AED recommendations by sezure type
| Seizure type | First-line AEDs | Second-line AEDs | Adjunctive AEDs | Considered additional AEDs | Not recommended |
|---|---|---|---|---|---|
| Focal | CBZ, OXC, LTG | LVT, VPA | CBZ, GBP, LTG, LVT, OXC, VPA, TPM | LCM, PB, PHT, PGB, VGB, ZNS | |
| GTCS | VPA, LTG | CLB, LTG, LVT, VPA, TPM | |||
| Absence | ESM, VPA | LTG | CLB, CZP, LVT, TPM, ZNS | CBZ, OXC, GBP, PHT, PGB, VGB | |
| Myoclonic | VPA | LVT, TPM | CBZ, CZP, ZNS | CBZ, OXC, GBP, PHT, PGB, VGB | |
| Atonic or tonic | VPA | LTG | TPM | CBZ, OXC, GBP, PHT, PGB, VGB |
AED: antiepileptic drug, CBZ: carbamazepine, CLB: clobazam, CZP: clonazepam, ESM: ethosuximide, GBP: gabapentin, GTCS: generalized tonic-clonic seizure, LCM: lacosamide, LTG: lamotrigine, LVT: levetiracetam, OXC: oxcarbazepine, PB: phenobarbital, PGB: pregabalin, PHT: phenytoin, TPM: topiramate, VGB: vigabatrin, VPA: valproate, ZNS: zonisamide.
AED start doses and titration rate
| AED | Titration rate | Initial target maintenance dose (mg/day) | Usual maintenance dose (mg/day) | Frequency of administration |
|---|---|---|---|---|
| PB | Start at 30-50 mg at bedtime and increase if indicated after 10-15 days | 50-100 | 50-200 | 1 time/day |
| PHT | Start at 100-300 mg/day and increase to target dosage over 3-7 days at up to 50 mg/day | 200-300 | 200-400 | 1-2 times/day |
| PRM | Start at 62.5 or 125 mg/day and increase to target dosage over about 3 weeks1 | 500-750 | 500-1500 | 2-3 times/day |
| ESM | Start at 500 mg/day and increase at 5- to 7-day intervals in increments of 250 mg/day | 500-750 | 500-1500 | |
| CBZ | Start at 200 or 400 mg/day and increase to target dosage over 1-4 weeks at up to 200 mg/day | 400-600 | 400-1600 | 2-3 times/day |
| CLB | Start at 5-10 mg/day and increase to 20 mg/day after 1-2 weeks | 10-20 | 10-40 | 1-2 times/day |
| VPA | Start at 500 mg/day and increase at 5- to 7-day intervals in increments of 500 mg/day | 500-1000 | 500-2500 | 2-3 times/day |
| VGB | Start at 250 or 500 mg/day and increase by 500 mg/day over 1-2 weeks | 1000 | 1000-3000 | 1-2 times/day |
| ZNS | Start at 50-100 mg/day, increase to 100 mg/day at interval of 1-2 weeks | 200-300 | 200-500 | 2 times/day |
| LTG | Start at 25 mg/day for 2 week, then increase to 50 mg/day for 2 weeks. Further increases of 50 mg/day every 2 weeks2,3 | 50-150 (monotherapy) | 50-150 (monotherapy or add-on valproate) | 2 times/day (once daily possible with monotherapy and valproate comedication) |
| GBP | Start at 300-900 mg/day and increase to target dosage over 5-10 days | 900-1800 | 900-3600 | 2-3 times/day |
| TPM | Start at 25-50 mg/day and increase in 25- or 50-mg/day increments every 2 weeks | 100 | 100-400 | 2 times/day |
| OXC | Start at 300 mg/day and increase at 2-day intervals by 150 mg/day to target dosage over 1-3 weeks | 600-900 | 600-3000 | 2-3 times/day |
| LEV | Start at 500 or 1000 mg/day and increase at 1- to 2-week intervals at up to 500 mg/day after 2 weeks | 1000-2000 | 1000-3000 | 2 times/day |
| PGB | Start at 50 or 75 mg/day and increase at 3- to 7-day intervals at up to 50-300 mg/day | 150-300 | 150-600 | 2-3 times/day |
| LCM | Start at 100 mg/day and increase to target dosage in increments of 100 mg/day every week | 200-300 | 200-400 | 2 times/day |
| RFN | Start at 400 mg/day and increase every 2-4 days by 400 mg/day | 1200 | 1200-3200 | 2 times/day |
| PRP | Start at 2 mg and increase by 2 mg/day to target dosage at 2-week intervals | 4-8 | 4-12 | 1 time/day |
| BVC | Start at either 50 or 100 mg/day and increase to target dose at intervals of 1-2 weeks | 50-200 | 50-200 | 2 times/day |
AED: antiepileptic drug, BVC: brivaracetam, CBZ: carbamazepine, CLB: clobazam, ESM: ethosuximide, GBP: gabapentin, LCM: lacosamide, LEV: levetiracetam, LTG: lamotrigine, OXC: oxcarbazepine, PB: phenobarbital, PGB: pregabalin, PHT: phenytoin, PRM: primidone, PRP: perampanel, RFN: rufinamide, TPM: topiramate, VGB: vigabatrin, VPA: valproate, ZNS: zonisamide.
