Red Flags
- First-ever generalised tonic-clonic seizure with persistent altered consciousness, focal deficit, or recurrent seizures within 24 h — emergency neuroimaging and admission[1]
- Status epilepticus (≥5 min continuous seizure or recurrent seizures without recovery) — IV benzodiazepine then second-line ASM per local protocol; ITU referral[1]
- Suspected non-epileptic seizure (psychogenic) misdiagnosed as epilepsy — review video-EEG before lifelong ASM commitment[1]
- Pregnancy or planning pregnancy with epilepsy — preconception counselling; valproate teratogenicity, switch consideration; folate 5 mg/day[2]
First-line treatment
Interventions
- Confirm syndromic classification before drug choice[1]Focal vs generalised vs combined epilepsy and any specific syndrome (childhood absence, JME, Dravet, Lennox-Gastaut) determine first-line ASM and which drugs to avoid
- Single-drug, low-dose start with slow titration[1]Monotherapy preferred; start at the lowest effective dose with gradual titration to balance seizure control and tolerability; assess response over 8–12 weeks before changing
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Levetiracetam (focal + generalised)[1] | SV2A modulator | Start 250–500 mg PO BD; usual 1000–3000 mg/day in two divided doses | Children ≥6 years: 10 mg/kg BD start; 30–60 mg/kg/day target in two divided doses | First-line in pregnancy planning, focal and generalised epilepsy; behavioural side effects common; renal dose adjustment |
| Lamotrigine (focal + generalised)[1] | Sodium channel blocker | 25 mg PO daily × 2 weeks, 50 mg daily × 2 weeks, then increase by 50–100 mg every 1–2 weeks; usual 200–400 mg/day in two divided doses | Slow titration per age and weight; halve dose with valproate co-medication | Slow titration to avoid Stevens-Johnson syndrome; safer in pregnancy than valproate; may worsen myoclonus in JME |
| Carbamazepine (focal)[1] | Sodium channel blocker | Start 100–200 mg PO BD; usual 600–1200 mg/day in divided doses | 10–20 mg/kg/day in two divided doses; titrate over 2 weeks | First-line monotherapy for focal seizures; HLA-B*1502 screen in Han Chinese, Thai, Malay, South Asian populations to avoid SJS; enzyme inducer |
| Sodium valproate (generalised)[2] | Multiple — GABA potentiation, sodium channel, T-type calcium | Start 500 mg PO daily; usual 1000–2000 mg/day in two divided doses | 10–15 mg/kg/day; titrate to 30 mg/kg/day | Most effective drug for generalised tonic-clonic and absence; CONTRAINDICATED in women of childbearing potential without pregnancy prevention programme; teratogenicity (NTD, neurodevelopmental) |
| Ethosuximide (childhood absence)[1] | T-type calcium channel blocker | Adults rarely use — 500 mg PO daily start, increase by 250 mg weekly; usual 750–2000 mg/day | 10–20 mg/kg/day; up to 40 mg/kg/day if needed | First-line for childhood absence epilepsy without generalised tonic-clonic seizures; superior to lamotrigine for absence |
| Lacosamide (focal)[1] | Slow inactivation sodium channel modulator | 50 mg PO BD start; usual 200–400 mg/day in two divided doses | Children ≥4 years: weight-based per local product information | First-line for focal epilepsy in adults including elderly; once-weekly ECG monitoring with cardiac comorbidity (PR prolongation) |
Levetiracetam (focal + generalised)[1]
SV2A modulator
- Adult
- Start 250–500 mg PO BD; usual 1000–3000 mg/day in two divided doses
- Paediatric
- Children ≥6 years: 10 mg/kg BD start; 30–60 mg/kg/day target in two divided doses
First-line in pregnancy planning, focal and generalised epilepsy; behavioural side effects common; renal dose adjustment
Lamotrigine (focal + generalised)[1]
Sodium channel blocker
- Adult
- 25 mg PO daily × 2 weeks, 50 mg daily × 2 weeks, then increase by 50–100 mg every 1–2 weeks; usual 200–400 mg/day in two divided doses
- Paediatric
- Slow titration per age and weight; halve dose with valproate co-medication
Slow titration to avoid Stevens-Johnson syndrome; safer in pregnancy than valproate; may worsen myoclonus in JME
Carbamazepine (focal)[1]
Sodium channel blocker
- Adult
- Start 100–200 mg PO BD; usual 600–1200 mg/day in divided doses
- Paediatric
- 10–20 mg/kg/day in two divided doses; titrate over 2 weeks
First-line monotherapy for focal seizures; HLA-B*1502 screen in Han Chinese, Thai, Malay, South Asian populations to avoid SJS; enzyme inducer
Sodium valproate (generalised)[2]
Multiple — GABA potentiation, sodium channel, T-type calcium
- Adult
- Start 500 mg PO daily; usual 1000–2000 mg/day in two divided doses
- Paediatric
- 10–15 mg/kg/day; titrate to 30 mg/kg/day
Most effective drug for generalised tonic-clonic and absence; CONTRAINDICATED in women of childbearing potential without pregnancy prevention programme; teratogenicity (NTD, neurodevelopmental)
Ethosuximide (childhood absence)[1]
T-type calcium channel blocker
- Adult
- Adults rarely use — 500 mg PO daily start, increase by 250 mg weekly; usual 750–2000 mg/day
- Paediatric
- 10–20 mg/kg/day; up to 40 mg/kg/day if needed
First-line for childhood absence epilepsy without generalised tonic-clonic seizures; superior to lamotrigine for absence
Lacosamide (focal)[1]
Slow inactivation sodium channel modulator
- Adult
- 50 mg PO BD start; usual 200–400 mg/day in two divided doses
- Paediatric
- Children ≥4 years: weight-based per local product information
First-line for focal epilepsy in adults including elderly; once-weekly ECG monitoring with cardiac comorbidity (PR prolongation)
Safety-net
- Do not stop antiseizure medication abruptly — sudden discontinuation can trigger status epilepticus; taper under specialist supervision over weeks to months[1]
- Any new rash within 8 weeks of starting carbamazepine, lamotrigine, oxcarbazepine, phenytoin, or phenobarbital — stop the drug and seek same-day medical review (concern for severe cutaneous adverse reaction)[1]
- Driving — comply with national epilepsy driving rules; most jurisdictions require a seizure-free interval (often 6–12 months) before licence reinstatement[1]
Referral criteria
- All new-onset suspected epilepsyNeurology / first-seizure clinic[1]
- Drug-resistant epilepsy after adequate trial of two appropriate ASMsTertiary epilepsy centre for surgical and device evaluation[1]
- Woman with epilepsy planning pregnancy or pregnant on ASMJoint epilepsy and obstetric clinic; consider switch from valproate[2]
- Diagnostic uncertainty between epileptic and non-epileptic seizuresVideo-EEG monitoring at specialist centre[1]
Clinical summary
Choice of first antiseizure medication for newly diagnosed focal, generalised, and absence epilepsy in adults and children.