How should a patient with newly diagnosed epilepsy be initially treated and managed, including selection of antiepileptic drugs based on seizure type and follow‑up recommendations?

Initial Treatment and Management of Newly Diagnosed Epilepsy

For a patient with newly diagnosed epilepsy (two or more unprovoked seizures), initiate antiepileptic drug monotherapy immediately, selecting the agent based on seizure type: use carbamazepine or lamotrigine for focal seizures in adults, and valproate for generalized seizures (except in women of childbearing potential). 1, 2

When to Initiate Antiepileptic Drug Therapy

After a single unprovoked seizure:

• Do not routinely start antiepileptic drugs in the emergency department for patients who have returned to baseline neurologic status without evidence of brain disease or injury 3
• Consider initiating treatment only if high-risk features are present: 4, 5
  • Epileptiform abnormalities on EEG
  • Focal structural lesion on neuroimaging
  • History of remote neurologic insult (stroke, trauma, anoxia)
  • Family history of epilepsy
  • Nocturnal seizures
• Patients with these risk factors have a 60-70% recurrence risk and should receive treatment 4
• Without risk factors, recurrence risk is only 20-30%, and treatment can be deferred until a second seizure occurs 4, 5

After two or more unprovoked seizures (epilepsy diagnosis):

• Initiate antiepileptic drug therapy immediately 2, 6

Drug Selection Based on Seizure Type

For Focal (Partial) Seizures:

Adults:

• First-line options: Carbamazepine or lamotrigine 1
• Alternative options: Oxcarbazepine, levetiracetam, gabapentin, topiramate, or zonisamide 4, 2

Children (≥10 years):

• First-line: Oxcarbazepine 1

Elderly patients:

• First-line: Lamotrigine or gabapentin (better tolerability profile) 1

For Generalized Seizures:

Primary generalized tonic-clonic, absence, or myoclonic seizures:

• First-line: Valproate 1, 2
• Alternative options: Lamotrigine or topiramate 2
• Critical caveat: Avoid valproate in women of childbearing age due to teratogenic risk; use lamotrigine instead 1

Juvenile myoclonic epilepsy:

• Levetiracetam is highly effective as adjunctive therapy, with 60.4% of patients achieving ≥50% reduction in myoclonic seizure days at 3000 mg/day 7

Dosing Strategies

Valproate (for generalized seizures):

• Initial dose: 15 mg/kg/day 8
• Titration: Increase by 5-10 mg/kg/week until seizures controlled 8
• Target dose: Usually below 60 mg/kg/day (maximum 60 mg/kg/day) 8
• Therapeutic level: 50-100 mcg/mL 8
• Divide doses if total daily dose exceeds 250 mg 8

Levetiracetam (for focal or generalized seizures):

• Target dose: 3000 mg/day in two divided doses 7
• Titration period: 4 weeks to reach target dose 7
• Effective for partial seizures, myoclonic seizures in JME, and primary generalized tonic-clonic seizures 7

Carbamazepine/Oxcarbazepine (for focal seizures):

• Start at low doses and titrate based on clinical response 4, 1
• Monitor for drug interactions, particularly with other antiepileptic drugs 8

Critical Management Principles

Always use monotherapy initially:

• Monotherapy is preferable to reduce adverse effects and drug interactions 4, 2
• If first monotherapy fails, switch to alternative monotherapy before considering combination therapy 1

Do not routinely monitor drug levels:

• Routine monitoring of antiepileptic drug levels is not correlated with improved outcomes or reduced adverse effects 5
• Check levels only when: 8
  • Seizures are not controlled despite adequate dosing
  • Suspected toxicity or non-compliance
  • Significant drug interactions are present

Avoid these common pitfalls:

• Do not start antiepileptic drugs for acute symptomatic seizures (provoked seizures from acute illness, metabolic derangement, or intoxication)—treat the underlying cause instead 9, 2
• Do not use oxcarbazepine for acute status epilepticus management 3
• Do not perform routine EEG in the emergency department unless diagnosis is uncertain 9

Follow-Up Recommendations

Initial follow-up:

• Arrange neurology consultation within 2-4 weeks of diagnosis 6
• Obtain baseline EEG if not already performed 5, 2
• Obtain brain MRI to identify structural lesions (unless already done) 5, 2

Ongoing monitoring:

• Assess seizure frequency, medication adherence, and adverse effects at each visit 6
• Monitor for cognitive and behavioral effects of antiepileptic drugs 5
• If seizures persist after trials of two appropriate monotherapies, refer to epilepsy center for surgical evaluation 2

Counseling on safety:

• Advise patients to refrain from driving for at least 3 months or until seizures are controlled (varies by state law) 5
• Avoid high-risk activities: swimming alone, working at heights, operating heavy machinery 4, 5
• Counsel on seizure triggers: sleep deprivation, alcohol use, photic stimuli (in generalized epilepsy) 4

Special Populations

Women of childbearing potential:

• Avoid valproate due to teratogenic risk 1
• Use lamotrigine, levetiracetam, or oxcarbazepine as first-line alternatives 1
• Counsel about contraception and pregnancy planning before conception 5, 6

Patients with depression:

• SSRIs and SNRIs (sertraline, citalopram, escitalopram, venlafaxine, duloxetine) are safe first-line antidepressants with low seizure risk 10

Duration of Treatment

Consider discontinuation only after:

• Minimum of 2 consecutive years of complete seizure freedom 11
• Decision should be made jointly with patient and family, weighing risks and benefits 11
• Taper gradually over weeks to months 11