Initial monotherapy for newly diagnosed epilepsy

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.

References

1.ILAE Updated Evidence-Based Guideline on Antiseizure Medications for the Initial Monotherapy of Epilepsy (2018, refreshed 2022); AAN/AES Treatment of New-Onset Epilepsy (2018)
2.Management of Epilepsy in Pregnancy: an ILAE Task Force Report. Epileptic Disorders (2019)