Wikipedia

Anticonvulsant

(Redirected fromAntiepileptic)

Anticonvulsants(also known asantiepileptic drugs,antiseizure drugs,oranti-seizure medications(ASM)) are a diverse group ofpharmacologicalagents used in the treatment ofepilepticseizures.[1]Anticonvulsants are also increasingly being used in the treatment ofbipolar disorder[2][3]andborderline personality disorder,[4]since many seem to act asmood stabilizers,and for the treatment ofneuropathic pain.[5]Anticonvulsants suppress the excessive rapid firing ofneuronsduring seizures.[6]Anticonvulsants also prevent the spread of the seizure within the brain.[7]

Anticonvulsant
Drug class
Class identifiers
SynonymsAntiepileptic drugs, antiseizure drugs
UseEpilepsy
ATC codeN03
Biological targetBrain
Legal status
In Wikidata

Conventional antiepileptic drugs may blocksodium channelsor enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action.[8]Next to thevoltage-gated sodium channelsand components of the GABA system, their targets includeGABAAreceptors,theGABA transporter type 1,andGABA transaminase.[9]Additional targets include voltage-gatedcalcium channels,SV2A,andα2δ.[10][11]By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatoryglutamate,whose release is considered to be elevated in epilepsy, but also that of GABA.[12]This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act proconvulsively.[12]Another potential target of antiepileptic drugs is theperoxisome proliferator-activated receptor Alpha.[13][14][15][16][17][18][19]

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy.[20]That is, they either prevent the development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown in human trials to preventepileptogenesis(the development of epilepsy in an individual at risk, such as after ahead injury).[21]

Many anticonvulsants are knownteratogensand increase the risk of birth defects in the unborn child if taken while pregnant.[22]

Terminology

edit

Anticonvulsants are more accurately called antiepileptic drugs (AEDs) because not every epileptic seizure involvesconvulsion,and vice versa, not every convulsion is caused by an epileptic seizure.[23]They are also often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.[24]

Approval

edit

The usual method of achieving approval for a drug is to show it is effective when compared againstplacebo,or that it is more effective than an existing drug. In monotherapy (where only one drug is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is uncontrolled by their medication (i.e., it is refractory to treatment) are selected to see if supplementing the medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo.[21]The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earnedFDAapproval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments and has approved many more. Despite their lack of FDA approval, theAmerican Academy of Neurologyand theAmerican Epilepsy Societystill recommend a number of these new drugs as initial monotherapy.[21]

Drugs

edit

In the following list, the dates in parentheses are the earliest approved use of the drug.

Aldehydes

edit
Main article:Aldehyde

Aromatic allylic alcohols

edit

Barbiturates

edit
Main article:Barbiturate

Barbituratesaredrugsthat act ascentral nervous system(CNS)depressants,and by virtue of this they produce a wide spectrum of effects, from mildsedationtoanesthesia.The following areclassifiedas anticonvulsants:[31]

Benzodiazepines

edit
Main article:Benzodiazepine

The benzodiazepines are a class ofdrugswithhypnotic,anxiolytic,anticonvulsive,amnesticandmuscle relaxantproperties. Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development oftoleranceto the anticonvulsant effects anddependency.[32][33][34][35]Of many drugs in this class, only a few are used to treat epilepsy:

The following benzodiazepines are used to treatstatus epilepticus:

  • Diazepam(1963). Can be given rectally by trained care-givers.
  • Midazolam(N/A). Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by thebuccal mucosa.
  • Lorazepam(1972). Given by injection in hospital.

Nitrazepam,temazepam,and especiallynimetazepamare powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strongsedativeand motor-impairing properties.

Bromides

edit
Main article:Bromide
  • Potassium bromide(1857). The earliest effective treatment for epilepsy. There would not be a better drug until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats but is no longer used in humans.

Carbamates

edit
Main article:Carbamate
  • Felbamate(1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.[36][37][38]
  • Cenobamate(2019).

Carboxamides

edit
Carbamazepine
Main article:Carboxamide

The following are carboxamides:

  • Carbamazepine(1963). A popular anticonvulsant that is available in generic formulations.
  • Oxcarbazepine(1990). A derivative of carbamazepine that has similar efficacy and is better tolerated and is also available generically.
  • Eslicarbazepine acetate(2009).
  • Photoswitchable analogues of carbamazepine (2024) are research compounds developed to control its pharmacological activity locally and on demand using light, with the purpose to reduce adverse systemic effects.[39]One of these compounds (carbadiazocine, based on a bridgedazobenzene) has been shown to produce analgesia with noninvasive illumination in a rat model ofneuropathic pain.

Fatty acids

edit
Main article:Fatty acid

The following are fatty-acids:

Vigabatrin and progabide are also analogs of GABA.

