What is the typical treatment for epilepsy?

Treatment of Epilepsy

For focal onset seizures, lamotrigine is the preferred first-line monotherapy, followed by carbamazepine or levetiracetam (if no psychiatric history), while for generalized tonic-clonic seizures, sodium valproate remains the gold standard, with lamotrigine or levetiracetam as alternatives particularly for women of childbearing potential. 1, 2

Initial Treatment Selection by Seizure Type

Focal Onset Seizures

Lamotrigine demonstrates superior treatment outcomes compared to other antiseizure drugs for focal epilepsy. 2

• Lamotrigine should be offered as first-line treatment based on high-certainty evidence showing better performance than most other treatments in terms of treatment failure for any reason and adverse events 2
• Carbamazepine is an acceptable first-line alternative, particularly for children and adults with partial onset seizures, with an initial dose of 200 mg twice daily for adults and children >12 years 3, 1
• Levetiracetam performs similarly to lamotrigine (HR 1.01,95% CI 0.88-1.20 for treatment failure) and can be considered if there is no history of psychiatric disorder 2, 4
• Oxcarbazepine is another option but shows inferior performance compared to lamotrigine (HR 1.30,95% CI 1.02-1.66) 2

Generalized Tonic-Clonic Seizures

Sodium valproate remains the most effective first-line treatment for generalized epilepsy. 1, 2

• Valproic acid is the preferred first-line treatment for generalized seizures based on superior efficacy 1, 2
• Lamotrigine and levetiracetam are the most suitable alternatives when valproate is contraindicated, showing no significant differences in treatment failure compared to valproate (HR 1.06 and 1.13 respectively) 2, 5
• For women of childbearing potential, valproate should be avoided due to teratogenicity risks, and lamotrigine or levetiracetam should be used instead 1, 4, 6

Monotherapy vs. Polytherapy

Monotherapy with standard antiepileptic drugs should be the initial approach. 3, 1

• Start with a single antiepileptic drug (carbamazepine, phenobarbital, phenytoin, or valproic acid) 3
• Monotherapy minimizes side effects and drug interactions compared to polytherapy 1
• Only consider adding a second drug after adequate trials of at least two first-line agents as monotherapy at maximum tolerated doses 3

When to Initiate Treatment

Treatment should be strongly considered after two unprovoked seizures, but may be initiated after a single seizure in high-risk situations. 4, 7

• Do not routinely prescribe antiepileptic drugs after a first unprovoked seizure unless high risk for recurrence 3, 1
• High-risk features include: history of brain insult, epileptiform abnormalities on EEG, structural lesion on neuroimaging, or seizure occurring during sleep 4, 7
• Treatment is indicated after two or more unprovoked seizures 4

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. 3

• Phenobarbital is the most cost-effective option in resource-limited settings 3
• If available, carbamazepine should be preferentially offered to children and adults with partial onset seizures 3
• Non-specialist health care providers can be trained to recognize and diagnose convulsive epilepsy 3

Treatment Duration and Discontinuation

Consider discontinuing antiepileptic drugs after 2 seizure-free years. 3, 1

• The decision to withdraw treatment should involve consideration of clinical, social, and personal factors 3
• Involve the patient and family in the decision-making process 3

Common Pitfalls to Avoid

• Never use neuromuscular blockers alone for seizures, as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 8
• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) when possible due to significant drug interactions, effects on lipid metabolism, and acceleration of osteoporosis 4
• Do not routinely use EEG and neuroimaging for diagnosis and starting treatment in non-specialized settings; clinical diagnosis based on detailed seizure history is sufficient 3, 1
• Avoid valproate in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 1, 4, 6

Monitoring and Adverse Effects

The most commonly reported adverse events include drowsiness/fatigue, headache, gastrointestinal disturbances, dizziness, and rash, though reporting varies significantly across drugs 2

• Lamotrigine: adverse reactions reported by 33% of participants 5
• Levetiracetam: adverse reactions reported by 41-44% of participants, including somnolence, asthenia, hostility, and nervousness 9, 5
• Valproate: adverse reactions reported by 37% of participants, with hepatotoxicity risk requiring liver function monitoring 5

Special Populations

For women with epilepsy, seizures should be controlled with monotherapy at minimum effective dose, avoiding valproic acid if possible. 3

• Folic acid should routinely be taken when on antiepileptic drugs 3
• Standard breastfeeding recommendations remain appropriate for phenobarbital, phenytoin, carbamazepine, and valproic acid 3

For people with intellectual disability and epilepsy, consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects. 3

Refractory Epilepsy

If trials of more than two antiepileptic drugs do not control seizures, refer to an epilepsy center for evaluation of surgical options. 7

• Epilepsy surgery renders 60-70% of patients with temporal lobe epilepsy free of disabling seizures 7
• Seizure freedom is achieved in approximately 60-70% of all patients with medical therapy 4