Treatment Options
Better Alternatives
An evidence-based comparison of antiepileptic drugs by epilepsy type, with drug profiles for each major agent.
Quick-Reference Guide by Epilepsy Type
*Sodium valproate: highly teratogenic — avoid in women of childbearing potential unless no suitable alternatives exist (MHRA guidance).
Treatment depends on a confirmed seizure and epilepsy classification. Lacosamide is an important focal-seizure option, but current guidance places it after other monotherapy choices; brivaracetam is primarily an add-on option for focal-onset seizures rather than a first-line generalized or absence medicine.
| Epilepsy Type | First Line | Second Line | Avoid |
|---|---|---|---|
| Focal (partial onset) | Lamotrigine, LEV; Lacosamide (add-on) | Carbamazepine, Oxcarbazepine, Zonisamide; Brivaracetam (add-on) | — |
| Generalised tonic-clonic | Sodium Valproate*, Lamotrigine | LEV, Topiramate | Carbamazepine (may worsen) |
| Absence | Ethosuximide, Sodium Valproate* | Lamotrigine | Carbamazepine, LEV |
| Myoclonic (JME) | Sodium Valproate*, LEV | Topiramate | Carbamazepine, Phenytoin |
| Unknown onset | Lamotrigine, LEV | Valproate* | — |
Drug Profiles
Lamotrigine
Mechanism: Sodium channel blocker; stabilises neuronal membranes and reduces glutamate release.
Evidence: Superior to levetiracetam for focal epilepsy (SANAD II, HR 1.32). First-line for focal and generalised epilepsy.
Advantages: Broad spectrum, well-tolerated, no cognitive impairment, safe in pregnancy (relative to valproate).
Disadvantages: Slow titration required (risk of Stevens-Johnson syndrome if titrated too fast). Oral contraceptives reduce lamotrigine levels.
Key citation: SANAD II, The Lancet 2021; NICE CG137
Carbamazepine
Mechanism: Sodium channel blocker; reduces high-frequency repetitive firing.
Evidence: Established first-line for focal epilepsy. SANAD I showed it was superior to valproate, topiramate, gabapentin, and oxcarbazepine for focal epilepsy.
Advantages: Highly effective for focal seizures; long track record; inexpensive.
Disadvantages: Multiple drug interactions (CYP3A4 inducer). May worsen generalised epilepsies. Hyponatraemia risk.
Key citation: SANAD I, The Lancet 2007; NICE CG137
Sodium Valproate
Mechanism: Multiple mechanisms: sodium channel blockade, GABA enhancement, T-type calcium channel inhibition.
Evidence: Most effective drug for idiopathic generalised epilepsies (IGE), including JME and absence. SANAD I showed superiority for generalised epilepsy.
Advantages: Broad spectrum; highly effective for IGE; well-established.
Disadvantages: Highly teratogenic — MUST NOT be used in women of childbearing potential unless no alternatives. Weight gain, hair loss, tremor.
Key citation: SANAD I, The Lancet 2007; NICE CG137; MHRA guidance
Ethosuximide
Mechanism: T-type calcium channel blocker; reduces thalamo-cortical oscillations underlying absence seizures.
Evidence: First-line for childhood absence epilepsy (CAE). Glauser et al. (NEJM 2010) showed superiority over valproate and lamotrigine for attention outcomes in CAE.
Advantages: Highly specific and effective for absence seizures; good cognitive profile.
Disadvantages: Only effective for absence seizures — not for tonic-clonic or focal seizures.
Key citation: Glauser et al., NEJM 2010; NICE CG137
Lacosamide
Mechanism: Enhances the slow inactivation of voltage-gated sodium channels, a comparatively distinctive mechanism that differs from the fast-inactivation effects of carbamazepine and lamotrigine.
Evidence: Established for focal-onset seizures as adjunctive treatment and a later-line monotherapy option in NICE NG217; it is not established as first-line treatment for absence or generalized myoclonic epilepsy.
Advantages: Useful focal-seizure option; IV and oral formulations; few pharmacokinetic interactions; its slow-channel mechanism is pharmacologically distinct from traditional fast sodium-channel blockers.
Disadvantages: Dizziness, diplopia, nausea and dose-related cardiac-conduction effects can occur. Do not assume that a different sodium-channel mechanism makes it suitable for every generalized epilepsy syndrome; specialist classification is essential.
Key citation: NICE NG217 (2022, updated 2025); Curia et al., CNS Drug Reviews 2009
Zonisamide
Mechanism: Broad-spectrum antiseizure medicine with effects including sodium-channel and T-type calcium-channel modulation, plus carbonic-anhydrase inhibition.
Evidence: NICE lists zonisamide as a second-line monotherapy option for focal-onset seizures when lamotrigine or levetiracetam is unsuccessful or unsuitable, and as an add-on option for focal seizures.
Advantages: Once- or twice-daily dosing; broad-spectrum activity; useful option when focal seizures persist or other agents are not tolerated.
Disadvantages: Reduced appetite, weight loss, cognitive or psychiatric effects, kidney stones, metabolic acidosis and oligohidrosis/heat intolerance are important risks to discuss and monitor.
Key citation: NICE NG217; Zonisamide product information
Brivaracetam
Mechanism: High-affinity SV2A ligand that modulates synaptic vesicle release; pharmacologically related to levetiracetam but more selective for SV2A.
Evidence: An evidence-supported add-on option for drug-resistant focal-onset seizures. Current regulatory indications and NICE recommendations do not support presenting it as first-line monotherapy for generalized or absence epilepsy; use in genetic generalized epilepsies remains specialist/off-label and evidence-limited.
Advantages: Rapid titration is usually possible; IV and oral formulations; fewer enzyme-inducing interactions than several older antiseizure medicines; some patients experience fewer behavioural effects than with levetiracetam, though this is not guaranteed.
Disadvantages: Somnolence, dizziness, fatigue and behavioural or psychiatric adverse effects can occur. Cost, access and the limited evidence outside focal-onset epilepsy should be considered.
Key citation: NICE NG217; EMA Briviact product information
Levetiracetam
Mechanism: SV2A binding; modulates synaptic vesicle release.
Evidence: Inferior to lamotrigine for focal epilepsy (SANAD II). Equivalent to valproate and fosphenytoin in status epilepticus (ESETT). Appropriate for myoclonic seizures in JME.
Advantages: No titration required; IV formulation available; minimal pharmacokinetic interactions; broad spectrum.
Disadvantages: Inferior to lamotrigine for focal epilepsy. 20–35% neuropsychiatric adverse events. Not first-line for absence epilepsy.
Key citation: SANAD II, The Lancet 2021; ESETT, NEJM 2019