Fructose derivatives

edit
Main article:Fructose

Gabapentinoids

edit
Main article:Gabapentinoid
GABAanalogues
Voltage-gated calcium channel

Gabapentinoids are used inepilepsy,neuropathic pain,fibromyalgia,restless leg syndrome,opioid withdrawalandgeneralized anxiety disorder(GAD). Gabapentinoids blockvoltage-gated calcium channels,mainly theN-Type,andP/Q-type calcium channels. The following are gabapentinoids:

Gabapentinoids are analogs of GABA, but they do not act on GABA receptors. They have analgesic, anticonvulsant, and anxiolytic effects.

Hydantoins

edit
Main article:Hydantoin

The following are hydantoins:

Oxazolidinediones

edit
Main article:2,4-Oxazolidinedione

The following are oxazolidinediones:

Propionates

edit
Main article:Propionate

Pyrimidinediones

edit
Main article:Pyrimidinedione

Pyrrolidines

edit
Main article:Pyrrolidine

Succinimides

edit
Main article:Succinimide

The following are succinimides:

Sulfonamides

edit
Main article:Sulfonamide (medicine)

Triazines

edit
Main article:Triazine

Ureas

edit
Main article:Urea

Valproylamides

edit
Main article:Amide

Other

edit

Non-pharmaceutical anticonvulsants

edit
Further information:Epilepsy § Management

Theketogenic dietandvagus nerve stimulationare alternative treatments for epilepsy without the involvement of pharmaceuticals. The ketogenic diet consists of a high-fat, low-carbohydrate diet, and has shown good results in patients whose epilepsy has not responded to medications and who cannot receive surgery. The vagus nerve stimulator is a device that can be implanted into patients with epilepsy, especially that whichoriginates from a specific part of the brain.However, both of these treatment options can cause severe adverse effects. Additionally, while seizure frequency typically decreases, they often do not stop entirely.[40][41]

Treatment guidelines

edit

According to guidelines by theAmerican Academy of NeurologyandAmerican Epilepsy Society,[42]mainly based on a majorarticle reviewin 2004,[43]patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such ascarbamazepine,phenytoin,valproic acid/valproate semisodium,phenobarbital,or on the newer anticonvulsantsgabapentin,lamotrigine,oxcarbazepineortopiramate.The choice of anticonvulsants depends on individual patient characteristics.[42]Both newer and older drugs are generally equally effective in new onset epilepsy.[42]The newer drugs tend to have fewer side effects.[42]For newly diagnosedpartialormixed seizures,there is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate asmonotherapy.[42]Lamotriginecan be included in the options for children with newly diagnosedabsence seizures.[42]

History

edit

The first anticonvulsant wasbromide,suggested in 1857 by the British gynecologistCharles Locockwho used it to treat women with "hysterical epilepsy" (probablycatamenial epilepsy). Bromides are effective against epilepsy, and also causeimpotence,which is not related to its anti-epileptic effects. Bromide also suffered from the way it affected behaviour, introducing the idea of the "epileptic personality" which was actually a result of medication.Phenobarbitalwas first used in 1912 for both its sedative and antiepileptic properties. By the 1930s, the development of animal models in epilepsy research led to the development ofphenytoinbyTracy PutnamandH. Houston Merritt,which had the distinct advantage of treating epileptic seizures with less sedation.[44]By the 1970s, aNational Institutes of Healthinitiative, the Anticonvulsant Screening Program, headed by J. Kiffin Penry, served as a mechanism for drawing the interest and abilities of pharmaceutical companies in the development of new anticonvulsant medications.

Marketing approval history

edit

The following table lists anticonvulsant drugs together with the date their marketing was approved in the US, UK and France. Data for the UK and France are incomplete. TheEuropean Medicines Agencyapproves drugs throughout the European Union. Some of the drugs are no longer marketed.

