What is the first line of treatment for a patient with recurrent seizures?

First-Line Treatment for Recurrent Seizures

For patients with recurrent seizures (epilepsy), antiepileptic drug (AED) monotherapy should be initiated, with the specific agent selected based on seizure type: carbamazepine for partial onset seizures or valproate for generalized onset seizures. 1

Initial Treatment Strategy

Seizure Type-Specific Selection

For partial onset seizures:

• Carbamazepine is the recommended first-line agent, working through voltage-gated sodium channel blockade 1
• Start at low doses and titrate upward to the low maintenance dose to minimize adverse effects 2

For generalized onset seizures:

• Valproate is the definitive first-line treatment recommended by NICE and other guidelines, with multiple mechanisms including sodium channel blockade, GABA enhancement, and T-type calcium channel modulation 1
• Initial dosing is 10-15 mg/kg/day, increased by 5-10 mg/kg/week to achieve optimal clinical response 3
• Ordinarily, optimal response is achieved at daily doses below 60 mg/kg/day 3

Alternative First-Line Options

For women of childbearing potential:

• Lamotrigine or levetiracetam are suitable alternatives to valproate due to lower teratogenic risk 1
• Valproate should not be prescribed without explicit discussion of teratogenic risks and contraceptive measures 1

Monotherapy Principles

Start with a single agent:

• Up to 70% of people developing epilepsy may expect to become seizure free with optimum AED monotherapy 4
• Most patients are controlled on a single AED 4
• Monotherapy is preferred to minimize adverse effects and drug interactions 1, 2

Titration approach:

• Begin at low doses and titrate to the low maintenance dose initially 2
• Avoid drug loading except for emergency treatment 2
• If seizures continue, titrate to the limit of tolerability, which achieves additional seizure control in approximately 20% of patients 2

When First-Line Therapy Fails

If the initial AED is ineffective:

• Switch to an average dose of another first-line AED rather than immediately adding a second drug 2
• If trials of more than two AEDs do not control seizures, additional AEDs are unlikely to be effective, and referral to an epilepsy center should be considered 5

Add-on therapy considerations:

• A small proportion of patients requires a combination of two agents 4
• Add-on therapy with a second drug may be viable if the first drug is relatively well tolerated 4
• Slowly reduce the dose of the first drug before adding another to avoid drug overload 2

Critical Pitfalls to Avoid

Never use phenobarbital as first-line treatment:

• Phenobarbital performs significantly worse than all other options for treatment withdrawal in both partial and generalized seizures 1

Avoid unnecessary treatment initiation:

• AEDs should not be routinely prescribed after a single unprovoked seizure 1
• Starting AEDs may not be necessary for seizures induced by precipitation or predisposing factors or for benign epilepsies with rare or mild seizures 2

Prevent overtreatment:

• Avoid dosing to the limit of tolerability if it is not beneficial; reduce the dose instead 2
• If the patient does not benefit unequivocally from two-drug therapy within 3 months (approximately 75% will not benefit), slowly transfer to monotherapy of the second drug 2

Therapeutic Monitoring

Target therapeutic levels:

• For valproate, the therapeutic range is commonly considered 50-100 μg/mL of total valproate, though some patients may be controlled with lower or higher concentrations 3
• Therapeutic drug monitoring should guide dose adjustments, particularly when using valproate, phenytoin, or carbamazepine 6