What is the role of pregabalin in the treatment of epilepsy?

Answer

Pregabalin is an analogue of the neurotransmitter GABA and has analgesic, anticonvulsant, and anxiolytic effects.^{[50, 51]}Despite being a GABA analogue, pregabalin is inactive at GABA receptors, including GABA-A, benzodiazepine, t-butylbicyclophosphorothionate (TBPS), and GABA-B radioligand binding sites.^[52]Neither pregabalin nor GBP alters GABA concentration in brain tissues^[53]or inhibits GABA transport in vitro. Pregabalin binds with high affinity to both the alpha₂ delta-1 and alpha₂ delta-2 subtypes.^[54]

GBP and pregabalin binding to the alpha₂ delta protein are proposed to mediate the functional effects these molecules have on calcium currents in activated neurons and on stimulated neurotransmitter release.^[55]The effect is a reduced release of excitatory neurotransmitters and peptide neuromodulators under membrane hyperexcitability, which is postulated to mediate the analgesic, anxiolytic, and anticonvulsant effect.^[56]

Pregabalin is active in several animal models of seizures. In the high-intensity electroshock test, pregabalin inhibited tonic extensor seizures in rats and low-intensity electroshock seizures in mice. In the DBA/2 audiogenic mouse model and clonic seizures, pregabalin prevented tonic extensor seizures from pentylenetetrazole in mice. In a kindled rat model of partial seizures, pregabalin prevented stages 4–5 behavioral seizures. However, pregabalin was not effective in models of absence seizures.^[57]

Pregabalin is well absorbed after oral administration. When the drug has been given orally under fasting conditions, the peak plasma concentration is 1.5 hours; however, when it is given with food, the rate of pregabalin absorption is decreased, resulting in a decrease in peak plasma concentration of approximately 25-30% and an increase in time to peak plasma concentration (T_max) to approximately 3 hours. Oral bioavailability is 90% and it is independent of dose and presence of food. Steady state is achieved within 24-48 hours.

Pregabalin does not bind to plasma proteins. The apparent volume of distribution after oral administration is approximately 0.5 L/kg. Pregabalin crosses the blood-brain barrier in animals and has been shown to cross the placenta in rats and is present in the milk of lactating rats.

After oral administration, approximately 90% is recovered in the urine as unchanged pregabalin. Only about 0.9% is found in urine as the N -methylated derivative.

Pregabalin is eliminated primarily by renal excretion, with a mean elimination half-life of 6.3 hours in patients with normal renal function. Pregabalin elimination is nearly proportional to creatinine clearance (CrCl). Dosage reduction in patients with renal failure is necessary. Pregabalin is effectively removed from plasma by hemodialysis (50% after 4 h of hemodialysis).

Pregabalin has no pharmacokinetic drug interactions.

Pregabalin is indicated as adjunctive therapy for partial-onset seizures in adults and children aged 1 month or older. Efficacy as add-on therapy for partial epilepsy has been demonstrated in four major trials.^{[58, 59, 60, 61]}Patients given pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency. Subgroup analyses assessing the effect of individual doses of 50 mg pregabalin was not effective.^[62]

Pregabalin’s lack of drug interactions, lack of plasma protein binding, and renal excretion make it particularly useful in patients with renal or hepatic disease and in patients on complex drug regimens. Patients with coexisting migraine headache or neuropathic pain may benefit from this drug.

Pregabalin is relatively well tolerated, although it does have some adverse effects, particularly in high doses. No significant serious idiosyncratic or systemic adverse effects have been reported.

The most common side effects of pregabalin are dizziness and drowsiness. Other important side effects include dry mouth, edema, blurred vision, weight gain, and difficulty concentrating. Pregabalin has rarely been associated with angioedema (swelling of the face, tongue, lips, and gums, throat, and larynx).