Drug Brand US UK France
acetazolamide Diamox 1953-07-2727 July 1953[45] 1988[46]
brivaracetam Briviact 2016-02-1818 February 2016[47][48]
carbamazepine Tegretol 1974-07-1515 July 1974[49][50] 1965[46] 1963[51]
cenobamate Xcopri 2019-11-2121 November 2019
clobazam Onfi/Frisium 2011-10-2121 October 2011[52][53] 1979[46]
clonazepam Klonopin/Rivotril 1975-06-044 June 1975[54] 1974[46]
diazepam Valium 1963-11-1515 November 1963[55]
divalproex sodium Depakote 1983-03-1010 March 1983[56]
eslicarbazepine Aptiom 2013-08-1111 August 2013[57][58]
ethosuximide Zarontin 1960-11-022 November 1960[59] 1955[46] 1962[51]
ethotoin Peganone 1957-04-2222 April 1957[60]
everolimus Afinitor/Votubia 2009-03-3030 January 2009[61]
felbamate Felbatol 1993-07-2929 July 1993[62]
fosphenytoin Cerebyx 1996-08-055 August 1996[63]
gabapentin Neurontin 1993-12-3030 December 1993[64] 1993-05May 1993[46][51] 1994-10October 1994[51]
lacosamide Vimpat 2008-10-2828 October 2008[65]
lamotrigine Lamictal 1994-12-2727 December 1994[66] 1991-10October 1991[46][51] 1995-05May 1995[51]
levetiracetam Keppra 1999-11-3030 November 1999[67] 2000-09-2929 September 2000[46][68] 2000-09-2929 September 2000[68]
mephenytoin Mesantoin 1946-10-2323 October 1946[69]
metharbital Gemonil 1952[70][71]
methsuximide Celontin 1957-02-088 February 1957[72]
methazolamide Neptazane 1959-01-2626 January 1959[73]
oxcarbazepine Trileptal 2000-01-1414 January 2000[74] 2000[46]
phenobarbital Luminal Unknown 1912[46] 1920[51]
phenytoin Dilantin/Epanutin 1938[51][75] 1938[46] 1941[51]
piracetam Nootropil never approved
phensuximide Milontin 1953[76][77]
pregabalin Lyrica 2004-12-3030 December 2004[78] 2004-07-066 July 2004[46][79] 2004-07-066 July 2004[79]
primidone Mysoline 1954-03-088 March 1954[80] 1952[46] 1953[51]
rufinamide Banzel/Inovelon 2008-11-1414 November 2008[81][82]
sodium valproate Epilim Unknown 1977-12December 1977[51] 1967-06June 1967[51]
stiripentol Diacomit 2018-08-2020 August 2018[83][84] 2007-01January 2007[29] 2007-01January 2007[29]
tiagabine Gabitril 1997-09-3030 September 1997[85][86] 1998[46] 1997-11November 1997[51]
topiramate Topamax 1996-12-2424 December 1996[87] 1995[46]
trimethadione Tridione 1946-01-2525 January 1946[88]
valproic acid Depakene/Convulex 1978-02-2828 February 1978[89] 1993[46]
vigabatrin Sabril 2009-08-2121 August 2009[90] 1989[46]
zonisamide Zonegran 2000-03-2727 March 2000[91] 2005-03-1010 March 2005[46][92] 2005-03-1010 March 2005[92]

Pregnancy

edit
See also:Epilepsy and pregnancy

Many of the commonly usedanticonvulsant/anti-seizuremedications (ASMs), such as valproate, phenytoin, carbamazepine, phenobarbitol, gabapentin have been reported to cause an increased risk ofbirth defectsincluding major congenital malformations such as neural tube defects.[93]The risk of birth defects associated with taking these medications while pregnant may be dependent on the dose and on the timing of gestation (how well developed the baby is).[93]While trying to conceive a child and during pregnancy, medical advice should be followed to optimize the management of the person's epilepsy in order to keep the person and the unborn baby safe from epileptic seizures and also ensure that the risk of birth defects due toin uteroexposure of anticonvulsants is as low as possible. Use of anticonvulsant medications should be carefully monitored during use in pregnancy.[94]For example, since the first trimester is the most susceptible period for fetal development, planning a routine antiepileptic drug dose that is safer for the first trimester could be beneficial to prevent pregnancy complications.[95]

Valproic acid,and its derivatives such assodium valproateanddivalproex sodium,causescognitive deficitin the child, with an increased dose causing decreasedintelligence quotientand use is associated with adverse neurodevelopmental outcomes (cognitive and behavioral) in children.[96][97]On the other hand, evidence is conflicting forcarbamazepineregarding any increased risk ofcongenital physical anomaliesorneurodevelopmental disordersby intrauterine exposure.[96]Similarly, children exposedlamotrigineorphenytoinin the womb do not seem to differ in their skills compared to those who were exposed to carbamazepine.[96]

There is inadequate evidence to determine if newborns of women with epilepsy taking anticonvulsants have a substantially increased risk ofhemorrhagic disease of the newborn.[94]

There is little evidence to suggest that anticonvulsant/ASM exposure through breastmilk has clinical effects on newborns. TheMaternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)study showed that most blood concentrations in breastfed infants of mothers taking carbamazepine, oxcarbazepine, valproate, levetiracetam, and topiramate were quite low, especially in relationship to the mother's level and what the fetal level would have been during pregnancy. (Note: valproic acid is NOT a recommended ASM for people with epilepsy who are considering having children.)[98]

Infant exposure to newer ASMs (cenobamate, perampanel, brivaracetam, eslicarbazepine, rufinamide, levetiracetam, topiramate, gabapentin, oxcarbazepine, lamotrigine, and vigabatrin) via breastmilk was not associated with negative neurodevelopment (such as lower IQ and autism spectrum disorder) at 36 months.[99]

