggesting this may be the upper limit for some patients, though individual susceptibility varies 2
Dose-Response Relationship
The drowsiness effect of levetiracetam demonstrates a clear dose-response relationship:
- In dose-escalation studies, somnolence was among the most commonly reported adverse effects, with frequency increasing at higher doses 3
- In overdose cases, profound sedation and respiratory depression have been observed at concentrations 10-40 times higher than therapeutic levels 4
Clinical Implications
When prescribing levetiracetam, especially at higher doses, clinicians should:
- Warn patients about potential drowsiness and advise against driving or operating machinery until they know how the medication affects them 1
- Consider that individual susceptibility to somnolence varies significantly between patients 2
- Be aware that drowsiness may be more pronounced during initial titration and may improve with continued use
- Monitor for signs of excessive sedation, particularly when increasing the dose
Comparison with Other Medications
Unlike some other anticonvulsants, levetiracetam does not have significant interactions with other medications through liver cytochrome P450 pathways 1, which makes it a favorable option for many patients despite the potential for drowsiness.
Management of Drowsiness
If drowsiness becomes problematic:
- Consider administering a larger portion of the daily dose at bedtime
- Evaluate whether a lower dose might still provide adequate seizure control
- Assess for other contributing factors (other medications, sleep disorders)
- Do not abruptly discontinue levetiracetam as this may precipitate seizures
In severe cases of overdose with excessive drowsiness, supportive care is the primary management approach, as there is no specific antidote for levetiracetam overdose 1.