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Molgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA. 2011 May 18. 305(19):1996-2002. [Medline].
Costa J, Fareleira F, Ascencao R, et al. Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy: A systematic review and meta-analysis. Epilepsia. 2011 Jul. 52(7):1280-91. [Medline].
Birbeck GL, French JA, Perucca E, Simpson DM, Fraimow H, George JM, et al. Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy. Neurology. 2012 Jan 10. 78(2):139-45. [Medline].
Xu T, Bajjalieh SM. SV2 modulates the size of the readily releasable pool of secretory vesicles. Nat Cell Biol. 2001 Aug. 3(8):691-8. [Medline].
Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, et al. Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci U S A. 1999 Dec 21. 96(26):15268-73. [Medline]. [Full Text].
Janz R, Goda Y, Geppert M, Missler M, Südhof TC. SV2A and SV2B function as redundant Ca2+ regulators in neurotransmitter release. Neuron. 1999 Dec. 24(4):1003-16. [Medline].
Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004 Jun 29. 101(26):9861-6. [Medline]. [Full Text].
Noyer M, Gillard M, Matagne A, Hénichart JP, Wülfert E. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol. 1995 Nov 14. 286(2):137-46. [Medline].
Beydoun A, Sachdeo RC, Rosenfeld WE, Krauss GL, Sessler N, Mesenbrink P, et al. Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial. Neurology. 2000 Jun 27. 54(12):2245-51. [Medline].
Gelisse P, Genton P, Kuate C, Pesenti A, Baldy-Moulinier M, Crespel A. Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized epilepsies. Epilepsia. 2004 Oct. 45(10):1282-6. [Medline].
Schachter SC, Vazquez B, Fisher RS, Laxer KD, Montouris GD, Combs-Cantrell DT, et al. Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures. Neurology. 1999 Mar 10. 52(4):732-7. [Medline].
Tecoma ES. Oxcarbazepine. Epilepsia. 1999. 40 Suppl 5:S37-46. [Medline].
Cunnington MC. The International Lamotrigine pregnancy registry update for the epilepsy foundation. Epilepsia. 2004 Nov. 45(11):1468. [Medline].
Matsuo F. Lamotrigine. Epilepsia. 1999. 40 Suppl 5:S30-6. [Medline].
Matsuo F, Bergen D, Faught E, Messenheimer JA, Dren AT, Rudd GD, et al. Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures. U.S. Lamotrigine Protocol 0.5 Clinical Trial Group. Neurology. 1993 Nov. 43(11):2284-91. [Medline].
Meador KJ, Penovich P. What is the risk of orofacial clefts from lamotrigine exposure during pregnancy?. Neurology. 2008 Sep 2. 71(10):706-7. [Medline].
Brodie MJ, Duncan R, Vespignani H, Solyom A, Bitenskyy V, Lucas C. Dose-dependent safety and efficacy of zonisamide: a randomized, double-blind, placebo-controlled study in patients with refractory partial seizures. Epilepsia. 2005 Jan. 46(1):31-41. [Medline].
Chadwick D. Zonisamide: Chemistry, Mechanism of Action, and Pharmacokinetics. NJ: Clinicians Group; 2001.
Kothare SV, Valencia I, Khurana DS, Hardison H, Melvin JJ, Legido A. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Disord. 2004 Dec. 6(4):267-70. [Medline].
Kyllerman M, Ben-Menachem E. Zonisamide for progressive myoclonus epilepsy: long-term observations in seven patients. Epilepsy Res. 1998 Jan. 29(2):109-14. [Medline].
Leppik I. Zonisamide Chemistry, Mechanism of Action, and Pharmacokinetics. NJ: Clinicians Group; 2001. 3-5.
Leppik IE. Zonisamide. Epilepsia. 1999. 40 Suppl 5:S23-9. [Medline].
Masakazu S. Zonisamide Chemistry, Mechanism of Action, and Pharmacokinetics. NJ: Clinicians Group; 2001. 10-11.
Morrell M. Women’s Issues and the Use of Zonisamide. NJ: Clinicians Group; 2001. 3-5.
Rogawski MA. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res. 2006 Jun. 69(3):273-94. [Medline].
Errington AC, Stöhr T, Heers C, Lees G. The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol Pharmacol. 2008 Jan. 73(1):157-69. [Medline].
Curia G, Biagini G, Perucca E, Avoli M. Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009. 23(7):555-68. [Medline].
Errington AC, Coyne L, Stöhr T, Selve N, Lees G. Seeking a mechanism of action for the novel anticonvulsant lacosamide. Neuropharmacology. 2006 Jun. 50(8):1016-29. [Medline].
Doty P, Rudd GD, Stoehr T, Thomas D. Lacosamide. Neurotherapeutics. 2007 Jan. 4(1):145-8. [Medline].
Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007 Jul. 48(7):1308-17. [Medline].
Halász P, Kälviäinen R, Mazurkiewicz-Beldzinska M, Rosenow F, Doty P, Hebert D, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. Epilepsia. 2009 Mar. 50(3):443-53. [Medline].
Chung S, Sperling MR, Biton V, Krauss G, Hebert D, Rudd GD, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010 Jun. 51(6):958-67. [Medline].
Guilhoto LM, Loddenkemper T, Gooty VD, Rotenberg A, Takeoka M, Duffy FH, et al. Experience with lacosamide in a series of children with drug-resistant focal epilepsy. Pediatr Neurol. 2011 Jun. 44(6):414-9. [Medline].