1 A faster titration may be used in patients on enzyme-inducing comedication.
2 With Valproate comedication: start at 25 mg on alternate days for 2 weeks, then 25 mg/day for 2 weeks. Further increases of 25-50 mg/day every 2 weeks. Initial target maintenance dose is 50-100 mg/day, usual maintenance dose is 50-150 mg/day.
3 With enzyme inducing comedication: start at 25 or 50 mg/day for 2 weeks. Further increases of 50-100 mg/day every 2 weeks. Initial target maintencance dose is 200-300 mg/day, usual maintenance dose is 200-500 mg/day.
References
- Epilepsy treatment in adults and adolescents: expert opinion, 2016. Epilepsy Behav. 2017;69:186–222. doi: 10.1016/j.yebeh.2016.11.018
- Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data Cochrane Database Syst Rev . 2022 Apr 1;4(4):CD011412. doi: 10.1002/14651858.CD011412.pub4
- Antiepileptic Drug Selection According to Seizure Type in Adult Patients with Epilepsy J Clin Neurol. 2020 Sep 9;16(4):547–555. doi: 10.3988/jcn.2020.16.4.547
- Effect of carbamazepine and oxcarbazepine on serum neuron-specific enolase in focal seizures: a randomized controlled trial. Epilepsy Res. 2017;138:5–10. doi: 10.1016/j.eplepsyres.2017.10.003
- The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1000–1015. doi: 10.1016/S0140-6736(07)60460-7
- The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1016–1026. doi: 10.1016/S0140-6736(07)60461-9
- Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000;55:236–242. doi: 10.1212/wnl.55.2.236
- Valproate monotherapy in the management of generalized and partial seizures. Epilepsia. 1987;28 Suppl 2:S12–S17. doi: 10.1111/j.1528-1157.1987.tb05766.x
- A meta-analysis of levetiracetam for randomized placebo-controlled trials in patients with refractory epilepsy. Neuropsychiatr Dis Treat. 2019;15:905–917. doi: 10.2147/NDT.S188111
- Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy. Epilepsia. 2001;42:539–542. doi: 10.1046/j.1528-1157.2001.31600.x
- Gabapentin as add-on therapy in refractory partial epilepsy: a double- blind, placebo-controlled, parallel-group study. Neurology. 1993;43:2292–2298. doi: 10.1212/wnl.43.11.2292
- Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy. Seizure. 2000;9:486–492. doi: 10.1053/seiz.2000.0444
- The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. Epilepsy Res. 2007;76:6–14. doi: 10.1016/j.eplepsyres.2007.06.002
- Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy. Epilepsia. 2000;41:1597–1607. doi: 10.1111/j.1499-1654.2000.001597.x
- Tiagabine as add-on therapy may be more effective with valproic acid--open label, multicentre study of patients with focal epilepsy. Eur J Neurol. 2005;12:176–180. doi: 10.1111/j.1468-1331.2004.00874.x
- Topiramate in add-on therapy: results from an open-label, observational study. Seizure. 2007;16:593–600. doi: 10.1016/j.seizure.2007.04.007
- Long-term exposure and safety of lacosamide monotherapy for the treatment of partial-onset (focal) seizures: results from a multicenter, open-label trial. Epilepsia. 2016;57:1625–1633. doi: 10.1111/epi.13502
- Brivaracetam (UCB 34714) Neurotherapeutics. 2007;4:84–87. doi: 10.1016/j.nurt.2006.11.004
- Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: a randomized trial. Neurology. 2015;85:950–957. doi: 10.1212/WNL.0000000000001930
- Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev. 2017;2:CD003032. doi: 10.1002/14651858.CD003032.pub3
- Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362:790–799. doi: 10.1056/NEJMoa0902014