What is the best anticonvulsant to initiate in a patient with seizure disorder?

From the Guidelines

Levetiracetam is the best anticonvulsant to start on a patient due to its broad-spectrum efficacy, favorable safety profile, and minimal drug interactions. This recommendation is based on the most recent and highest quality study, which suggests that levetiracetam, fosphenytoin, or valproate may be used with similar efficacy as second-line agents for seizures refractory to benzodiazepines 1. The choice of anticonvulsant should be individualized based on seizure type, patient age, gender, comorbidities, potential side effects, and drug interactions.

• For many patients, levetiracetam is initiated at 500 mg twice daily and can be titrated up to 1500-3000 mg daily in divided doses based on response and tolerability.
• The use of levetiracetam, fosphenytoin, or valproate will result in cessation of seizures in approximately half of all patients with benzodiazepine-resistant status epilepticus, with the benefit of early treatment being a reduction in morbidity and mortality 1.
• Starting at a low dose and gradually increasing helps minimize adverse effects while establishing seizure control.
• It's essential to consider the patient's specific seizure type, age, and comorbidities when selecting an anticonvulsant, as well as potential side effects and drug interactions.

From the FDA Drug Label

The primary measure of effectiveness was a between group comparison of the percent reduction in weekly partial seizure frequency relative to placebo over the entire randomized treatment period (titration + evaluation period). The percentage of patients (y-axis) who achieved ≥50% reduction in weekly seizure rates from baseline in partial onset seizure frequency over the entire randomized treatment period (titration + evaluation period) within the three treatment groups (x-axis) is presented in Figure 1 Figure 1: Responder Rate (#50% Reduction From Baseline) in Study 1 * statistically significant versus placebo The comparison of levetiracetam 2000 mg/day to levetiracetam 1000 mg/day for responder rate was statistically significant (P=0. 02). The best anticonvulsant to start on a patient is not explicitly stated in the provided drug labels.

• Levetiracetam has been shown to be effective in reducing partial onset seizure frequency, with a statistically significant reduction in seizure frequency compared to placebo 2, 2.
• Valproate has also been shown to be effective in reducing complex partial seizure rates, with a statistically significant reduction in seizure frequency compared to placebo 3. However, there is no direct comparison between levetiracetam and valproate in the provided drug labels, and therefore no conclusion can be drawn about which one is better to start on a patient.

From the Research

Best Anticonvulsant to Start on a Patient

• The choice of anticonvulsant depends on the type of seizure and patient characteristics 4, 5, 6, 7.
• For focal onset seizures, lamotrigine and levetiracetam are suitable first-line treatments, with lamotrigine performing better than most other treatments in terms of treatment failure and seizure control 4, 6.
• For generalized onset seizures, sodium valproate is the first-line treatment, but lamotrigine and levetiracetam can be suitable alternatives, particularly for women of childbearing potential due to valproate's teratogenicity 4, 5, 6, 7.
• Other anticonvulsants like carbamazepine, phenytoin, and topiramate may also be effective, but their efficacy and safety profiles vary 4, 5, 6, 7.

Factors to Consider

• Efficacy in controlling seizures: lamotrigine, levetiracetam, and sodium valproate are effective for generalized tonic-clonic seizures, while ethosuximide and valproate are effective for absence seizures 7.
• Safety profile: valproate has a higher risk of teratogenicity, while lamotrigine and levetiracetam have a more favorable safety profile 4, 5, 6.
• Patient characteristics: age, sex, and comorbidities can influence the choice of anticonvulsant 4, 5, 6.

Treatment Guidelines

• The National Institute for Health and Care Excellence (NICE) recommends carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalized onset seizures 4, 6.
• The SANAD II trial suggests that lamotrigine is superior to levetiracetam and zonisamide for focal epilepsy, while valproate is superior to levetiracetam for generalized and unclassified epilepsy 5.