What is the typical treatment for epilepsy?

Treatment of Epilepsy

For focal onset seizures, lamotrigine is the first-line treatment, with levetiracetam as an alternative if there is no psychiatric history; for generalized tonic-clonic seizures, sodium valproate is first-line, but must be avoided in women of childbearing potential, making lamotrigine or levetiracetam the preferred alternatives. 1, 2

Initial Treatment Selection by Seizure Type

Focal Onset Seizures

Lamotrigine demonstrates superior efficacy and tolerability compared to other antiseizure drugs for focal epilepsy. 2, 3

• Lamotrigine should be offered as first-line monotherapy, with the best profile for treatment failure and seizure control 2, 3
• Levetiracetam is an appropriate alternative first-line option with similar efficacy to lamotrigine (no significant difference in treatment failure rates), particularly when psychiatric comorbidities are absent 4, 2
• Carbamazepine is recommended by WHO guidelines as first-line for partial onset seizures, particularly in resource-limited settings, though lamotrigine shows better tolerability 5, 1
• Zonisamide met non-inferiority criteria compared to lamotrigine but showed higher treatment failure rates in per-protocol analysis 3

Generalized Tonic-Clonic Seizures

Sodium valproate remains the most effective first-line treatment for generalized epilepsy, but carries significant teratogenic risks. 5, 2, 3

• Valproate demonstrates superior seizure control compared to all other treatments for generalized epilepsy (hazard ratio 1.68 vs levetiracetam for 12-month remission) 3
• For women of childbearing potential, valproate must be avoided due to significantly increased risks of fetal malformations and neurodevelopmental delay 5, 1
• Lamotrigine or levetiracetam should be used as first-line alternatives in women of childbearing age, accepting slightly lower seizure control rates in exchange for safety 2, 3

Standard Monotherapy Approach

Monotherapy with a single antiseizure drug should always be the initial treatment strategy. 5, 1

• Start with one standard antiepileptic drug (carbamazepine, phenobarbital, phenytoin, or valproic acid for resource-limited settings; lamotrigine, levetiracetam, or valproate for standard settings) 5
• Optimize dosing of the first drug to maximum tolerated dose before considering treatment failure 1
• If the first drug fails due to lack of efficacy, switch to a second monotherapy agent rather than adding a second drug 5
• Polytherapy should only be considered after failure of at least two appropriate monotherapy trials 5, 1

When to Initiate Treatment

Antiepileptic drugs should be strongly considered after two unprovoked seizures, but not routinely prescribed after a single first seizure. 5, 1, 4

• Treatment after a single unprovoked seizure should be considered when: the seizure occurred during sleep, epileptiform activity is present on EEG, or a structural lesion is visible on brain MRI 4
• After two unprovoked seizures, treatment should be initiated as approximately 60-70% of patients will achieve long-term remission 4, 2

Treatment Duration and Discontinuation

Consider discontinuing antiepileptic drugs after 2 seizure-free years, weighing clinical, social, and personal factors with patient and family involvement. 5, 1

• The decision to withdraw treatment requires consideration of seizure type, epilepsy syndrome, EEG findings, and the impact of seizure recurrence on the patient's life 5
• Gradual tapering is essential to minimize withdrawal seizure risk 5

Special Populations and Considerations

Women with Epilepsy

Women with epilepsy require seizure control with monotherapy at minimum effective dose, avoiding valproic acid whenever possible. 5

• Valproic acid should be avoided due to teratogenicity 5
• Antiepileptic drug polytherapy should be avoided 5
• Folic acid should be routinely taken when on antiepileptic drugs 5
• Standard breastfeeding recommendations remain appropriate for phenobarbital, phenytoin, carbamazepine, and valproic acid 5

Intellectual Disability

People with intellectual disability and epilepsy should receive the same investigations and treatments as the general population, with drug choice individualized by seizure type. 5

• Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital when available, due to lower risk of behavioral adverse effects 5

Resource-Limited Settings

In low- and middle-income countries, phenobarbital should be offered as first-line treatment if availability can be assured, given acquisition costs. 5

• Carbamazepine should be preferentially offered to children and adults with partial onset seizures when available 5
• EEG and neuroimaging should not be used routinely for diagnosis and starting treatment in non-specialized settings 5
• Non-specialist health care providers can be trained to recognize and diagnose convulsive epilepsy 5

Common Pitfalls to Avoid

• Never use neuromuscular blockers alone (such as rocuronium) for seizures, as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 6
• Do not skip directly to polytherapy without adequate trials of at least two monotherapy agents at maximum tolerated doses 5, 1
• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) when possible due to significant drug interactions, effects on bone health, and cardiovascular risks from hyperlipidemia 4
• Do not routinely order EEG and neuroimaging before starting treatment in resource-limited settings; clinical diagnosis based on detailed seizure history is sufficient 5

Adjunctive Treatment Options

Information on avoiding high-risk activities and first aid should be routinely provided to patients and families. 5

• Psychological treatments such as relaxation therapy, cognitive behavioral therapy principles, psychoeducational programs, and family counseling may be considered as adjunctive treatment 5

Newer Antiseizure Medications

Topiramate and other newer agents are approved for both monotherapy and adjunctive therapy but are generally reserved for second-line use. 7

• Topiramate is indicated as initial monotherapy in patients 10 years and older with partial onset or primary generalized tonic-clonic seizures 7
• Topiramate carries risks of metabolic acidosis (32% incidence at 400 mg/day) requiring baseline and periodic serum bicarbonate monitoring 7
• Levetiracetam's most common adverse events include somnolence, asthenia, infection, and dizziness in adults; somnolence, accidental injury, hostility, nervousness, and asthenia in children 8