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anticonvulsant

See specific agent Indications: - prevention & treatment of seizures - epilepsy - myoclonic epilepsy - post-stroke epilepsy - Lennox-Gastaut syndrome - *also used for treatment of: [7] - *akathisia, attention-deficit hyperactivity disorder, pain, trigeminal neuralgia, glossopharyngeal neuralgia, neuropathic pain, postoperative pain, post herpetic neuralgia, migraine prophylaxis, anxiety, panic disorder, alcoholic withrawal syndrome, delirium tremens, ischemic heart disease, menopause, hot flash, essential tremor, head injury, amnesia, depression, bipolar disorder, mania, tetanus, muscle spasms, infantile spasms. restless legs syndrome - used in narcoanalysis, general anesthesia, neurosurgery, sedation [7] Dosage: - generics may differ in bioavailability by as much as 20% - use same manufacturer from month to month [10] - consider tapering of dosage if - seizure-free for 2-5 years - not juvenile myoclonic epilepsy - history of difficulty in seizure control - risk factors for epilepsy Adverse effects: 1) suicide, 2-fold risk of suicidal behavior or ideation compared to patients receiving placebo 2) withdrawal effects with abrupt discontinuation [3] a) seizures may occur b) taper 20-25% of dose/week 3) Stevens-Johnson syndrome -> toxic epidermal necrolysis 4) major congenital malformations range from 2.0-4.2% vs 2.2% in unexposed group [4] - valproate with highest risk (RR= 9.0, 25% >1450 mg/day) - lamotrigine with lowest risk (2.5% < 326 mg/day) [13] 5) probably not associated with increased risk for miscarriage or stillbirth [9] 6) may increase bone catabolism (supplement vitamin D & calcium) [10] - osteopenia & osteoporosis less with lamotrigine or levetiracetam than carbamazepine, phenytoin, valproate, phenobarbital [10] 7) association between epilepsy & cardiovascular events in elderly largely due to enzyme-inducing anticonvulsants [16] - strong enzyme-inducing anticonvulsants include: - carbamazepine, phenytoin, phenobarbital, & primidone - weak enzyme-inducing anticonvulsants include: - oxcarbazepine, eslicarbazepine, topiramate, & rufinamide - of the cardiovascular events, strong enzyme-inducing anticonvulsant appear to have the largest effect on myocardial infarction (59%) [16] Drug interactions: - some antibiotics, antihistamines, antipsychotics & analgesics can lower the seizure threshold & interact negatively with anticonvulsants (see drugs causing seizures) [10] - anticonvulsants may increase statin clearance [10] Notes: - change in pill color may be associated with non-compliance, especially in patients with anticonvulsants [5] - lamotrigine, levetiracetam, topiramate, valproate & zonisamide are broad spectrum agents that may be used to treat both generalized & partial seizures [10] - among anticonvulsants used as monotherapy in poststroke epilepsy, lamotrigine is associated with the lowest risk for mortality, valproate the highest [15]

Interactions

drug interactions drug adverse effects of anticonvulsants monitor with anticonvulsants

