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 seizure or recurrent without recovery) — IV benzodiazepine then second-line ASM; ITU referral^[1]
Suspected non-epileptic seizure (psychogenic) misdiagnosed as epilepsy — review with video-EEG before lifelong ASM^[1]
Pregnancy or planning pregnancy with epilepsy — preconception counselling; valproate teratogenicity; switch consideration; folate 5 mg/day^[1]

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; assess response over 8–12 weeks before changing or adding
Consider AED withdrawal after 2 years seizure-free^[1]
Gradual taper over 3–6 months under specialist supervision; relapse risk varies by syndrome, EEG findings, MRI lesion presence; counsel about driving rules during and after taper

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	First-line in pregnancy planning, focal and generalised epilepsy; behavioural side effects common; renal dose adjustment
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	First-line monotherapy for focal seizures; HLA-B*1502 screen in Han Chinese, Thai, Malay, South Asian populations to avoid SJS; enzyme inducer
Oxcarbazepine (focal)^[1]	Sodium channel blocker	Start 300 mg PO BD; usual 900–1800 mg/day	Children ≥6: 8–10 mg/kg/day; titrate to 30 mg/kg/day	Alternative to carbamazepine; less enzyme induction; hyponatraemia risk; HLA-B*1502 caution
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	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
Sodium valproate (generalised — restricted)^[1]	Multiple-mechanism ASM	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	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

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

First-line in pregnancy planning, focal and generalised epilepsy; behavioural side effects common; renal dose adjustment

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

First-line monotherapy for focal seizures; HLA-B*1502 screen in Han Chinese, Thai, Malay, South Asian populations to avoid SJS; enzyme inducer

Oxcarbazepine (focal)^[1]

Sodium channel blocker

Adult: Start 300 mg PO BD; usual 900–1800 mg/day
Paediatric: Children ≥6: 8–10 mg/kg/day; titrate to 30 mg/kg/day

Alternative to carbamazepine; less enzyme induction; hyponatraemia risk; HLA-B*1502 caution

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
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

Sodium valproate (generalised — restricted)^[1]

Multiple-mechanism ASM

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: 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

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^[1]
Diagnostic uncertainty between epileptic and non-epileptic seizuresVideo-EEG monitoring at specialist centre^[1]

Clinical summary

Diagnosis, syndromic classification, and choice of first antiseizure medication for adults and children with newly diagnosed epilepsy.

References

1.Indian Academy of Neurology Guidelines for Epilepsy (2023); IAN Epilepsy Workgroup Consensus (2023)