Abstract
Phenobarbital and primidone have long treatment traditions. Many of the clinical studies have been performed in limited groups of patients, and few randomized controlled trials comparing other relevant AEDs have been published. Side effects include CNS-related effects as sedation, and development of tolerance over time. Phenobarbital and primidone have linear pharmacokinetics, but have enzyme-inducing properties, affecting concomitant medication. Therapeutic drug monitoring is a tool to optimize the therapy with both phenobarbital and primidone in the individual patient. Phenobarbital has still a place in the treatment of various seizure forms, whereas the use of primidone, as a metabolite of phenobarbital, has a more limited place in modern treatment of epilepsy. Phenobarbital is one of the most available drugs in the world based upon the WHO list of essential medicines (WHO), due to its efficacy, low cost, and a possibility to balance efficacy and tolerability, especially in resource-limited areas.
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References
Bialer M. How did phenobarbital’s chemical structure affect the development of subsequent antiepileptic drugs (AEDs)? Epilepsia. 2012;53(Suppl 8):3–11.
Brodie MJ, Kwan P. Current position of phenobarbital in epilepsy and its future. Epilepsia. 2012;53(Suppl 8):40–6.
Feksi AT, Kaamugisha J, Sander JW, Gatiti S, Shorvon SD. Comprehensive primary health care antiepileptic drug treatment programme in rural and semi-urban Kenya. ICBERG (International Community-based Epilepsy Research Group). Lancet. 1991;337:406–9.
Heller AJ, Chesterman P, Elwes RD, Crawford P, Chadwick D, Johnson AL, Reynolds EH. Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial. J Neurol Neurosurg Psychiatry. 1995;58(1):44–50.
Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false alarm? Epilepsia. 2009;50(5):978–86.
Hole K, Wollmann BM, Nguyen C, Haslemo T, Molden E. Comparison of CYP3A4-inducing capacity of enzyme-inducing antiepileptic drugs using 4β-hydroxycholesterol as biomarker. Ther Drug Monit. 2018;40(4):463–8.
Johannessen SI, Landmark CJ. Antiepileptic drug interactions – principles and clinical implications. Curr Neuropharmacol. 2010;8(3):254–67.
Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia. 2004;45(9):1141–9.
Landmark CJ, Fossmark H, Larsson PG, Rytter E, Johannessen SI. Prescription patterns of antiepileptic drugs in patients with epilepsy in a nation-wide population. Epilepsy Res. 2011;95(1–2):51–9.
Landmark CJ, Johannessen SI, Tomson T. Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring. Epileptic Disord. 2016;18(4):367–83.
Löscher W, Rogawski MA. How theories evolved concerning the mechanism of action of barbiturates. Epilepsia. 2012;53(Suppl 8):12–25.
Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonicclonic seizures. N Engl J Med. 1985;313(3):145–151
Pal DK, Das T, Chaudhury G, Johnson AL, Neville BG. Randomised controlled trial to assess acceptability of phenobarbital for childhood epilepsy in rural India. Lancet. 1998;351:19–23.
Patsalos PN, Beryy DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs – best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49(7):1239–76.
Taylor S, Tudor Smith C, Williamson PR, Marson AG. Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic–clonic seizures. Cochrane Database Syst Rev. 2001;4:CD002217.
Tomson T, Battino D, Bonizzoni E, Craig J, Lindhout D, Sabers A, Perucca E, Vajda F, EURAP Study Group. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10(7):609–17.
Tsiropoulos I, Gichangi A, Andersen M, Bjerrum L, Gaist D, Hallas J. Trends in utilization of antiepileptic drugs in Denmark. Acta Neurol Scand. 2006;113(6):405–11. Erratum in: Acta Neurol Scand. 2006;114(1):70.
Tudor Smith C, Marson AG, Williamson PR. Carbamazepine versus phenobarbitone monotherapy for epilepsy. Cochrane Database Syst Rev. 2003;1:CD001904.
WHO. https://www.who.int/medicines/publications/essentialmedicines/en/ (2008). Accessed 18 Jan 2019.
Yasiry Z, Shorvon SD. How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years. Epilepsia. 2012;53(Suppl 8):26–39.
Zhang LL, Zeng LN, Li YP. Side effects of phenobarbital in epilepsy: a systematic review. Epileptic Disord. 2011;13(4):349–65.
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Johannessen, S.I., Johannessen Landmark, C. (2020). Anti-Convulsant Agents: Phenobarbital and Primidone. In: Riederer, P., Laux, G., Mulsant, B., Le, W., Nagatsu, T. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_302-1
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DOI: https://doi.org/10.1007/978-3-319-56015-1_302-1
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