Clinical Pharmacology of Modern Antiepileptic Drugs



  • D Samba Reddy


This article describes current antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures.  Epileptic seizures are classified into focal and generalized types. Around two-dozen AEDs are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbama-zepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate, parampanel). Carbamazepine, phenytoin, and valproate are the first-line agents for partial seizures and generalized tonic-clonic seizures. Ethosuximide is the drug of choice for absence seizures. AEDs are orally-active and show unique pharmacokinetic features. Some AEDs cause enzyme induction and hence produce drug-drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, and pregabalin do not cause enzyme induction. Despite many advances in epilepsy research, nearly 30% of people with epilepsy have drug-resistant or intractable seizures. Presently, there is no cure for epilepsy. Thus, newer and better AEDs that can better prevent refractory seizures and modify the disease are needed for curing epilepsy.  



Download data is not yet available.


Metrics Loading ...


Epilepsy, Seizure, Phenytoin, Carbamazepine, Valproate, Ethosuximide;, Levetiracetam




How to Cite

Reddy DS. Clinical Pharmacology of Modern Antiepileptic Drugs. Scopus Indexed [Internet]. 2017 Nov. 30 [cited 2024 Jun. 14];10(6):3875-90. Available from:


Arana A et al (2010). Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med 363: 542.
Berg ET, Berkovic SF and Brodie MJ (2010). Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 51: 676-685.
Biton V et al (2011). A randomized, double-blind, placebo-controlled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures. Epilepsia 52: 234.
Brodie MJ and Kwan P (2002). Staged approach to epilepsy management. Neurology 58(suppl 5): S2-S8.
Brodie MJ, Richens A and Yuen AW (1995). Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group. Lancet 345: 476-479.
Brophy, GM, Bel, R, Claassen J, Alldredge B, Bleck TP, Glauser T.;, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM and Vespa PM (2012). Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17: 3-23.
Cendes, F (2005). Progressive hippocampal and extra hippocampal atrophy in drug resistant epilepsy. Current Opinion in Neurology 18: 173-177.
Chadwick DW, Anhut H and Greiner MJ (1998). A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945-77. Neurology 51: 1282-1288.
Christensen J et al (2013). Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA; 309: 1696.
Clossen BL and Reddy DS (2017). Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy. Biochim Biophys Acta 1863: 1519-1538.
Delgado-Escueta AV, Wasterlain C, Treiman DM and Porter R.J. (1983). Status epilepticus: summary. Adv. Neurol. 34: 537-541.
DeLorenzo RJ, Towne AR, Pellock JM and Ko D (1992). Status epilepticus in children, adults, and the elderly. Epilepsia 33 (Suppl 4): S15-25.
Diaz RA, Sancho J and Serratosa J (2008). Antiepileptic drug interactions. Neurologist 14(S1): S55-S65.
Dudek FE and Staley KJ (2011). The time course of acquired epilepsy: implications for therapeutic intervention to suppress epileptogenesis. Neurosci Lett 497: 240-246.
Duncan JS, Sander JW, Sisodiya SM and Walker MC (2006). Adult epilepsy. Lancet 367(9516): 1087-1100.
Engel J Jr (1993). Clinical neurophysiology, neuroimaging, and the surgical treatment of epilepsy. Curr. Opin. Neurol. Neurosurg 6(2): 240-249.
French JA and Pedley TA (2008). Clinical practice. Initial management of epilepsy. N Engl J Med. 359(2): 166-76.
French JA et al (2012a). Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 79: 589.
French JA et al (2012b). Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia 2012 Aug 20 (epub).
French JA et al (2016). Adjunctive pregabalin vs gabapentin for focal seizures. Neurology 87: 1242.
