Epilepsy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:

overview

Medical Therapy

Pharmacologic medical therapies for epilepsy is anti-seizure drugs such as:

  • Drugs that affect voltage-dependent Na+ channels
    • Carbamazepin:
      • It can be used in treatment of both generalized and focal epilepsy.
      • The initial dose is 2-3 mg/kg per day divided into at least two time.
      • The maximum dosing is 10 mg/kg three-times-daily.
      • The most common side effects of this drug are GI disturbance, rash, hyponatremia and fluid retention.[1] [2]
    • Eslicarbazepin
      • It can be used for treatment of focal-onset seizures in adult and children under 4 y/o.[3]
      • The initial dosage is 400 mg/daily for adults.
      • The maximum dosing is maintenance dose of 800 mg/daily.[4]
      • The most common side effects of this drug are dizziness, drowsiness, nausea, headache, fatigue, vertigo, ataxia, diplopia, blurred vision, and tremor.[5]
    • Lacosamide
      • It can be used for treatment of focal-onset seizures in adult and children older than 4 y/o.[6]
      • The initial dosage is 50 mg twice/daily as adjunctive therapy in adults and 100 mg twice per day as monotherapy .
      • The maximum dosage is 200 to 400 mg per day. Children should be dosed according to body weight.[7]
      • The most common side effects are Dizziness, nausea, vertigo, and ataxia.[8]
    • Lamotrigine
      • It can be used for adjunctive treatment for primary generalized tonic-clonic seizures and focal seizures in adults and children under two y/o.[9]
      • The initial dosage is 25 mg/daily.
      • The maximum dosage is 225 to 375 mg/daily[10]
      • The most common side effects are rash and nausea.[11]
    • Oxcarbazepine
      • It can be used for treatment of focal and secondarily generalized tonic-clonic seizures.[12]
      • The initial dosage is 300 to 600 mg/day.
      • The maximum dosage is 900 to 3000 mg/day.[13]
      • The most common side effects are hyponatremia, sedation, headache, rash, dizziness, vertigo, ataxia, nausea, and diplopia.[14]
    • Phenytoin
      • It can be used for treatment of focal/generalized seizures and status epilepticus.[15]
      • The initial dosage is 15 mg/kg/day in three doses.[16]
      • The most common side effects are gingival hypertrophy, hirsutism, rash, folic acid depletion, and decreased bone density.[17]
    • Rufinamide
      • It can be used for adjunctive treatment of seizures associated with Lennos-gastaut syndrome (LGS).[18]
      • The initial dosage In children is 10 mg/kg per day in two divided doses and in adults is 400 to 800 mg per day in two divided doses.
      • The maximum dosage in children is 45 mg/kg per day or 3200 mg/day and in adults is 3200 mg/day.[19]
      • The most common side effects are drowsiness and vomiting.[20]
    • Zonisamide
      • It can be used for treatment of focal and generalized seizures in both adults and children.[21]
      • The initial dosage is 100 to 200 mg/daily in two divided doses.
      • The maximum dosage is 400 to 600 mg/daily.[22]
      • The most common side effects are drowsiness, anxiety, ataxia, anorexia, confusion, abnormal thinking, fatigue, dizziness and decreased sweating and fever in children. [23]
  • Drugs that affect Ca currents
    • Ethosuximide
      • It can be used for treatment of absence seizures.
      • The initial dosage is 20 to 40 mg/kg/day.
      • The maximum serum level is 40 to 100 mcg/mL (280 to 700 micromol/L).
      • The most common side effects are nausea and vomiting, sleep disorders and somnolence.[24]
  • Drugs that affect GABA activity
    • Benzodiazepines
      • It can be used for adjunctive therapy for myoclonic/atonic seizures and focal/generalized tonic-clonic seizures.
      • The most common side effects are anterograde amnesia, drowsiness and increased risk of falling in elderly persons.[25]
    • Phenobarbital
      • It can be used for treatment of generalized and focal seizures.
      • The initial dosage is 1 to 5 mg/kg per day.
      • The goal therapeutic level is 10 to 40 mcg/mL (43 to 172 micromol/L).[26]
      • The most common side effects are sleep disturbance and daytime irritability.[27]
    • Tiagabine
      • It can be used for adjunctive treatment for focal seizures.[28]
      • The initial dosage is 4 to 8 mg/day.
      • The most common side effects are dizziness, somnolence, anxiety, tremor, difficulty concentrating, nausea and abdominal pain.[29]
    • Vigabatrin
      • It can be used for add-on treatment for refractory focal seizures.[30]
      • The initial dosage is 500 mg/day.
      • The maximum dosage is 3 gr/day.[31]
      • The most common side effects are visual loss, drowsiness, fatigue, headache, and dizziness.[32]
  • Drugs that affect glutamate receptor
    • Perampanel
      • It can be used for treatment of focal-onset seizures in patients older than 12 y/o and as adjunctive treatment for primary generalized tonic-clonic seizures.[33]
      • The initial dosage is 2 mg/day.
      • The maximum dose is 12 mg/day.[34]
      • The most common side effects are dizziness, drowsiness, headache, fatigue, irritability, ataxia, nausea, and weight gain.[35]
  • Drugs with multiple mechanisms of action
    • Felbamate
      • It can be used for treatment of focal seizures and Lennox-Gastaut syndrome (LGS).[36]
      • This drug can cause fatal aplastic anemia and hepatic failure.[37]
    • Topiramate
      • It can be used for treatment of focal seizures in adults and children older than two y/o.[38]
      • The initial dosage is 50 mg/day.[39]
      • The most common side effects are Weight loss, paresthesias, drowsiness, dizziness, depression, headache, cognition and language impairment.[40]
    • Valporate
      • It can be used for treatment of generalized and focal seizures.
      • The initial dosage is 10 to 15 mg/kg per day.[41]
      • The most common side effects are nausea, vomiting, hair loss, easy bruising, ]tremor, weight gain, obesity, insulin resistance, metabolic syndrome, thrombocytopenia and other coagulation disturbances, subclinical hypothyroidism, polycystic ovarian syndrome, fanconi syndrome.[42][43][44][45][46]
  • Drugs with other mechanisms of action
    • Brivaracetam
      • It can be used for treatment of focal-onset seizures and generalized epilepsy.[47][48]
      • The initial dosage is 50 mg twice daily.[49]
      • The most common side effects are irritability, anxiety, insomnia and depression.[50]
    • Gabapentin
      • It can be used for treatment of
      • The initial dosage is
      • The most common side effects are
    • Levetiracetam
      • It can be used for treatment of
      • The initial dosage is
      • The most common side effects are
    • Pregabalin
      • It can be used for treatment of
      • The initial dosage is
      • The most common side effects are

