What is the best antiepileptic drug (AED) for partial seizures?

Best Antiepileptic for Partial Seizures

Levetiracetam is the preferred first-line antiepileptic drug for partial-onset seizures due to superior treatment retention rates, fewer drug interactions, and better tolerability compared to traditional agents. 1

First-Line Monotherapy Recommendations

The American Academy of Neurology recommends three drugs as first-line monotherapy for partial-onset seizures: levetiracetam, carbamazepine, or lamotrigine. 1 However, the evidence clearly favors levetiracetam as the optimal initial choice:

• Levetiracetam demonstrates superior treatment retention compared to traditional first-line agents, making it the most practical choice for long-term seizure control. 1
• Levetiracetam can be administered as 1,500 mg oral load or rapid IV loading at doses up to 60 mg/kg, with minimal adverse effects (fatigue, dizziness, rarely pain at infusion site). 2, 3
• The main concern with levetiracetam is psychiatric side effects in some patients, which requires monitoring but does not outweigh its overall advantages. 1

Alternative First-Line Options

If levetiracetam is not tolerated or contraindicated:

• Carbamazepine remains the preferred traditional first-line alternative, particularly recommended by the American Academy of Neurology. 1, 3

• Carbamazepine is administered as 8 mg/kg oral suspension for loading doses, with common side effects including drowsiness, nausea, and dizziness. 2, 1

• Carbamazepine showed similar efficacy to lamotrigine in head-to-head trials but has more drug interactions due to enzyme induction. 4

• Lamotrigine performs significantly better than gabapentin and phenobarbitone for treatment retention and is particularly suitable for women of childbearing potential due to lower teratogenicity risk compared to valproate. 1

• Lamotrigine can be loaded at 6.5 mg/kg single oral dose only if the patient was previously on lamotrigine for >6 months without rash history and only off for <5 days. 2

• In direct comparison trials, lamotrigine showed significantly better treatment withdrawal rates than carbamazepine (HR 0.72,95% CI 0.63 to 0.82), though carbamazepine had slightly better seizure control for time to first seizure. 4

Drugs to Avoid as First-Line

• Do not use phenytoin, phenobarbital, or carbamazepine as first choice due to their side-effect profile and drug interactions, especially with steroids and various cytotoxic and targeted agents. 1
• Phenytoin and phenobarbital are considered last-choice drugs because of their adverse event profiles. 5
• Avoid valproic acid in women of childbearing potential due to significant teratogenicity risks. 1, 3

Second-Line and Adjunctive Therapy Options

When monotherapy fails or as add-on therapy:

• Lacosamide is available in both oral and IV formulations with minimal drug-drug interactions as a non-enzyme-inducing antiepileptic drug, initiated at 100 mg/day with weekly titration in 100 mg/day increments to target dose of 200-400 mg/day. 1, 3
• Topiramate has demonstrated efficacy in controlled trials, with 58% of patients achieving the maximal dose of 400 mg/day for ≥2 weeks in monotherapy trials. 6
• Gabapentin is typically administered as 900 mg/day oral for 3 days, used as an adjunct for partial seizures with side effects including somnolence, dizziness, ataxia, and fatigue. 2, 1

Critical Pitfalls to Avoid

• Do not abruptly discontinue antiepileptic drugs, as this can precipitate withdrawal seizures. 1
• Do not prescribe antiepileptic drugs routinely after a first unprovoked seizure unless there are abnormal EEG and imaging findings or severe social implications. 1
• Do not discontinue treatment too early—consider discontinuation only after 2 seizure-free years, taking into account clinical, social, and personal factors. 1, 3
• Prescribe folic acid routinely when on antiepileptic drugs, and control seizures with monotherapy at minimum effective dose. 1
• For patients with intellectual disability, consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects. 1, 3

Loading Strategies in the Emergency Department

When resuming antiepileptic medication in the ED is deemed appropriate:

• Levetiracetam: 1,500 mg oral load or rapid IV loading up to 60 mg/kg; no seizures occurred within 24 hours of loading in oral loading studies. 2
• Carbamazepine: 8 mg/kg oral suspension as single load (oral tablet has slow/erratic absorption); common adverse effects include drowsiness (26%), nausea (23%), dizziness. 2
• Phenytoin: 20 mg/kg divided in maximum doses of 400 mg every 2 hours orally, or 18 mg/kg IV at maximum rate of 50 mg/min; IV is faster but has more serious adverse effects including hypotension, bradyarrhythmias, cardiac arrest. 2