Specific

amobarbital (Amytal) brivaracetam (Briviact) carbamazepine; CBZ (Tegretol, Atretol, Eiptol, Carbatrol, Equetro) cenobamate (Xcopri) clonazepam (Klonopin) diazepam (Vallium, Diastat) eslicarbazepine acetate (Aptiom) ethosuximide (Zarontin) ethotoin; 3-ethyl-5-phenyl-2,4-imidazolidinedione (Peganone) ezogabine (Potiga, retigabine) felbamate (Felbatol) fosphenytoin (Cerebyx) gabapentinoid; GABA analog ganaxolone (Ztalmy) lacosamide (Vimpat, erlosamide, harkoseride) lamotrigine (Lamictal, Lamictal ODT, Lamictal XR) levetiracetam (Keppra, Etiracetam, Spritam) mephenytoin; methoin; methylphenylethylhydantoin (Mesantoin) methsuximide (Celontin, Kapseal) oxcarbazepine (Trileptal) paramethadione; paradione perampanel (Fycompa) phenacemide; phenylacetylurea; phenurone; cetylureum phenobarbital; PB; PHB (Luminal, Barbita, Solfoton) phensuximide (Milontin) phenylethylmalonamide (PEMA) phenytoin; diphenylhydantoin; PTN (Dilantin, Dephenylan, Antilepsin) primidone; desoxyphenobarbital (Primaclone, Mysoline) rufinamide (Banzel, Inovelon, Xilep) stiripentol (Diacomit) sulthiame; trolone; sulphenyltame; sulthiamine; (Ospolot) tiagabine (Gabitril) topiramate (Topamax, Qudexy XR, Trokendi XR) trimethadione (Tridione) valproic acid; n-dipropylacetic acid (Depakene, Depakote, Divalproex, Mylproin, Valontin, Stavzor) vigabatrin (Sabril) zonisamide (Zonegran)

General

neurologic agent

References

  1. Prescriber's Letter 11(12): 2004 Comparison of FDA-Approved Antiepileptic Drugs Detail-Document#: 201213 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 14(7): 2007 Generic Substitution of Antiepileptic Drugs Detail-Document#: 230712 (subscription needed) http://www.prescribersletter.com
  3. FDA News FDA Requires Warnings about Risk of Suicidal Thoughts and Behavior for Antiepileptic Medications Dec. 16, 2008 http://www.fda.gov/bbs/topics/NEWS/2008/NEW01927.html
  4. Hernandez-Diaz S et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012 May 22; 78:1692. PMID: 22551726
  5. Kesselheim AS et al. Variations in pill appearance of antiepileptic drugs and the risk of nonadherence. Arch Intern Med 2012 Dec 31 PMID: 23277164 http://archinte.jamanetwork.com/article.aspx?articleid=1487287
  6. Arif H, Buchsbaum R, Pierro J et al Comparative effectiveness of 10 antiepileptic drugs in older adults with epilepsy. Arch Neurol. 2010 Apr;67(4):408-15 PMID: 20385905
  7. Deprecated Reference
  8. Arif H, Buchsbaum R, Weintraub D et al Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology. 2007 May 15;68(20):1701-9. PMID: 17502552
  9. Bech BH et al Use of antiepileptic drugs during pregnancy and risk of spontaneous abortion and stillbirth: population based cohort study. BMJ 2014;349:g5159 PMID: 25150301 http://www.bmj.com/content/349/bmj.g5159
  10. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  11. Glauser T, Ben-Menachem E, Bourgeois B et al Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013 Mar;54(3):551-63. PMID: 23350722
  12. Israni RK, Kasbekar N, Haynes K, Berns JS. Use of antiepileptic drugs in patients with kidney disease. Semin Dial. 2006 Sep-Oct;19(5):408-16. PMID: 16970741
  13. Tomson T, Battino D, Bonizzoni E, et al Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurology. April 18, 2018 PMID: 29680205 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30107-8/fulltext - Pennell PB Prescribing antiepileptic drugs to women of reproductive age. Lancet Neurology. April 18, 2018 PMID: 29680207 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30154-6/fulltext
  14. Schmidt D. Starting, Choosing, Changing, and Discontinuing Drug Treatment for Epilepsy Patients. Neurol Clin. 2016 May;34(2):363-81, viii. Review. PMID: 27086984
  15. Swift Yasgur B Lamotrigine Linked to Lowest Mortality Risk in Poststroke Epilepsy. Medscape. Jan 7, 2022 https://www.medscape.com/viewarticle/966285
  16. Li J, Shlobin NA, Thijs RD et al Antiseizure Medications and Cardiovascular Events in Older People With Epilepsy. JAMA Neurol. 2024 Sep 30. PMID: 39348143 https://jamanetwork.com/journals/jamaneurology/fullarticle/2824203