What is the treatment for partial seizures?

Treatment of Partial-Onset Seizures

For partial-onset seizures, levetiracetam, carbamazepine, or lamotrigine should be used as first-line monotherapy, with levetiracetam showing superior treatment retention compared to traditional first-line agents. 1, 2

First-Line Monotherapy Options

Preferred Initial Agents

• Levetiracetam is the preferred first-line option at most neuro-oncology centers due to superior treatment retention rates compared to carbamazepine and lamotrigine, with fewer drug interactions and better tolerability, though psychiatric side effects remain a concern in some patients 3, 2

• Carbamazepine is recommended by the American Academy of Neurology as the preferred traditional first-line alternative, typically administered as 8 mg/kg oral suspension for loading doses, with common side effects including drowsiness, nausea, and dizziness 1, 2

• 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, though it requires several weeks of titration to reach therapeutic levels 3, 1, 2

Alternative First-Line Options

• Phenytoin can be administered as 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, with side effects including hypotension, cardiac dysrhythmias, and risk of purple glove syndrome with IV administration 1

• Valproic acid may be administered up to 30 mg/kg IV at maximum rate of 10 mg/kg/min, but should be avoided in women of childbearing potential due to significant teratogenicity risks and long-term impacts on bone health 1, 4

Second-Line and Adjunctive Therapy

When Monotherapy Fails

• 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, 4

• Topiramate has demonstrated effectiveness in adjunctive therapy for partial-onset seizures, with patients receiving active drug beginning at 100 mg per day, increased by 100 mg or 200 mg/day increments weekly or every other week until the assigned dose is reached 5

• Gabapentin is typically administered as 900 mg/day oral for 3 days, with side effects including somnolence, dizziness, ataxia, and fatigue, used as an adjunct for partial seizures 1

• Zonisamide demonstrated statistically significant treatment differences at doses of 100,200, and 400 mg/day in controlled trials, with average final maintenance doses of 430-530 mg/day 6

Treatment Algorithm

Step 1: Initial Monotherapy Selection

• Start with levetiracetam (1,500 mg oral load or rapid IV loading at doses up to 60 mg/kg) as first choice due to superior treatment retention and minimal drug interactions 3, 1

• If levetiracetam is not tolerated due to psychiatric side effects, switch to carbamazepine or lamotrigine 1, 2

• For women of childbearing potential, prioritize lamotrigine or levetiracetam over valproate due to teratogenicity concerns 1, 4

Step 2: If First Monotherapy Fails

• Switch to an alternative first-line monotherapy (carbamazepine, lamotrigine, or phenytoin) rather than immediately adding a second drug 1

• The American Academy of Neurology recommends prescribing one antiepileptic at a time to minimize adverse effects and drug interactions 1

Step 3: Adjunctive Therapy for Refractory Cases

• Add lacosamide, topiramate, gabapentin, or zonisamide as adjunctive therapy if monotherapy with two different first-line agents has failed 1, 5, 6

• Consider valproate or phenobarbital for highly refractory cases, though phenobarbital performs worse than all other treatments for treatment retention 1, 2

Special Population Considerations

Women of Childbearing Potential

• Avoid valproic acid due to significant teratogenicity risks 1, 4

• Prescribe folic acid routinely when on antiepileptic drugs 1

• Control seizures with monotherapy at minimum effective dose 1

Patients with Intellectual Disability

• Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects 1

Patients with Renal Impairment

• Levetiracetam and gabapentin require dose adjustments, with gabapentin requiring significant dose reduction as it is primarily eliminated unchanged in urine 1

Patients with Liver Disease

• Medications metabolized by the liver (carbamazepine, phenytoin) may require dosage adjustments, while levetiracetam has minimal hepatic metabolism 1

Patients on Multiple Medications

• Lacosamide is preferred when drug interactions are a concern due to its non-enzyme-inducing properties 4

• Avoid enzyme-inducing antiepileptics (carbamazepine, phenytoin, phenobarbital) which can reduce effectiveness of concomitant medications 1

Critical Pitfalls to Avoid

• 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 3

• Do not abruptly discontinue antiepileptic drugs, as this can precipitate withdrawal seizures 4

• 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

• Do not use valproic acid in women who may become pregnant without careful consideration of risks, and check drug interactions regularly 3, 1

• Do not use antiepileptic drugs for prophylaxis in seizure-free patients, such as brain tumor patients without seizure history 4

Common Adverse Effects

• The most commonly reported adverse events across all antiepileptic drugs include drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness, and rash or skin disorders 6

• Levetiracetam: fatigue, dizziness, and rarely pain at infusion site 1

• Lacosamide: mild to moderate dizziness, headache, back pain, somnolence, and injection site pain 1

• Valproate: transient local irritation at injection site, dizziness, thrombocytopenia, and liver toxicity 1