Can lacosamide or Keppra (levetiracetam) cause encephalopathy?

From the Guidelines

Both lacosamide and levetiracetam (Keppra) can potentially cause encephalopathy, though it is considered a rare adverse effect. Encephalopathy from these medications typically presents as confusion, altered mental status, somnolence, or behavioral changes. Levetiracetam is more commonly associated with behavioral side effects including irritability, aggression, and mood changes, while lacosamide may cause dizziness, headache, and coordination difficulties that can mimic mild encephalopathy. The risk increases with higher doses, rapid dose escalation, renal impairment (especially for levetiracetam which is renally cleared), and in elderly patients. Drug-induced encephalopathy is usually reversible with dose reduction or discontinuation of the medication. Patients with underlying neurological conditions may be more susceptible to these effects. If a patient develops new cognitive symptoms while taking either medication, healthcare providers should evaluate for drug-induced encephalopathy, especially if symptoms appeared after starting the medication or increasing the dose.

Key Points to Consider

• The risk of encephalopathy is higher with higher doses and rapid dose escalation of lacosamide and levetiracetam.
• Renal impairment, especially with levetiracetam, can increase the risk of encephalopathy due to decreased drug clearance.
• Elderly patients are more susceptible to the adverse effects of these medications, including encephalopathy.
• Patients with underlying neurological conditions should be closely monitored for signs of encephalopathy when taking lacosamide or levetiracetam.
• The most recent and highest quality study, 1, provides evidence on the effects of antiseizure medications, including lacosamide and levetiracetam, on motor vehicle driving performance, which can be related to encephalopathy.

Recommendations for Healthcare Providers

• Monitor patients closely for signs of encephalopathy, especially when starting or increasing the dose of lacosamide or levetiracetam.
• Consider alternative medications or dose adjustments for patients at high risk of encephalopathy.
• Educate patients and their families about the potential risks of encephalopathy and the importance of reporting any new cognitive symptoms.
• Refer to the most recent and highest quality studies, such as 1, for guidance on the management of patients taking lacosamide or levetiracetam.

From the Research

Lacosamide and Encephalopathy

• There is no direct evidence in the provided studies that lacosamide causes encephalopathy 2, 3, 4, 5, 6.
• The studies focus on the efficacy and safety of lacosamide as an add-on therapy for drug-resistant focal epilepsy, its comparison with other antiepileptic drugs, and its effects on cognitive function and psychiatric profiles in patients with epilepsy.

Keppra (Levetiracetam) and Encephalopathy

• None of the provided studies directly investigate the relationship between Keppra (levetiracetam) and encephalopathy 2, 3, 4, 5, 6.
• However, one study mentions levetiracetam as a non-enzyme inducer, which may have a less negative influence on bone mineral density compared to enzyme inducers 3.

Adverse Events Associated with Lacosamide

• The studies report various adverse events associated with lacosamide, including abnormal coordination, blurred vision, diplopia, dizziness, nausea, somnolence, vomiting, and others 2, 4, 5.
• However, encephalopathy is not mentioned as an adverse event in any of the provided studies.