References

  1. ↑ Hirsch LJ, Arif H, Nahm EA, Buchsbaum R, Resor SR, Bazil CW (November 2008). "Cross-sensitivity of skin rashes with antiepileptic drug use". Neurology. 71 (19): 1527–34. doi:10.1212/01.wnl.0000334295.50403.4c. PMID 18981374.
  2. ↑ Cereghino JJ, Brock JT, Van Meter JC, Penry JK, Smith LD, White BG (May 1974). "Carbamazepine for epilepsy. A controlled prospective evaluation". Neurology. 24 (5): 401–10. PMID 4207990.
  3. ↑ Chang XC, Yuan H, Wang Y, Xu HQ, Hong WK, Zheng RY (October 2017). "Eslicarbazepine acetate add-on for drug-resistant partial epilepsy". Cochrane Database Syst Rev. 10: CD008907. doi:10.1002/14651858.CD008907.pub3. PMID 29067682.
  4. ↑ Almeida L, Minciu I, Nunes T, Butoianu N, Falcão A, Magureanu SA, Soares-da-Silva P (August 2008). "Pharmacokinetics, efficacy, and tolerability of eslicarbazepine acetate in children and adolescents with epilepsy". J Clin Pharmacol. 48 (8): 966–77. doi:10.1177/0091270008319706. PMID 18508949.
  5. ↑ Sperling MR, Abou-Khalil B, Harvey J, Rogin JB, Biraben A, Galimberti CA, Kowacs PA, Hong SB, Cheng H, Blum D, Nunes T, Soares-da-Silva P (February 2015). "Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial". Epilepsia. 56 (2): 244–53. doi:10.1111/epi.12894. PMC 4354260. PMID 25528898.
  6. ↑ Perucca E, Yasothan U, Clincke G, Kirkpatrick P (December 2008). "Lacosamide". Nat Rev Drug Discov. 7 (12): 973–4. doi:10.1038/nrd2764. PMID 19043448.
  7. ↑ Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD, Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, Rosenow F, Doty P, Hebert D, Sullivan T (July 2007). "Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures". Epilepsia. 48 (7): 1308–17. doi:10.1111/j.1528-1167.2007.01188.x. PMID 17635557.
  8. ↑ Perucca E, Yasothan U, Clincke G, Kirkpatrick P (December 2008). "Lacosamide". Nat Rev Drug Discov. 7 (12): 973–4. doi:10.1038/nrd2764. PMID 19043448.
  9. ↑ French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE, Sachdeo RC, Beydoun A, Glauser TA (April 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 (8): 1252–60. PMID 15111659.
  10. ↑ Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M, Straka T, Bazil CW, Adams DJ, Resor SR, Morrell MJ (September 2004). "Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy". Neurology. 63 (6): 1022–6. PMID 15452293.
  11. ↑ Hirsch LJ, Arif H, Nahm EA, Buchsbaum R, Resor SR, Bazil CW (November 2008). "Cross-sensitivity of skin rashes with antiepileptic drug use". Neurology. 71 (19): 1527–34. doi:10.1212/01.wnl.0000334295.50403.4c. PMID 18981374.
  12. ↑ Koch MW, Polman SK (October 2009). "Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures". Cochrane Database Syst Rev (4): CD006453. doi:10.1002/14651858.CD006453.pub2. PMID 19821367.
  13. ↑ Kim DW, Gu N, Jang IJ, Chu K, Yu KS, Cho JY, Yoon SH, Kim HS, Oh J, Lee SK (January 2012). "Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy". Epilepsia. 53 (1): e9–12. doi:10.1111/j.1528-1167.2011.03318.x. PMID 22091603.
  14. ↑ Buggy Y, Layton D, Fogg C, Shakir SA (May 2010). "Safety profile of oxcarbazepine: results from a prescription-event monitoring study". Epilepsia. 51 (5): 818–29. doi:10.1111/j.1528-1167.2009.02489.x. PMID 20132298.
  15. ↑ Yaari Y, Selzer ME, Pincus JH (August 1986). "Phenytoin: mechanisms of its anticonvulsant action". Ann. Neurol. 20 (2): 171–84. doi:10.1002/ana.410200202. PMID 2428283.