French JA, Kanner AM, Bautista MD, et al (2004). Efficacy and tolerability of the new antiepileptic drugs. I: Treatment of new onset epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 62: 1252-1260.
Glauser TA et al (2010). Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 362: 790.
Gluaser T, Ben-Menachem E, Bourgeois B, et al (2006). ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 47: 1094-1120.
Harden CL et al (2009). Practice parameter update: management issues for women with epilepsy–focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 3: 133.
Harden CL et al. (2009). Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): part I, II, and III. Epilepsia 50(5): 1229-36 (part I), 1237-46 (part II), 1247-55 (part III).
Hernández-Diaz S et al (2012). Comparative safety of antiepileptic drugs during pregnancy. Neurology 78: 1692.
Hesdorffer DC, Beck V et al. (2013). Research implications of the Institute of Medicine Report, Epilepsy Across the Spectrum: Promoting Health and Understanding. Epilepsia 54: 207-216.
ILAE (1981). Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22: 489-501.
Jacobs MP, Leblanc, GG et al (2009). Curing epilepsy: progress and future directions. Epilepsy Behav 14: 438-445.
Jentink J et al (2010). Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 362: 2185.
Kesselheim AS et al (2010). Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs 70: 605.
Kesselheim AS et al (2013). Variations in pill appearance of antiepileptic drugs and the risk of nonadherence. JAMA Intern Med 173: 202.
Kluger G et al (2010). Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study. Acta Neurol Scand 122: 202.
Köhling R and Staley K (2011). Network mechanisms for fast ripple activity in epileptic tissue. Epilepsy Res 97: 318-323.
Kwan P et al (2014). Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia 55: 38.
Lowenstein DH (2012). Seizures and epilepsy. In: Fauci AS, Kasper DL, Jameson JL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: The McGraw Hill Companies.
Mani R, Pollard J and Dichter MA (2011). Human clinical trails in antiepileptogenesis. Neurosci Lett 497: 251-256.
Marson AG, Al-Kharusi AM, Alwaidh M, et al (2007a). The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblended randomised controlled trial. Lancet 369: 1000-1015.
Marson AG, Al-Kharusi AM, Alwaidh M, et al (2007b). The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: An unblinded randomised controlled trial. Lancet 369: 1016-1026.
Mattson RH, Cramer JA, Collins JF, et al (1985). Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 313: 145-151.
Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ and Fitzsimmons BF (2002). Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 59(2): 205-210.
McNamara JO (2006). Pharmacotherapy of the epilepsies. In gmgm pharmacological basis of therapeutics, 11th edition. Brunton LL, Lazo, JS, Parker KL, eds. McGraw Hill: 501-525.
Meador KJ (2006). Cognitive and memory effects of new antiepileptic drugs. Epilepsy Res 68: 63-67.
Meador KJ et al (2012). Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology 78: 1207.
Mølgaard-Nielsen D and Hviid A (2011). Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 305: 1996.
Montouris GD et al (2014). The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome. Eplepsia 55 (suppl 4): 10.
O’Dell C et al (2005). Rectal diazepam gel in the home management of seizures in children. Pediatr Neurol 33: 166.
Patorno E et al (2010). Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA 303: 1401.
Patsalos PN, Berry DJ, Bourgeois BF, et al (2008). Antiepileptic drugs—best practice guideline for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 49: 1239-1276.
Pennel PB (2008). Antiepileptic drugs during pregnancy: What is known and which AEDs seem to be safest? Epilepsia 49 (Suppl. 9): 43-55.
Pitkänen A. and Lukasiuk K (2011). Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol 10: 173-186.
Privitera MD et al (2016). Generic-to-generic lamotrigine switches in people with epilepsy: the randomized controlled EQUIGEN trial. Lancet Neurol 15: 365.