Several studies that followed children exposed to ASMs during pregnancy showed that a number of widely used ones (including lamotrigine and levetiracetam) carried a low risk of adverse neurodevelopmental outcomes (cognitive and behavioral) in children when compared to children born to mothers without epilepsy and children born to mothers taking other anti-seizure medications. Data from several pregnancy registries showed that children exposed to levetiracetam or lamotrigine during pregnancy had the lowest risk of developing major congenital malformations compared to those exposed to other ASMs. The risk of major congenital malformations for children exposed to these ASMs were within the range for children who were not exposed to any ASMs during pregnancy.[100]

People with epilepsycanhave healthy pregnancies and healthy babies. However, proper planning and care is essential to minimize the risk of congenital malformations or adverse neurocognitive outcomes for the fetus while maintaining seizure control for the pregnant person with epilepsy. If possible, when planning pregnancy, people with epilepsy should switch to ASMs with the lowest teratogenic risk for major congenital malformations as well as the least risk of adverse neurodevelopmental outcomes (e.g., lower IQ or autism spectrum disorder). They should also work with their healthcare providers to identify the lowest effective ASM dosage that will maintain their seizure control while regularly checking medication levels throughout pregnancy.[101]

Data from studies conducted on women taking antiepileptic drugs for non-epileptic reasons, including depression and bipolar disorder, show that if high doses of the drugs are taken during the first trimester of pregnancy then there is the potential of an increased risk of congenital malformations.[102]

Research

edit

The mechanism of how anticonvulsants cause birth defects is not entirely clear. Duringpregnancy,the metabolism of many anticonvulsants is affected. There may be an increase in the clearance and resultant decrease in the blood concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative.[94]In animal models, several anticonvulsant drugs have been demonstrated to induce neuronalapoptosisin the developing brain.[103][104][105][106][107]