Heyman E, Lahat E, Levin N, Berkovitch M, Gandelman-Marton R. Preliminary efficacy and safety of lacosamide in children with refractory epilepsy. Eur J Paediatr Neurol. 2012 Jan. 16(1):15-9. [Medline].
Afra P, Adamolekun B. Lacosamide treatment of juvenile myoclonic epilepsy. Seizure. 2012 Apr. 21(3):202-4. [Medline].
Mnatsakanyan L, Chung JM, Tsimerinov EI, Eliashiv DS. Intravenous Lacosamide in refractory nonconvulsive status epilepticus. Seizure. 2012 Apr. 21(3):198-201. [Medline].
Cherry S, Judd L, Muniz JC, Elzawahry H, LaRoche S. Safety and efficacy of lacosamide in the intensive care unit. Neurocrit Care. 2012 Apr. 16(2):294-8. [Medline].
Krauss GL, Klein P, Brandt C, Lee SK, Milanov I, Milovanovic M, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2019 Nov 13. [Medline].
Xcopri (cenobamate) [package insert]. Paramus, NJ: SK Life Science, Inc. November 2019. Available at [Full Text].
Sequeira DJ, Van Ess PJ, Braun TL et al. Efficacy of Nayzilam (USL261; midazolam nasal spray) in subjects with acute repetitive seizures: Results from the randomized, phase 3 ARTEMIS-1 clinical trial (Abst 3.269). Presented at the American Epilepsy Society 2017 Annual Meeting. Washington, D.C. December 1-5, 2017.
Valtoco (diazepam intranasal) [package insert]. San Diego, CA: Neurelis, Inc. January 2020. Available at [Full Text].
Sperling M, Hogan R, Biton V, Tarquinio D, Carrazana E. A 12-month, open-label, repeat-dose safety study of Valtoco (NRL-1, diazepam nasal spray) in patients with epilepsy: interim report (P1.5-028). Neurology. 2019 Apr 09; 92(15 suppl). [Full Text].
Aicardi J, Mumford JP, Dumas C, Wood S. Vigabatrin as initial therapy for infantile spasms: a European retrospective survey. Sabril IS Investigator and Peer Review Groups. Epilepsia. 1996 Jul. 37(7):638-42. [Medline].
Malmgren K, Ben-Menachem E, Frisén L. Vigabatrin visual toxicity: evolution and dose dependence. Epilepsia. 2001 May. 42(5):609-15. [Medline].
Spence SJ, Sankar R. Visual field defects and other ophthalmological disturbances associated with vigabatrin. Drug Saf. 2001. 24(5):385-404. [Medline].
Thomas L, Trimble M, Schmitz B, Ring H. Vigabatrin and behaviour disorders: a retrospective survey. Epilepsy Res. 1996 Sep. 25(1):21-7. [Medline].
Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998 Dec 2. 280(21):1831-6. [Medline].
Kondo T, Fromm GH, Schmidt B. Comparison of gabapentin with other antiepileptic and GABAergic drugs. Epilepsy Res. 1991 Apr. 8(3):226-31. [Medline].
Petroff OA, Hyder F, Rothman DL, Mattson RH. Effects of gabapentin on brain GABA, homocarnosine, and pyrrolidinone in epilepsy patients. Epilepsia. 2000 Jun. 41(6):675-80. [Medline].
Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004. 45 Suppl 6:13-8. [Medline].
Brodie MJ. Pregabalin as adjunctive therapy for partial seizures. Epilepsia. 2004. 45 Suppl 6:19-27. [Medline].
Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007 Feb. 73(2):137-50. [Medline].
Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure. 2003 Jul. 12(5):300-6. [Medline].
Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR. Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit. Mol Pharmacol. 2002 Sep. 62(3):485-96. [Medline].
Dooley DJ, Donovan CM, Pugsley TA. Stimulus-dependent modulation of [(3)H]norepinephrine release from rat neocortical slices by gabapentin and pregabalin. J Pharmacol Exp Ther. 2000 Dec. 295(3):1086-93. [Medline].
Bryans JS, Davies N, Gee NS, Dissanayake VU, Ratcliffe GS, Horwell DC, et al. Identification of novel ligands for the gabapentin binding site on the alpha2delta subunit of a calcium channel and their evaluation as anticonvulsant agents. J Med Chem. 1998 May 21. 41(11):1838-45. [Medline].
Vartanian MG, Radulovic LL, Kinsora JJ, Serpa KA, Vergnes M, Bertram E, et al. Activity profile of pregabalin in rodent models of epilepsy and ataxia. Epilepsy Res. 2006 Mar. 68(3):189-205. [Medline].
French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003 May 27. 60(10):1631-7. [Medline].
Arroyo S, Anhut H, Kugler AR, Lee CM, Knapp LE, Garofalo EA, et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Epilepsia. 2004 Jan. 45(1):20-7. [Medline].
Beydoun A, Uthman BM, Kugler AR, Greiner MJ, Knapp LE, Garofalo EA. Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology. 2005 Feb 8. 64(3):475-80. [Medline].
Elger CE, Brodie MJ, Anhut H, Lee CM, Barrett JA. Pregabalin add-on treatment in patients with partial seizures: a novel evaluation of flexible-dose and fixed-dose treatment in a double-blind, placebo-controlled study. Epilepsia. 2005 Dec. 46(12):1926-36. [Medline].
Lozsadi D, Hemming K, Marson AG. Pregabalin add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2008 Jan 23. CD005612. [Medline].
Cramer JA, Mattson RH, Bennett DM, Swick CT. Variable free and total valproic acid concentrations in sole- and multi-drug therapy. Ther Drug Monit. 1986. 8(4):411-5. [Medline].