Rao M.S., Hattiangady B., Reddy D.S. and Shetty A.K. (2006). Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy. J Neurosci Res 83: 1088-1105.
Reddy D.S. (2009). The role of neurosteroids in the pathophysiology and treatment of catamenial epilepsy. Epilepsy Res 85: 1-30.
Reddy D.S. (2011). Role of anticonvulsant and antiepileptogenic neurosteroids in the pathophysiology and treatment of epilepsy. Front Endocrinol 2 (article 38): 1-18.
Reddy DS (2010). Clinical pharmacokinetic interactions between antiepileptic drugs and hormonal contraceptives. Exp Rev Clin Pharmacol 3(3): 1-10.
Reddy DS (2013). Role of hormones and neurosteroids in epileptogenesis. Frontiers in Cellular Neuroscience 7(article 115): 1-20.
Reddy DS (2017). Do oral contraceptives increase epileptic seizures? Expert Rev Neurother 17(2): 129-134.
Reddy DS and Kuruba R (2013). Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int J Mol Sci 14: 18284-18318.
Reddy DS and Mohan A (2011). Development and persistence of limbic epileptogenesis are impaired in mice lacking progesterone receptors. J Neurosci 31: 650-658.
Reddy DS and Volkmer R 2nd (2017). Neurocysticercosis as an infectious acquired epilepsy worldwide. Seizure 52: 176-181.
Rogawski MA and Löscher W (2004). The neurobiology of antiepileptic drugs. Nature Rev Neuroscience 5: 553-64.
Rogers SJ and Cavazos JE (2005). In: Talbert RL, DiPiro JT, Matzke GR, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: The McGraw Hill Companies; Epilepsy.
Saetre E et al (2010). Antiepileptic drugs and quality of life in the elderly: results from a randomized double-blind trial of carbamazepine and lamotrigine in patients with onset of epilepsy in old age. Epilepsy Behav 17: 395.
Schachter SC (2007). Curently available antiepileptic drugs. Neurotherapeutics 4: 4-11.
Shorvon SD et al (2017). Eslicarbazepine acetate: its effectiveness as adjunctive therapy in clinical trials and open studies. J Neurol 2017 Jan 18 (epub).
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W, et al (2012). Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 366: 591-600.
Silbergleit R, Lowenstein D, Durkalski V, et al. RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics. Epilepsia 2011;52 (Suppl. 8): S45–S47. Stafstrom CE, Zupec-Kania B and Rho JM (2008). Ketogenic diet and related dietary treatments. Epilepsia 49 (Suppl. 8.): 1-2.
Stecker MM, Kramer TH, Raps EC, O'Meeghan R, Dulaney E and Skaar DJ (1998). Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 39: 18-26.
Stringer JL (1998). Drugs for Seizure Disorders. In Human Pharmacology: Molecular to Clinical, 3rd edition. TM Brody, J Larner, KP Minneman, eds. Mosby-Year Book, Epilepsies: 373-383.
Sutula TP (2004). Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development. Epilepsy Re 60: 161-171.
Temkin NR (2001). Antiepileptogenesis and seizure prevention trials with antiepileptic drugs, meta-analysis of controlled trials. Epilepsia 42: 515-524.
Tomson T, Perucca E and Battino D (2004). Navigating toward fetal and maternal health: The challenge of treating epilepsy in pregnancy. Epilepsia 45: 1171-1175.
Vining EP (2010). Ethosuximide in childhood absence epilepsy older and better. N Engl J Med 362: 843.
Vivas AC, Baaj AA, Benbadis SR and Vale FL (2012). The health care burden of patients with epilepsy in the United States: An analysis of a nationwide database over 15 years. Neurosurg Focus 32: E1.
Wheless JW and Treiman DM (2008). The role of the newer antiepileptic drugs in the treatment of generalized convulsive status epilepticus. Epilepsia 49(Suppl 9): 74-78.
Younus I, Reddy DS (2017a). Epigenetic interventions for epileptogenesis: A new frontier for curing epilepsy. Pharmacol Ther 177:108-122.
Younus I and Reddy DS (2017b). A resurging boom in new drugs for epilepsy and brain disorders. Expert Rev Clin Pharmacol 23: 1-19.

Most read articles by the same author(s)

1 2 > >>