What is the first-line therapy for seizure prophylaxis in the elderly when Lamotrigine (lamotrigine) cannot be used?

From the Guidelines

Levetiracetam is the recommended first-line therapy for seizure prophylaxis in elderly patients when lamotrigine cannot be used. The typical starting dose is 500 mg twice daily, which can be gradually increased to 1000-1500 mg twice daily based on clinical response and tolerability 1. Levetiracetam is preferred in the elderly due to its favorable pharmacokinetic profile, minimal drug interactions, and lack of significant hepatic metabolism. It does not require blood level monitoring and has a relatively low side effect profile compared to older antiepileptic drugs. Common side effects include somnolence, dizziness, and potential behavioral changes, which should be monitored closely in elderly patients. Dose adjustment is necessary in patients with renal impairment, which is common in the elderly population. Alternative options include oxcarbazepine or lacosamide if levetiracetam is not tolerated, though these may require more careful titration and monitoring. The medication should be taken consistently at the same times each day, and patients should be counseled not to discontinue therapy abruptly as this could precipitate seizures.

Some key points to consider when using levetiracetam for seizure prophylaxis in elderly patients include:

• Minimal drug interactions, making it a good option for patients with multiple comorbidities
• Lack of significant hepatic metabolism, reducing the risk of drug interactions and adverse effects
• Relatively low side effect profile, with common side effects including somnolence, dizziness, and potential behavioral changes
• Dose adjustment necessary in patients with renal impairment, which is common in the elderly population
• Alternative options available if levetiracetam is not tolerated, including oxcarbazepine or lacosamide

It's also important to note that current guidelines suggest that anti-seizure medications should not be used as primary prophylaxis among patients with brain metastases, unless there is a high risk of seizures or a history of seizures 1. However, in the context of seizure prophylaxis in elderly patients when lamotrigine cannot be used, levetiracetam is a suitable alternative.

In terms of the evidence, a study published in 2022 found that levetiracetam, lacosamide, or lamotrigine are generally preferred due to their minimal impact on hepatic metabolizing enzymes 1. Another study published in 2014 found that levetiracetam was effective in stopping seizures in patients with status epilepticus refractory to benzodiazepines and phenytoin 1. Overall, the evidence suggests that levetiracetam is a safe and effective option for seizure prophylaxis in elderly patients when lamotrigine cannot be used.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

First-Line Therapy for Seizure Prophylaxis in Elderly When Lamotrigine Can't Be Used

• The study 2 compared the clinical effectiveness and cost-effectiveness of lamotrigine with levetiracetam and zonisamide for focal epilepsy, and valproate with levetiracetam for generalized and unclassified epilepsy.
• The results showed that levetiracetam did not meet the criteria for non-inferiority in the primary intention-to-treat analysis of time to 12-month remission, but zonisamide did meet the criteria.
• Another study 3 compared the time to withdrawal of allocated treatment, remission, and first seizure of 10 antiepileptic drugs, including levetiracetam, lamotrigine, and valproate.
• The network meta-analysis showed that levetiracetam performed significantly better than carbamazepine and lamotrigine for individuals with partial seizures, and sodium valproate performed significantly better than carbamazepine, topiramate, and phenobarbitone for individuals with generalized onset seizures.
• A systematic review and meta-analysis 4 evaluated the efficacy of levetiracetam for seizure prophylaxis in patients with intracerebral hemorrhage, traumatic brain injury, supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage.
• The results did not demonstrate significant reductions in seizure incidence, but levetiracetam may be preferred post supratentorial neurosurgery.
• A descriptive analysis 5 assessed the efficacy of levetiracetam as first-line therapy in women with idiopathic generalized epilepsy, and found that levetiracetam could be an effective drug as first-line treatment, but adverse effects are its main limitation.
• A systematic review and network meta-analyses 6 compared the relative efficacy of antiepileptic drugs in the monotherapy treatment of generalized epileptic seizures, and found that lamotrigine, levetiracetam, and topiramate are as effective as valproate for treating generalized tonic-clonic, tonic, and clonic seizures.

Alternative Options to Lamotrigine

• Levetiracetam may be a suitable alternative to lamotrigine for seizure prophylaxis in elderly patients, based on the results of the studies 2, 3, and 5.
• Valproate may also be considered as an alternative, but its use may be limited due to its teratogenicity, especially in women of childbearing potential 3 and 6.
• Other antiepileptic drugs, such as zonisamide and topiramate, may also be considered as alternative options, but more research is needed to determine their efficacy and safety in elderly patients 2 and 6.