  16. ↑ Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, Klein TE, Callaghan JT (November 2014). "Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing". Clin. Pharmacol. Ther. 96 (5): 542–8. doi:10.1038/clpt.2014.159. PMID 25099164.
  17. ↑ Iivanainen M, Savolainen H (1983). "Side effects of phenobarbital and phenytoin during long-term treatment of epilepsy". Acta Neurol. Scand., Suppl. 97: 49–67. PMID 6424397.
  18. ↑ Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S (May 2008). "Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome". Neurology. 70 (21): 1950–8. doi:10.1212/01.wnl.0000303813.95800.0d. PMID 18401024.
  19. ↑ Marchand M, Fuseau E, Critchley DJ (February 2010). "Supporting the recommended paediatric dosing regimen for rufinamide in Lennox-Gastaut syndrome using clinical trial simulation". J Pharmacokinet Pharmacodyn. 37 (1): 99–118. doi:10.1007/s10928-009-9146-4. PMID 20084538.
  20. ↑ Wheless JW, Vazquez B (January 2010). "Rufinamide: a novel broad-spectrum antiepileptic drug". Epilepsy Curr. 10 (1): 1–6. doi:10.1111/j.1535-7511.2009.01336.x. PMC 2812713. PMID 20126329.
  21. ↑ Guerrini R, Rosati A, Segieth J, Pellacani S, Bradshaw K, Giorgi L (August 2013). "A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy". Epilepsia. 54 (8): 1473–80. doi:10.1111/epi.12233. PMID 23837461.
  22. ↑ Leppik IE (December 2004). "Zonisamide: chemistry, mechanism of action, and pharmacokinetics". Seizure. 13 Suppl 1: S5–9, discussion S10. doi:10.1016/j.seizure.2004.04.016. PMID 15511691.
  23. ↑ Park SP, Hwang YH, Lee HW, Suh CK, Kwon SH, Lee BI (January 2008). "Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients". Epilepsy Behav. 12 (1): 102–8. doi:10.1016/j.yebeh.2007.08.002. PMID 17945539.
  24. ↑ Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, Clark PO, Capparelli EV, Adamson PC (March 2010). "Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy". N. Engl. J. Med. 362 (9): 790–9. doi:10.1056/NEJMoa0902014. PMC 2924476. PMID 20200383.
  25. ↑ Uzun S, Kozumplik O, Jakovljević M, Sedić B (March 2010). "Side effects of treatment with benzodiazepines". Psychiatr Danub. 22 (1): 90–3. PMID 20305598.
  26. ↑ "apps.who.int" (PDF).
  27. ↑ Camfield CS, Chaplin S, Doyle AB, Shapiro SH, Cummings C, Camfield PR (September 1979). "Side effects of phenobarbital in toddlers; behavioral and cognitive aspects". J. Pediatr. 95 (3): 361–5. PMID 381616.
  28. ↑ French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE, Sachdeo RC, Beydoun A, Glauser TA (April 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 (8): 1252–60. PMID 15111659.
  29. ↑ Pulman J, Marson AG, Hutton JL, French JA, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, Theodore WH, Bazil C, Stern J, Schachter SC, Bergen D, Hirtz D, Montouris GD, Nespeca M, Gidal B, Marks WJ, Turk WR, Fischer JH, Bourgeois B, Wilner A, Faught RE, Sachdeo RC, Beydoun A, Glauser TA (May 2012). "Tiagabine add-on for drug-resistant partial epilepsy". Cochrane Database Syst Rev. 62 (5): CD001908. doi:10.1002/14651858.CD001908.pub2. PMC 4058679. PMID 22592677.
  30. ↑ Hemming K, Maguire MJ, Hutton JL, Marson AG (January 2013). "Vigabatrin for refractory partial epilepsy". Cochrane Database Syst Rev (1): CD007302. doi:10.1002/14651858.CD007302.pub2. PMID 23440814.
  31. ↑ "Vigabatrin (Sabril) for epilepsy". Med Lett Drugs Ther. 52 (1332): 14–6, quiz 17. February 2010. PMID 20208475.
  32. ↑ Chadwick D (July 1999). "Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group". Lancet. 354 (9172): 13–9. PMID 10406359.