References

edit
  1. ^Al-Otaibi F (1 September 2019)."An overview of structurally diversified anticonvulsant agents".Acta Pharmaceutica (Zagreb, Croatia).69(3). Walter de Gruyter GmbH:321–344.doi:10.2478/acph-2019-0023.ISSN1846-9558.PMID31259739.
  2. ^Joshi A, Bow A, Agius M (2019). "Pharmacological Therapies in Bipolar Disorder: a Review of Current Treatment Options".Psychiatria Danubina.31(Suppl 3):595–603.ISSN0353-5053.PMID31488797.
  3. ^Keck PE Jr,McElroy SL,Strakowski SM (1998). "Anticonvulsants and antipsychotics in the treatment of bipolar disorder".The Journal of Clinical Psychiatry.59(Suppl 6):74–82.PMID9674940.
  4. ^American Psychiatric Association, and American Psychiatric Association. Work Group on Borderline Personality Disorder. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Pub, 2001.
  5. ^Rogawski MA, Löscher W (2004)."The neurobiology of antiepileptic drugs".Nature Reviews Neuroscience.5(7):553–564.doi:10.1038/nrn1430.PMID15208697.S2CID2201038.Archivedfrom the original on 16 December 2020.Retrieved20 September2020.
  6. ^McLean MJ, Macdonald RL (June 1986). "Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture".Journal of Pharmacology and Experimental Therapeutics.237(3):1001–1011.PMID3086538.
  7. ^Harden CL (1 May 1994). "New antiepileptic drugs".Neurology.44(5):787–95.doi:10.1212/WNL.44.5.787.PMID8190276.S2CID75925846.
  8. ^"Archived copy"(PDF).Archived fromthe original(PDF)on 3 November 2013.Retrieved28 January2013.{{cite web}}:CS1 maint: archived copy as title (link)
  9. ^Rogawski MA, Löscher W (July 2004)."The neurobiology of antiepileptic drugs".Nature Reviews Neuroscience.5(7):553–64.doi:10.1038/nrn1430.PMID15208697.S2CID2201038.Archivedfrom the original on 16 December 2020.Retrieved20 September2020.
  10. ^Rogawski MA, Bazil CW (July 2008)."New molecular targets for antiepileptic drugs: Alpha (2)delta, SV2A, and K(v)7/KCNQ/M potassium channels".Curr Neurol Neurosci Rep.8(4):345–52.doi:10.1007/s11910-008-0053-7.PMC2587091.PMID18590620.
  11. ^Meldrum BS, Rogawski MA (January 2007)."Molecular targets for antiepileptic drug development".Neurotherapeutics.4(1):18–61.doi:10.1016/j.nurt.2006.11.010.PMC1852436.PMID17199015.
  12. ^abKammerer M, Rassner, M. P., Freiman, T. M., Feuerstein, T. J. (2 May 2011). "Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes".Naunyn-Schmiedeberg's Archives of Pharmacology.384(1):47–57.doi:10.1007/s00210-011-0636-8.PMID21533993.S2CID1388805.
  13. ^Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, et al. (2013). Charpier S (ed.)."PPAR- Alpha agonists as novel antiepileptic drugs: preclinical findings".PLOS ONE.8(5): e64541.Bibcode:2013PLoSO...864541P.doi:10.1371/journal.pone.0064541.PMC3664607.PMID23724059.
  14. ^Citraro R, et al. (2013). "Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy".Neuropharmacology.69:115–26.doi:10.1016/j.neuropharm.2012.11.017.PMID23206503.S2CID27701532.
  15. ^Porta, N., Vallée, L., Lecointe, C., Bouchaert, E., Staels, B., Bordet, R., Auvin, S. (2009)."Fenofibrate, a peroxisome proliferator-activated receptor- Alpha agonist, exerts anticonvulsive properties".Epilepsia.50(4):943–8.doi:10.1111/j.1528-1167.2008.01901.x.PMID19054409.S2CID6796135.
  16. ^Lampen A, Carlberg C, Nau H (2001). "Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives".Eur J Pharmacol.431(1):25–33.doi:10.1016/S0014-2999(01)01423-6.PMID11716839.
  17. ^Maguire JH, Murthy AR, Hall IH (1985). "Hypolipidemic activity of antiepileptic 5-phenylhydantoins in mice".Eur J Pharmacol.117(1):135–8.doi:10.1016/0014-2999(85)90483-2.PMID4085542.
  18. ^Hall IH, Patrick MA, Maguire JH (1990). "Hypolipidemic activity in rodents of phenobarbital and related derivatives".Archiv der Pharmazie.323(9):579–86.doi:10.1002/ardp.19903230905.PMID2288480.S2CID46002731.
  19. ^Frigerio F, Chaffard G, Berwaer M, Maechler P (2006). "The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the fatty acid oleate".Biochem Pharmacol.72(8):965–73.doi:10.1016/j.bcp.2006.07.013.PMID16934763.
  20. ^Kaminski RM, Rogawski MA, Klitgaard H (2014)."The potential of antiseizure drugs and agents that act on novel molecular targets as antiepileptogenic treatments".Neurotherapeutics.11(2):385–400.doi:10.1007/s13311-014-0266-1.PMC3996125.PMID24671870.
  21. ^abcAbou-Khalil BW (2007)."Comparative Monotherapy Trials and the Clinical Treatment of Epilepsy".Epilepsy Currents.7(5):127–9.doi:10.1111/j.1535-7511.2007.00198.x.PMC2043140.PMID17998971.
  22. ^Güveli BT, Rosti RÖ, Güzeltaş A, Tuna EB, Ataklı D, Sencer S, Yekeler E, Kayserili H, Dirican A, Bebek N, Baykan B, Gökyiğit A, Gürses C (28 February 2017)."Teratogenicity of Antiepileptic Drugs".Clinical Psychopharmacology and Neuroscience.15(1):19–27.doi:10.9758/cpn.2017.15.1.19.ISSN1738-1088.PMC5290711.PMID28138106.
  23. ^"Antiseizure medication".Cleveland Clinic.Archivedfrom the original on 16 March 2024.Retrieved16 March2024.
