What is the diagnosis and treatment for a Focal Seizure (partial seizure)?

From the Guidelines

Focal seizures should be treated with antiepileptic medications, such as levetiracetam, as the first-line therapy, with a dose range of 1000-3000 mg/day, as recommended by the most recent clinical policy 1. When managing focal seizures, it is crucial to consider the potential causes and triggers, such as noncompliance with antiseizure drug therapy, prescribed substance use (e.g., tramadol), and illicit substance use (e.g., cocaine), which can lower the seizure threshold 1. Key considerations in treatment include:

• Starting with a single medication at a low dose and gradually increasing until seizures are controlled or side effects occur
• Switching to an alternative monotherapy or adding a second medication if the first medication fails
• Considering surgical options, such as resection of the seizure focus, responsive neurostimulation, or vagus nerve stimulation, for drug-resistant focal seizures
• Avoiding seizure triggers, including sleep deprivation, alcohol, and stress
• Regular follow-up with a neurologist to monitor medication effectiveness and adjust treatment as needed The clinical policy update from 2024 emphasizes the importance of optimal dosing of benzodiazepines as first-line treatment for recurrent seizures, with second-line treatment including agents such as phenytoin, levetiracetam, and valproic acid 1. In the context of focal seizures, levetiracetam is a suitable option, given its efficacy and relatively favorable side effect profile, as supported by the most recent clinical policy 1.

From the FDA Drug Label

Levetiracetam is indicated as adjunctive treatment of partial onset seizures in adults and children 4 years of age and older with epilepsy. Partial Onset Seizures Adults 16 Years And Older In clinical trials, daily doses of 1000 mg, 2000 mg, and 3000 mg, given as twice-daily dosing, were shown to be effective Pediatric Patients Ages 4 To <16 Years Treatment should be initiated with a daily dose of 20 mg/kg in 2 divided doses (10 mg/kg BID).

The recommended dose for focal seizures (also known as partial onset seizures) is:

• For adults 16 years and older: 1000 mg/day to 3000 mg/day, given as twice-daily dosing
• For pediatric patients ages 4 to <16 years: 20 mg/kg/day to 60 mg/kg/day, given as twice-daily dosing 2 Key points:
• The dose should be initiated at 1000 mg/day for adults and 20 mg/kg/day for pediatric patients
• The dose can be increased every 2 weeks by increments of 1000 mg/day for adults and 20 mg/kg/day for pediatric patients
• The maximum recommended daily dose is 3000 mg for adults and 60 mg/kg/day for pediatric patients

From the Research

Focal Seizure Treatment Options

• The study 3 compared the clinical effectiveness and cost-effectiveness of lamotrigine, levetiracetam, and zonisamide for focal epilepsy, and valproate and levetiracetam for generalised 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 4 discussed the neuropharmacology of antiseizure drugs and presented the current state of the literature on the efficacy and tolerability of these agents.
• The study 5 compared the efficacy of unique antiepileptic drug regimens among patients with focal epilepsy and found that lamotrigine monotherapy was more effective than phenytoin monotherapy.
• A network meta-analysis 6 compared the time to withdrawal of allocated treatment, remission, and first seizure of 10 antiepileptic drugs currently used as monotherapy in children and adults with partial onset seizures or generalised onset tonic-clonic seizures.
• The results 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 generalised onset seizures.

Effectiveness of Generic Antiepileptic Drugs

• A retrospective data analysis 7 compared the effectiveness of single-source generic carbamazepine, lamotrigine, or levetiracetam in newly diagnosed focal epilepsy.
• The results showed that at the end of the 24-month study period, the seizure-freedom rate for levetiracetam was superior to carbamazepine and lamotrigine.
• The study also found that the tolerability and retention rates showed no significant difference among the three groups.

Adverse Reactions and Tolerability

• The study 3 reported that adverse reactions were reported by 33% of participants starting lamotrigine, 44% starting levetiracetam, and 45% starting zonisamide.
• The study 6 found that the most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness, and rash or skin disorders.
• The study 7 found that rash was the most common adverse event for carbamazepine and lamotrigine, and mood changes were the most common adverse event for levetiracetam.