  33. ↑ "Drugs@FDA: FDA Approved Drug Products".
  34. ↑ Coyle H, Clough P, Cooper P, Mohanraj R (December 2014). "Clinical experience with perampanel: focus on psychiatric adverse effects". Epilepsy Behav. 41: 193–6. doi:10.1016/j.yebeh.2014.09.072. PMID 25461214.
  35. ↑ French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, Kumar D, Rogawski MA (August 2012). "Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304". Neurology. 79 (6): 589–96. doi:10.1212/WNL.0b013e3182635735. PMC 3413761. PMID 22843280.
  36. ↑ Bourgeois BF (1994). "Felbamate in the treatment of partial-onset seizures". Epilepsia. 35 Suppl 5: S58–61. PMID 8039474.
  37. ↑ O'Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S (May 1996). "Felbamate-associated fatal acute hepatic necrosis". Neurology. 46 (5): 1457–9. PMID 8628501.
  38. ↑ Pulman J, Jette N, Dykeman J, Hemming K, Hutton JL, Marson AG (February 2014). "Topiramate add-on for drug-resistant partial epilepsy". Cochrane Database Syst Rev (2): CD001417. doi:10.1002/14651858.CD001417.pub3. PMID 24570033.
  39. ↑ Ramsay E, Faught E, Krumholz A, Naritoku D, Privitera M, Schwarzman L, Mao L, Wiegand F, Hulihan J (October 2010). "Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial". Epilepsia. 51 (10): 1970–7. doi:10.1111/j.1528-1167.2010.02670.x. PMID 20633037.
  40. ↑ Majkowski J, Neto W, Wapenaar R, Van Oene J (May 2005). "Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine". Epilepsia. 46 (5): 648–53. doi:10.1111/j.1528-1167.2005.35904.x. PMID 15857429.
  41. ↑ Loiseau P (1984). "Rational use of valproate: indications and drug regimen in epilepsy". Epilepsia. 25 Suppl 1: S65–72. PMID 6425050.
  42. ↑ Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS (January 2001). "Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy". Neurology. 56 (2): 172–7. PMID 11160951.
  43. ↑ Endo A, Fujita Y, Fuchigami T, Takahashi S, Mugishima H (April 2010). "Fanconi syndrome caused by valproic acid". Pediatr. Neurol. 42 (4): 287–90. doi:10.1016/j.pediatrneurol.2009.12.003. PMID 20304335.
  44. ↑ Gerstner T, Teich M, Bell N, Longin E, Dempfle CE, Brand J, König S (July 2006). "Valproate-associated coagulopathies are frequent and variable in children". Epilepsia. 47 (7): 1136–43. doi:10.1111/j.1528-1167.2006.00587.x. PMID 16886976.
  45. ↑ Sahota P, Prabhakar S, Kharbanda PS, Bhansali A, Jain V, Das CP, Modi M (December 2008). "Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study". Epilepsia. 49 (12): 2069–77. doi:10.1111/j.1528-1167.2008.01676.x. PMID 18503558.
  46. ↑ Aggarwal A, Rastogi N, Mittal H, Chillar N, Patil R (September 2011). "Thyroid hormone levels in children receiving carbamazepine or valproate". Pediatr. Neurol. 45 (3): 159–62. doi:10.1016/j.pediatrneurol.2011.04.005. PMID 21824562.
  47. ↑ Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, Kwan P (December 2015). "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. 56 (12): 1890–8. doi:10.1111/epi.13212. PMID 26471380.
  48. ↑ Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, Kwan P (December 2015). "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. 56 (12): 1890–8. doi:10.1111/epi.13212. PMID 26471380.
  49. ↑ "Drugs@FDA: FDA Approved Drug Products".
  50. ↑ Klein P, Schiemann J, Sperling MR, Whitesides J, Liang W, Stalvey T, Brandt C, Kwan P (December 2015). "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. 56 (12): 1890–8. doi:10.1111/epi.13212. PMID 26471380.

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