  24. ^Rogawski M (2021). "Chapter 24: Antiseizure Drugs". In Katzung B (ed.).Basic and Clinical Pharmacology, 15th Edition.McGraw-Hill Education. pp.422–455.
  25. ^Browne TR. Paraldehyde, chlormethiazole, and lidocaine for treatment of status epilepticus. In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Status Epilepticus. Mechanisms of Brain Damage and Treatment (Advances in Neurology, Vol 34). New York, Raven Press 1983: 509–517
  26. ^Ramsay RE (1989). "Pharmacokinetics and clinical use of parenteral phenytoin, phenobarbital, and paraldehyde".Epilepsia.30(Suppl 2):S1 –S3.doi:10.1111/j.1528-1157.1989.tb05818.x.PMID2767008.S2CID44798815.
  27. ^Plosker GL (November 2012). "Stiripentol: in severe myoclonic epilepsy of infancy (dravet syndrome)".CNS Drugs.26(11):993–1001.doi:10.1007/s40263-012-0004-3.PMID23018548.S2CID42911844.
  28. ^"Public summary of positive opinion for orpphan opinion for orphan designation of stiripentol for the treatment of severe myoclonic epilepsy in infancy"(PDF).European Medicines Agency. 30 July 2007. Archived fromthe original(PDF)on 17 December 2013.Retrieved19 May2013.Doc.Ref.: EMEA/COMP/269/04
  29. ^abcd"Diacomit EPAR".European Medicines Agency.Archivedfrom the original on 12 November 2020.Retrieved8 November2020.
  30. ^"Diacomit- stiripentol capsule Diacomit- stiripentol powder, for suspension".DailyMed.15 May 2020.Archivedfrom the original on 6 August 2020.Retrieved8 November2020.
  31. ^Suddock JT, Kent KJ, Cain MD. Barbiturate Toxicity. 2023 Apr 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID 29763050.( 26 / August / 2023 )
  32. ^Browne TR (May 1976). "Clonazepam. A review of a new anticonvulsant drug".Arch Neurol.33(5):326–32.doi:10.1001/archneur.1976.00500050012003.PMID817697.
  33. ^Isojärvi JI, Tokola RA (December 1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability".J Intellect Disabil Res.42(1):80–92.PMID10030438.
  34. ^Tomson T, Svanborg E, Wedlund JE (May–June 1986). "Nonconvulsive status epilepticus".Epilepsia.27(3):276–85.doi:10.1111/j.1528-1157.1986.tb03540.x.PMID3698940.S2CID26694857.
  35. ^Djurić M, Marjanović B, Zamurović D (May–June 2001). "[West syndrome--new therapeutic approach]".Srp Arh Celok Lek.129(1):72–7.PMID15637997.
  36. ^Bourgeois BF, Dodson E, Nordli DR Jr, Pellock JM, Sankar R, eds. (16 December 2007).Pediatric epilepsy: diagnosis and therapy(3rd ed.). New York: Demos Medical Publishing.ISBN978-1-933864-16-7.
  37. ^French J, Smith, M, Faught, E, Brown, L (12 May 1999)."Practice advisory: The use of felbamate in the treatment of patients with intractable epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society".Neurology.52(8):1540–5.doi:10.1212/WNL.52.8.1540.PMID10331676.
  38. ^"Felbamate".MedlinePlus: U.S. National Library of Medicine.Archivedfrom the original on 20 May 2013.Retrieved19 May2013.
  39. ^Camerin L, Maleeva G, Gomila-Juaneda A, Suárez-Pereira I, Matera C, Prischich D, Opar E, Riefolo F, Berrocoso E, Gorostiza P (18 June 2024)."Photoswitchable carbamazepine analogs for non-invasive neuroinhibition in vivo".Angewandte Chemie International Edition.doi:10.1002/anie.202403636.hdl:2445/215169.ISSN1433-7851.
  40. ^D'Andrea Meira I (2019)."Ketogenic Diet and Epilepsy: What We Know So Far".Frontiers in Neuroscience.13:5.doi:10.3389/fnins.2019.00005.PMC6361831.PMID30760973.
  41. ^Pruthi S."Vagus nerve stimulation".Mayo Clinic.Archivedfrom the original on 20 July 2023.Retrieved20 July2023.
  42. ^abcdefAAN Guideline Summary for Clinicians – Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New Onset EpilepsyArchived24 February 2011 at theWayback MachineRetrieved on 29 June 2010
  43. ^French JA, Kanner AM, Bautista J, et al. (May 2004)."Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society"(PDF).Epilepsia.45(5):401–9.doi:10.1111/j.0013-9580.2004.06204.x.hdl:2027.42/65231.PMID15101821.S2CID12259676.Archivedfrom the original on 27 August 2021.Retrieved30 August2019.
  44. ^Eadie M, Bladin P (2001).A Disease Once Sacred: A History of the Medical Understanding of Epilepsy.John Libbey.ISBN978-0-86196-607-3.Retrieved29 June2024.
  45. ^"New Drug Application (NDA) 008943".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  46. ^abcdefghijklmnopqrEpilepsy Action: Druglist.Archived1 March 2011 at theWayback MachineRetrieved on 1 November 2007.
  47. ^"New Drug Application (NDA) 205836".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  48. ^"Drug Approval Package: Briviact (brivaracetam)".U.S.Food and Drug Administration(FDA).30 March 2016.Archivedfrom the original on 22 November 2019.Retrieved21 November2019.
  49. ^"New Drug Application (NDA) 016608".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.(Initial approval on 11 March 1968 was for trigeminal neuralgia.)
