Is triple therapy with lacosamide (Lacosamide), levetiracetam (Levetiracetam), and phenytoin (Phenytoin) necessary for a patient with a history of convulsions?

From the Guidelines

The patient's current regimen of three antiepileptic drugs (lacosamide 200 mg, levetiracetam 1500 mg, and phenytoin 100 mg) may not be necessary and should be optimized to minimize adverse effects and improve quality of life. According to the most recent study 1, the use of levetiracetam, fosphenytoin, or valproate can result in cessation of seizures in approximately half of all patients with benzodiazepine-resistant status epilepticus. Considering the potential benefits and harms of each medication, I recommend gradually transitioning to a two-drug regimen by first tapering phenytoin while optimizing the doses of lacosamide and levetiracetam.

Rationale for Medication Optimization

• Phenytoin has the most complex pharmacokinetics, numerous drug interactions, and long-term side effects among these medications 1.
• Lacosamide and levetiracetam have a more favorable safety profile and can be effective in controlling seizures.
• The optimal approach would be to increase lacosamide to 300-400 mg daily (divided twice daily) and maintain levetiracetam at 1500 mg daily (or increase to 2000 mg if needed), while slowly withdrawing phenytoin over 4-6 weeks with regular monitoring for breakthrough seizures.

Monitoring and Follow-up

• Regular follow-up appointments every 4-6 weeks are essential to monitor seizure control, medication levels (particularly during phenytoin withdrawal), and side effects.
• The patient should maintain a seizure diary and be educated about seizure precautions, including avoiding driving during medication changes.
• If seizures remain controlled for 6-12 months on the two-drug regimen, further reduction to monotherapy could be considered.

Considerations for Special Populations

• Patients with a history of seizures or CNS disease may require anti-seizure prophylaxis with levetiracetam, as recommended in the study 1.
• However, this patient's specific situation does not indicate a need for anti-seizure prophylaxis, and the focus should be on optimizing their current medication regimen.

From the Research

Medication Necessity

• The patient is currently taking lacosamide 200 mg, levetiracetam 1500 mg, and phenytoin 100 mg for convulsions 2.
• According to the study on antiepileptic drugs, levetiracetam is often used as first-line therapy due to its efficacy and favorable side effect profile 3, 2.
• Lacosamide has been used for refractory seizures and may offer similar seizure control without the negative aspects of traditional agents like phenytoin 2.
• Phenytoin is an older antiepileptic drug with tolerability and pharmacokinetic disadvantages, and its use may result in adverse effects such as decreased systolic blood pressure 2.

Plan of Care

• The ultimate goal of seizure management is for the patient to have no seizures and no considerable adverse effects from the treatment 4.
• A rational approach to antiepileptic drug therapy involves selecting medications based on the patient's epilepsy, comorbidities, and potential for adverse events 3.
• The patient's current medication regimen should be evaluated to determine if all three medications are necessary, considering the potential for seizure freedom and adverse effects 4, 3, 2.
• If the patient has failed to achieve seizure control with the current regimen, additional therapy, including dietary, device, or surgical treatments, may need to be considered 4.