For Clinicians
A practical prescribing checklist and quick-reference decision table for antiepileptic drug selection, grounded in current evidence.
5-Question Prescribing Checklist
Have I classified the epilepsy type?
Focal, generalised, or unknown onset — this determines which drugs are appropriate. Do not prescribe before classification.
Is levetiracetam first-line for this epilepsy type?
For focal epilepsy, SANAD II (2021) shows lamotrigine is superior. For absence epilepsy, ethosuximide or valproate are preferred.
Does the patient have psychiatric comorbidities?
Prior depression, anxiety, aggression, or psychosis significantly increases the risk of neuropsychiatric adverse effects from LEV.
Have I discussed neuropsychiatric risks with the patient and family?
Patients and caregivers should be informed about the 10–20% risk of irritability/aggression and 13% risk of depression before starting LEV.
Do I have a review plan if the first drug fails?
If seizures are not controlled, consider whether the drug choice was appropriate before concluding the epilepsy is drug-resistant (IRE concept).
Quick-Reference Decision Table
*Sodium valproate: contraindicated in women of childbearing potential unless no alternatives (MHRA).
| Clinical Situation | Recommended | Avoid | Evidence |
|---|---|---|---|
| Newly diagnosed focal epilepsy | Lamotrigine (first-line) | LEV (inferior per SANAD II) | SANAD II, Lancet 2021 |
| Newly diagnosed generalised tonic-clonic | Valproate* or Lamotrigine | Carbamazepine (may worsen) | SANAD I, Lancet 2007 |
| Juvenile myoclonic epilepsy (JME) | Valproate* or LEV | Carbamazepine, Phenytoin | NICE CG137 |
| Childhood absence epilepsy | Ethosuximide or Valproate* | LEV, Carbamazepine | Glauser et al., NEJM 2010 |
| Status epilepticus (2nd line) | Valproate, Fosphenytoin, or LEV (equivalent) | No preference — choose based on patient factors | ESETT, NEJM 2019 |
| Patient with psychiatric history | Lamotrigine, Carbamazepine | LEV (high neuropsychiatric risk) | Josephson et al., JAMA Neurology 2019 |
| Women of childbearing potential | Lamotrigine, LEV | Valproate (teratogenic) | MHRA guidance; NICE CG137 |
| Apparent drug-resistant epilepsy | Review initial drug choice — consider IRE | Escalating doses without reassessment | Bašić et al. 2021; Kwan & Brodie 2000 |
Key Reference Cards
Lamotrigine superior to LEV for focal epilepsy (HR 1.32, p=0.018)
LEV = valproate = fosphenytoin in status epilepticus (~50% response each)
47% seizure-free with first drug; only 11% after first drug fails
Current UK epilepsy guidelines — AED selection by seizure type