  50. ^Schain RJ (1 March 1978)."Pediatrics—Epitomes of Progress: Carbamazepine (Tegretol) in the Treatment of Epilepsy".Western Journal of Medicine.128(3):231–232.PMC1238063.PMID18748164.
  51. ^abcdefghijklmLoiseau PJ (June 1999)."Clinical Experience with New Antiepileptic Drugs: Antiepileptic Drugs in Europe".Epilepsia.40(Suppl 6): S3–8.doi:10.1111/j.1528-1157.1999.tb00925.x.PMID10530675.S2CID29638422.
  52. ^"New Drug Application (NDA) 202067".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 28 October 2020.Retrieved21 November2019.
  53. ^"Drug Approval Package: Onfi NDA #202067".U.S.Food and Drug Administration(FDA).20 August 2013.Archivedfrom the original on 22 November 2019.Retrieved21 November2019.
  54. ^"New Drug Application (NDA) 017533".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  55. ^"New Drug Application (NDA) 013263".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  56. ^"New Drug Application (NDA) 018723".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  57. ^"New Drug Application (NDA) 022416".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  58. ^"Drug Approval Package: Brand Name (Generic Name) NDA #".U.S.Food and Drug Administration(FDA).20 December 2013.Archivedfrom the original on 22 November 2019.Retrieved21 November2019.
  59. ^"New Drug Application (NDA) 012380".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 30 November 2017.Retrieved21 November2019.
  60. ^"New Drug Application (NDA) 010841".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  61. ^"New Drug Application (NDA) 022334".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 31 October 2020.Retrieved21 November2019.
  62. ^"New Drug Application (NDA) 020189".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 21 October 2020.Retrieved21 November2019.
  63. ^"New Drug Application (NDA) 020450".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  64. ^"New Drug Application (NDA) 020235".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  65. ^"New Drug Application (NDA) 022253".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  66. ^"New Drug Application (NDA) 020241".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 24 October 2020.Retrieved21 November2019.
  67. ^"New Drug Application (NDA) 021035".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 21 October 2020.Retrieved21 November2019.
  68. ^abEPAR: Keppra.Archived19 June 2009 at theWayback MachineRetrieved on 1 November 2007.
  69. ^"New Drug Application (NDA) 006008".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  70. ^"New Drug Application (NDA) 008322".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  71. ^Dodson, W. Edwin, Giuliano Avanzini, Shorvon, Simon D., Fish, David R., Emilio Perucca (2004).The treatment of epilepsy.Oxford: Blackwell Science. xxviii.ISBN978-0-632-06046-7.
  72. ^"New Drug Application (NDA) 010596".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  73. ^"New Drug Application (NDA) 011721".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  74. ^"New Drug Application (NDA) 021014".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  75. ^"New Drug Application (NDA) 008762".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 16 December 2020.Retrieved21 November2019.(Marketed in 1938, approved 1953)
  76. ^"New Drug Application (NDA) 008855".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 26 July 2020.Retrieved21 November2019.
  77. ^Kutt, Henn, Resor, Stanley R. (1992).The Medical treatment of epilepsy.New York: Dekker. p. 385.ISBN978-0-8247-8549-9.(first usage)
  78. ^"New Drug Application (NDA) 021446".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  79. ^abEPAR: LyricaArchived21 June 2009 at theWayback MachineRetrieved on 1 November 2007.
  80. ^"New Drug Application (NDA) 009170".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 24 October 2020.Retrieved21 November2019.
  81. ^"New Drug Application (NDA) 021911".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  82. ^"Drug Approval Package: Banzel (Rufinamide) NDA #021911".U.S.Food and Drug Administration(FDA).30 May 2012.Archivedfrom the original on 22 November 2019.Retrieved21 November2019.
  83. ^"New Drug Application (NDA) 206709".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 26 July 2020.Retrieved21 November2019.
  84. ^"Drug Approval Package: Diacomit (stiripentol)".U.S.Food and Drug Administration(FDA).7 September 2018.Archivedfrom the original on 22 November 2019.Retrieved21 November2019.
  85. ^"New Drug Application (NDA) 020646".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 16 December 2020.Retrieved21 November2019.
  86. ^"NDA: 020646".DrugPatentWatch.Archivedfrom the original on 23 March 2021.Retrieved19 May2013.
