Remarks y As ASM choice depends on seizure semiology, outcomes are reported separately for focal onset seizures (focal seizures with or without awareness, focal to bilateral tonic-clonic seizures) and generalized onset tonic-clonic seizures (with or without other generalized seizure types such as myoclonus or absence seizures). y All ASMs considered (carbamazepine, lamotrigine, oxcarbazepine, topiramate, gabapentin, sodium valproate, levetiracetam, lacosamide, zonisamide, phenytoin, phenobarbital) are effective in controlling seizures. y Lamotrigine, topiramate, sodium valproate, levetiracetam, lacosamide, zonisamide and phenytoin are considered broad-spectrum ASMs effective against multiple seizure types. Carbamazepine and oxcarbazepine are ASMs mainly utilized for focal onset seizures. Carbamazepine and oxcarbazepine can be effective against generalized tonic-clonic seizures in people with generalized onset epilepsy, although they may exacerbate other seizure types in these individuals. Gabapentin is not an appropriate medicine in generalized epilepsy and should only be considered in those with focal onset seizures. y No systematic review of RCTs comparing these ASMs with placebo was found. It is considered unethical to conduct RCTs comparing standard ASMs, especially as monotherapy, with placebo in established epilepsy as epilepsy should be treated to decrease morbidity and premature mortality. y Both levetiracetam and sodium valproate are effective against all types of seizures, and hence may be ASMs of choice when the type of seizure/epilepsy syndrome is not clear. y All ASMs are associated with adverse effects. Phenobarbital is associated with a higher risk of short- and long-term tolerability problems. y When taken during pregnancy, sodium valproate is associated with a markedly higher risk of fetal malformations. Sodium valproate (valproic acid) has also been associated with hepatic sideeffects, in terms of raised transaminases and elevated ammonia levels. Sodium valproate is contraindicated in individuals with liver disease. y Phenytoin, despite being used as a first-line drug in some places, has a problematic pharmacokinetic profile. Phenytoin has associated risks of arrhythmia and hypotension and can be difficult to administer in adults with comorbid cardiac conditions. y Most trials excluded women known to be pregnant. Seizures in pregnant women can be due to eclampsia, which requires different treatment strategies.

Implementation considerations y The choice of medicine is affected by a number of factors, including seizure semiology, comorbidities, availability, cost and side-effects. y There are feasibility and affordability issues; lacosamide is not currently on the WHO EML (13) or the EMLc (132). y Phenobarbital, being a controlled substance, faces strict regulations in many countries which affects its accessibility