Taverna S, Mantegazza M, Franceschetti S, Avanzini G. Valproate selectively reduces the persistent fraction of Na+ current in neocortical neurons. Epilepsy Res. 1998 Sep. 32(1-2):304-8. [Medline].
Vreugdenhil M, Wadman WJ. Modulation of sodium currents in rat CA1 neurons by carbamazepine and valproate after kindling epileptogenesis. Epilepsia. 1999 Nov. 40(11):1512-22. [Medline].
Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med. 2009 Apr 16. 360(16):1597-605. [Medline]. [Full Text].
Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013 Mar. 12(3):244-52. [Medline].
Pellock JM, Brodie MJ. Felbamate: 1997 update. Epilepsia. 1997 Dec. 38(12):1261-4. [Medline].
Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors. Ann Neurol. 1994 Feb. 35(2):229-34. [Medline].
Wasterlain CG, Adams LM, Wichmann JK, Sofia RD. Felbamate protects CA1 neurons from apoptosis in a gerbil model of global ischemia. Stroke. 1996 Jul. 27(7):1236-40. [Medline].
Wallis RA, Panizzon KL. Glycine reversal of felbamate hypoxia protection. Neuroreport. 1993. 4(7):951-4.
Wasterlain CG, Adams LM, Schwartz PH, Hattori H, Sofia RD, Wichmann JK. Posthypoxic treatment with felbamate is neuroprotective in a rat model of hypoxia-ischemia. Neurology. 1993 Nov. 43(11):2303-10. [Medline].
Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS. Presumed topiramate-induced bilateral acute angle-closure glaucoma. Am J Ophthalmol. 2001 Jul. 132(1):112-4. [Medline].
Glauser TA, Levisohn PM, Ritter F, Sachdeo RC. Topiramate in Lennox-Gastaut syndrome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia. 2000. 41 Suppl 1:S86-90. [Medline].
Ochoa JG. Pruritus, a rare but troublesome side effect of topiramate. Epilepsia. 2000. 41(supp 7):
Privitera M, Fincham R, Penry J, Reife R, Kramer L, Pledger G, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group. Neurology. 1996 Jun. 46(6):1678-83. [Medline].
Sankar PS, Pasquale LR, Grosskreutz CL. Uveal effusion and secondary angle-closure glaucoma associated with topiramate use. Arch Ophthalmol. 2001 Aug. 119(8):1210-1. [Medline].
Shank RP, Gardocki JF, Vaught JL, Davis CB, Schupsky JJ, Raffa RB, et al. Topiramate: preclinical evaluation of structurally novel anticonvulsant. Epilepsia. 1994 Mar-Apr. 35(2):450-60. [Medline].
Zona C, Ciotti MT, Avoli M. Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neurosci Lett. 1997 Aug 15. 231(3):123-6. [Medline].
Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology. May 1 2012. 78:1408-15. [Medline].
French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. Aug 7. 79:589-96. [Medline].
French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of randomized global phase III study 305. Epilepsia. 2012 Aug 20. 53:[Medline].
Fycompa (perampanel) [package insert]. Woodcliff Lake, NJ: Eisai Inc. June 2015. Available at [Full Text].
Fycompa (perampanel) [package insert]. Woodcliff Lake, NJ: Eisai Inc. October 2012. Available at [Full Text].
Cataldi M, Lariccia V, Secondo A, di Renzo G, Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005 May. 313(2):720-30. [Medline].
Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000 Jul 25. 55(2):236-42. [Medline].
Gower AJ, Hirsch E, Boehrer A, Noyer M, Marescaux C. Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy. Epilepsy Res. 1995 Nov. 22(3):207-13. [Medline].
Loscher W, Hönack D, Rundfeldt C. Antiepileptogenic effects of the novel anticonvulsant levetiracetam (ucb L059) in the kindling model of temporal lobe epilepsy. J Pharmacol Exp Ther. 1998 Feb. 284(2):474-9. [Medline].
Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000 Feb. 85(2):77-85. [Medline].
Privitera M. Efficacy of levetiracetam: a review of three pivotal clinical trials. Epilepsia. 2001. 42 Suppl 4:31-5. [Medline].
Shorvon SD, Löwenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. European Levetiracetam Study Group. Epilepsia. 2000 Sep. 41(9):1179-86. [Medline].
Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015 Dec. 56 (12):1890-1898. [Medline].
Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. N Engl J Med. 2018 May 17. 378 (20):1888-1897. [Medline].
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018 Mar 17. 391 (10125):1085-1096. [Medline].
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25. 376 (21):2011-2020. [Medline].
Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP, UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017 Aug 6. [Medline].
Anderson P. Cannabidiol Reduces Seizures in Various Epilepsy Disorders. Medscape News & Perspective. Available at http://www.medscape.com/viewarticle/872763#vp_3. December 05, 2016; Accessed: August 25, 2017.
Diacomit (stiripentol) [package insert]. France: Biocodex. August, 2018. Available at [Full Text].
Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, et al. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16. 75(20):1817-24. [Medline].
Luszczki JJ. Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr. 61(2):197-216. [Medline].