  87. ^"New Drug Application (NDA) 020505".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  88. ^"New Drug Application (NDA) 005856".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  89. ^"New Drug Application (NDA) 018081".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  90. ^"New Drug Application (NDA) 020427".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 20 October 2020.Retrieved21 November2019.
  91. ^"New Drug Application (NDA) 020789".Drugs@FDA.U.S.Food and Drug Administration(FDA).Archivedfrom the original on 19 October 2020.Retrieved21 November2019.
  92. ^abEPAR: Zonegran.Archived13 July 2009 at theWayback MachineRetrieved on 1 November 2007
  93. ^abBromley R, Adab N, Bluett-Duncan M, Clayton-Smith J, Christensen J, Edwards K, Greenhalgh J, Hill RA, Jackson CF, Khanom S, McGinty RN, Tudur Smith C, Pulman J, Marson AG (29 August 2023)."Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child".The Cochrane Database of Systematic Reviews.2023(8): CD010224.doi:10.1002/14651858.CD010224.pub3.ISSN1469-493X.PMC10463554.PMID37647086.
  94. ^abcHarden CL, Pennell PB, Koppel BS, et al. (May 2009)."Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society".Epilepsia.50(5):1247–55.doi:10.1111/j.1528-1167.2009.02130.x.PMID19507305.S2CID221731995.
  95. ^George IC (2017)."Practice Current: How do you treat epilepsy in pregnancy?".Neurology: Clinical Practice.7(4):363–371.doi:10.1212/cpj.0000000000000387.ISSN2163-0402.PMC5648199.PMID29185530.
  96. ^abcBromley R, Weston J, Adab N, Greenhalgh J, Sanniti A, McKay AJ, Tudur Smith C, Marson AG (2014)."Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child".Reviews.2020(10): CD010236.doi:10.1002/14651858.CD010236.pub2.PMC7390020.PMID25354543.
  97. ^Tomson T, Marson A, Boon P, Canevini MP, Covanis A, Gaily E, Kälviäinen R, Trinka E (July 2015)."Valproate in the treatment of epilepsy in girls and women of childbearing potential".Epilepsia.56(7):1006–1019.doi:10.1111/epi.13021.ISSN0013-9580.PMID25851171.Archivedfrom the original on 1 March 2024.Retrieved1 March2024.
  98. ^Birnbaum AK, Meador KJ, Karanam A, Brown C, May RC, Gerard EE, Gedzelman ER, Penovich PE, Kalay gian LA, Cavitt J, Pack AM, Miller JW, Stowe ZN, Pennell PB, for the MONEAD Investigator Group (1 April 2020)."Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy".JAMA Neurology.77(4):441–450.doi:10.1001/jamaneurol.2019.4443.ISSN2168-6149.PMC6990802.PMID31886825.
  99. ^"Norwegian Mother, Father and Child Cohort Study (MoBa)".Norwegian Institute of Public Health.Archivedfrom the original on 12 October 2023.Retrieved11 October2023.
  100. ^Tomson T, Battino D, Perucca E (April 2019)."Teratogenicity of antiepileptic drugs".Current Opinion in Neurology.32(2):246–252.doi:10.1097/WCO.0000000000000659.ISSN1473-6551.PMID30664067.S2CID58608931.Archivedfrom the original on 22 November 2023.Retrieved31 December2023.
  101. ^Pennell PB, Karanam A, Meador KJ, Gerard E, Kalay gian L, Penovich P, Matthews A, McElrath TM, Birnbaum AK, MONEAD Study Group (1 April 2022)."Antiseizure Medication Concentrations During Pregnancy: Results From the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Study".JAMA Neurology.79(4):370–379.doi:10.1001/jamaneurol.2021.5487.ISSN2168-6149.PMC8845026.PMID35157004.
  102. ^Jazayeri D, Graham J, Hitchcock A, O'Brien TJ, Vajda FJ (2018)."Outcomes of pregnancies in women taking antiepileptic drugs for non-epilepsy indications".Seizure.56:111–114.doi:10.1016/j.seizure.2018.02.009.ISSN1059-1311.PMID29471258.
  103. ^Bittigau P, Sifringer M, Genz K, et al. (May 2002)."Antiepileptic drugs and apoptotic neurodegenereation in the developing brain".Proceedings of the National Academy of Sciences of the United States of America.99(23):15089–94.Bibcode:2002PNAS...9915089B.doi:10.1073/pnas.222550499.PMC137548.PMID12417760.
  104. ^Manthey D, Asimiadou S, et al. (June 2005). "Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain".Exp Neurol.193(2):497–503.doi:10.1016/j.expneurol.2005.01.006.PMID15869952.S2CID1493015.
  105. ^Katz I, Kim J, et al. (August 2007). "Effects of lamotrigine alone and in combination with MK-801, phenobarbital, or phenytoin on cell death in the neonatal rat brain".J Pharmacol Exp Ther.322(2):494–500.doi:10.1124/jpet.107.123133.PMID17483293.S2CID12741109.
  106. ^Kim J, Kondratyev A, Gale K (October 2007)."Antiepileptic drug-induced neuronal cell death in the immature brain: effects of carbamazepine, topiramate, and levetiracetam as monotherapy versus polytherapy".J Pharmacol Exp Ther.323(1):165–73.doi:10.1124/jpet.107.126250.PMC2789311.PMID17636003.
  107. ^Forcelli PA, Kim J, et al. (December 2011)."Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain".Epilepsia.52(12): e207–11.doi:10.1111/j.1528-1167.2011.03297.x.PMC3230752.PMID22050285.

Further reading

edit
  • Anti epileptic activity of novel substituted fluorothiazole derivatives by Devid Chutia, RGUHS
edit
Retrieved from "https://en.wikipedia.org/w/index.php?title=Anticonvulsant&oldid=1271619355"