What is the recommended initial management—including first‑line antiseizure medication choice, dosing, titration, baseline laboratory monitoring, and follow‑up—for a newly diagnosed adult with focal (partial) seizures?

Initial Management of Newly Diagnosed Focal Seizures in Adults

For newly diagnosed adult focal (partial) seizures, start with carbamazepine, lamotrigine, or levetiracetam as first-line monotherapy, with the specific choice guided by patient sex, psychiatric history, and comorbidities. 1, 2, 3

First-Line Antiseizure Medication Selection

The NICE guidelines explicitly recommend carbamazepine as a first-line option for partial onset seizures, working through voltage-gated sodium channel blockade 1. However, recent comparative evidence demonstrates that oxcarbazepine and lamotrigine have equal efficacy with superior tolerability profiles compared to older agents 2, 3.

Medication Choice Algorithm:

• Lamotrigine or oxcarbazepine: Preferred first-line for most patients with focal epilepsy, particularly women of childbearing potential, due to lower teratogenic risk and favorable tolerability 1, 2, 3

• Levetiracetam: Suitable first-line alternative if no history of psychiatric disorders (depression, anxiety, psychosis), as it can exacerbate these conditions 2, 3

• Carbamazepine: Traditional first-line option but avoid in patients with cardiac disease, osteoporosis risk, or those taking multiple medications due to significant cytochrome P450 enzyme induction causing drug interactions and metabolic complications 1, 2

Critical pitfall: Never use valproate as first-line for focal seizures in women of childbearing potential without explicit discussion of teratogenic risks and contraceptive measures 1. Lamotrigine and levetiracetam are safer alternatives in this population 1.

Dosing and Titration Protocols

Lamotrigine:

• Initial dose: 25 mg daily for 2 weeks 3
• Titration: Increase to 50 mg daily for weeks 3-4, then increase by 50 mg every 1-2 weeks 3
• Target maintenance: 200-400 mg daily in 1-2 divided doses 3
• Key consideration: Slow titration is essential to minimize risk of serious rash (Stevens-Johnson syndrome) 3

Levetiracetam:

• Initial dose: 500 mg twice daily 3
• Titration: Increase by 500 mg twice daily every 2 weeks as needed 3
• Target maintenance: 1000-1500 mg twice daily (maximum 3000 mg/day) 3
• Advantage: Can be titrated rapidly without slow dose escalation 3

Carbamazepine:

• Initial dose: 200 mg twice daily 3
• Titration: Increase by 200 mg/day every week 3
• Target maintenance: 800-1200 mg daily in 2-3 divided doses 3

Baseline Laboratory Monitoring

Before initiating therapy, obtain:

• Complete blood count (CBC): Particularly important for carbamazepine due to risk of aplastic anemia and agranulocytosis 3
• Comprehensive metabolic panel: Including liver function tests and electrolytes, especially for valproate and carbamazepine 3
• Pregnancy test: For all women of childbearing potential before starting any antiseizure medication 1, 2
• Baseline EEG: To document epileptiform activity and guide diagnosis 4, 5
• Brain MRI (preferred) or CT: To identify structural lesions or underlying etiology in essentially any patient with focal seizures 4, 5

Routine monitoring of drug levels is not recommended as it does not correlate with reduction in adverse effects or improvement in effectiveness 6.

Follow-Up Schedule and Monitoring

Initial Follow-Up (First 3 Months):

• Week 2-4: Assess for early adverse effects, particularly rash with lamotrigine, behavioral changes with levetiracetam, or dizziness/sedation with carbamazepine 2, 3
• Monthly visits: During titration phase to assess seizure control and tolerability 6
• Question about seizure occurrences at each visit: This is the primary monitoring tool for treatment efficacy 7

Long-Term Monitoring:

• Every 3-6 months: Once stable on maintenance dose 6
• Monitor for: Seizure frequency, medication adherence, adverse effects, and precipitating factors (sleep deprivation, alcohol use, medication non-compliance) 7
• No routine drug level monitoring: Only check levels if questioning compliance, breakthrough seizures despite apparent adequate dosing, or suspected toxicity 7, 6

Treatment Goals and Expectations

Seizure freedom is achieved in approximately 60-70% of patients with appropriate monotherapy 2. The principle of epilepsy management is monotherapy at maximally tolerated doses before considering combination therapy 1, 5.

When to Escalate Treatment:

• Optimize current medication to maximum tolerated dose before adding a second agent 7
• Verify medication compliance by checking serum drug levels if breakthrough seizures occur 7
• Search for precipitating factors: Sleep deprivation, alcohol, intercurrent illness 7
• Consider alternative monotherapy if first agent fails due to lack of efficacy or intolerable side effects 3

Critical Management Principles

Never prescribe antiepileptic drugs routinely after a single unprovoked seizure unless specific risk factors are present (epileptiform EEG abnormalities, structural brain lesion, nocturnal seizure, or epileptic syndrome) 1, 6. Delaying therapy until a second seizure does not affect long-term remission rates 6.

Avoid phenobarbital as first-line treatment, as it performs significantly worse than all other options for both partial and generalized seizures 1.

Consider enzyme-inducing effects: Carbamazepine and phenytoin can worsen comorbid coronary and cerebrovascular disease by causing hyperlipidemia and accelerating metabolism of concomitant medications, and they facilitate development of osteopenia and osteoporosis 2.

Special Populations

Women of Childbearing Potential:

• First choice: Lamotrigine or levetiracetam 1, 2
• Avoid: Valproate due to significantly increased risks of fetal malformations and neurodevelopmental delay 1, 7
• Counsel: All women about teratogenic risks before starting any antiseizure medication 6

Patients with Psychiatric Comorbidities:

• Avoid levetiracetam: If history of depression, anxiety, or psychosis 2
• Consider lamotrigine: May have mood-stabilizing properties 3

Elderly or Medically Complex Patients:

• Prefer levetiracetam or lamotrigine: Minimal drug interactions and no hepatic enzyme induction 2, 3
• Avoid carbamazepine: Significant drug interactions and cardiovascular effects 2