Media Gallery

Pearls of antiepileptic drug use and management.
Dynamic target of seizure control in management of epilepsy is achieving balance between factors that influence excitatory postsynaptic potential (EPSP) and those that influence inhibitory postsynaptic potential (IPSP).
Antiepileptic drugs can be grouped according to their major mechanism of action. Some antiepileptic drugs work by acting on combination of channels or through some unknown mechanism of action.
Some antiepileptic drugs stabilize inactive configuration of sodium (Na+) channel, preventing high-frequency neuronal firing.
Low-voltage calcium (Ca2+) currents (T-type) are responsible for rhythmic thalamocortical spike and wave patterns of generalized absence seizures. Some antiepileptic drugs lock these channels, inhibiting underlying slow depolarizations necessary to generate spike-wave bursts.
Gamma-aminobutyric acid (GABA)-A receptor mediates chloride (Cl-) influx, leading to hyperpolarization of cell and inhibition. Antiepileptic drugs may act to enhance Cl- influx or decrease GABA metabolism.
Glutamate (main excitatory neurotransmitter in central nervous system) binds to multiple receptor sites that differ in activation and inactivation time courses, desensitization kinetics, conductance, and ion permeability. Three main glutamate receptor subtypes are N-methyl-D-aspartate (NMDA), metabotropic, and non-NMDA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA] and kainate receptors). Antiepileptic drugs known to possess this mechanism of action are listed.
Schematic representation of N-methyl-D-aspartate (NMDA) receptor.
GABA drugs and their known sites of action.

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Author

Juan G Ochoa, MD Associate Professor of Neurology, Director of USA SouthCEP, The Comprehensive Epilepsy Program, Residency Program Director, University of South Alabama College of Medicine

Juan G Ochoa, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Nothing to disclose.

Coauthor(s)

Willise Riche, MD

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES Professor with Tenure, Departments of Neurology, Neuroscience, and Physiology, Assistant Dean for the MD/PhD Program, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Neurological Association, Society for Neuroscience

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Brain Sentinel, consultant.<br/>Stakeholder (<5%), Co-founder for: Brain Sentinel.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Ceribell, Eisai, Greenwich, Growhealthy, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Serve(d) as a speaker or a member of a speakers bureau for: Eisai, Greenwich, LivaNova, Sunovion<br/>Received research grant from: Cavion, LivaNova, Greenwich, Sunovion, SK biopharmaceuticals, Takeda, UCB.

Additional Contributors

Erasmo A Passaro, MD, FAAN Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Health System, Florida Center for Neurology

Erasmo A Passaro, MD, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, American Society of Neuroimaging

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: UCB; Sunovion; Eisai, GWPharma.

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