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Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of
pharmacological Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
agents used in the treatment of
epileptic Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s. Anticonvulsants are also increasingly being used in the treatment of
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
and borderline personality disorder, since many seem to act as
mood stabilizers A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder. Uses Mood stabilizers are best known for th ...
, and for the treatment of
neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
. Anticonvulsants suppress the excessive rapid firing of
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid ( GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the
voltage-gated sodium channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chann ...
and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and
GABA transaminase In enzymology, 4-aminobutyrate transaminase (), also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction: :4-aminobutanoate + 2-oxoglutarate \rightleftharpoons succinate sem ...
. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatory glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA. 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. Another potential target of antiepileptic drugs is the
peroxisome proliferator-activated receptor alpha Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gene ...
. Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. 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 prevent
epileptogenesis Epileptogenesis is the gradual process by which a typical brain develops epilepsy. Epilepsy is a chronic condition in which seizures occur. These changes to the brain occasionally cause neurons to fire in an abnormal, hypersynchronous manner, know ...
(the development of epilepsy in an individual at risk, such as after a
head injury A head injury is any injury that results in trauma to the skull or brain. The terms ''traumatic brain injury'' and ''head injury'' are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of inju ...
).


Terminology

Anticonvulsants are more accurately called antiepileptic drugs (abbreviated "AEDs"), and are often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy.


Approval

The usual method of achieving approval for a drug is to show it is effective when compared against
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
, 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 currently 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. The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earned
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments and has approved many more. Despite their lack of FDA approval, the
American Academy of Neurology The American Academy of Neurology (AAN) is a professional society representing over 38,000 neurologists and neuroscientists. As a medical specialty society it was established in 1948 by A.B. Baker of the University of Minnesota to advance the ...
and the
American Epilepsy Society The American Epilepsy Society (AES) is a nationwide 501(c)(3) non-profit organization for medical professionals and scientific investigators dedicated to finding the prevention, treatment, and cure of epilepsy. History AES was founded in 1946 ...
still recommend a number of these new drugs as initial monotherapy.


Drugs

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


Aldehydes

*
Paraldehyde Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane, with a methyl group substituted for a hydrogen atom at each carbon. The corresponding tetramer is metaldehyde. A colourless liquid, it ...
(1882). One of the earliest anticonvulsants. It is still used to treat status epilepticus, particularly where there are no resuscitation facilities.


Aromatic allylic alcohols

*
Stiripentol Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder. The most common side effects include loss of appetite, weight loss, insomnia (difficu ...
(2007). Indicated for the treatment of
Dravet syndrome Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or feve ...
.


Barbiturates

Barbiturates are drugs that act as
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(CNS)
depressant A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
s, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. The following are classified as anticonvulsants: *
Phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...
(1912). See also the related drug
primidone Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures, as well as essential tremors. It is taken by mouth. Common side effects include sleepiness, poor coordination, nau ...
. *
Methylphenobarbital Methylphenobarbital (INN), also known as mephobarbital (USAN, JAN) and mephobarbitone ( BAN), marketed under brand names such as Mebaral, Mephyltaletten, Phemiton, and Prominal, is a drug which is a barbiturate derivative and is used primarily ...
(1935). Known as mephobarbital in the US. No longer marketed in the UK. * Barbexaclone (1982). Only available in some European countries. Phenobarbital was the main anticonvulsant from 1912 until the development of phenytoin in 1938. Today, phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as
lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and c ...
,
diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...
or
midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ...
is usually tried first. Other barbiturates only have an anticonvulsant effect at
anaesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
doses.


Benzodiazepines

The benzodiazepines are a class of drugs with
hypnotic Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
,
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...
, anticonvulsive,
amnestic Amnesia is a deficit in memory caused by brain damage or disease,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be caused temporarily by the use o ...
and
muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therap ...
properties. 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 of tolerance to the anticonvulsant effects and dependency. Of many drugs in this class, only a few are used to treat epilepsy: *
Clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselect ...
(1979). Notably, used on a short-term basis around menstruation in women with catamenial epilepsy. *
Clonazepam Clonazepam, sold under the brand names Klonopin and Rivotril, is a medication used to prevent and treat seizures, panic disorder, anxiety disorders, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine class ...
(1974). *
Clorazepate Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiaz ...
(1972). The following benzodiazepines are used to treat status epilepticus: *
Diazepam Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...
(1963). Can be given rectally by trained care-givers. *
Midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ...
(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 the
buccal mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed '' lamina propria''. The oral cavity has sometimes been des ...
. *
Lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and c ...
(1972). Given by injection in hospital.
Nitrazepam Nitrazepam, sold under the brand name Mogadon among others, is a hypnotic drug of the benzodiazepine class used for short-term relief from severe, disabling anxiety and insomnia. It also has sedative (calming) properties, as well as amnestic (i ...
,
temazepam Temazepam (sold under the brand names Restoril among others) is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hyp ...
, and especially
nimetazepam Nimetazepam (marketed under brand name Erimin and Lavol) is an intermediate-acting hypnotic drug which is a benzodiazepine derivative. It was first synthesized by a team at Hoffmann-La Roche in 1964. It possesses powerful hypnotic, anxiolytic, s ...
are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties.


Bromides

* 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

*
Felbamate Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures (with and without generalization) in adults and partial and generalized seizures associa ...
(1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.


Carboxamides

The following are carboxamides: *
Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
(1963). A popular anticonvulsant that is available in generic formulations. *
Oxcarbazepine Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with ...
(1990). A derivative of carbamazepine that has similar efficacy and is better tolerated and is also available generically. *
Eslicarbazepine acetate Eslicarbazepine acetate (ESL), sold under the brand names Aptiom and Zebinix among others, is an anticonvulsant medication approved for use in Europe and the United States as monotherapy or as additional therapy for partial-onset seizures epileps ...
(2009).


Fatty acids

The following are fatty-acids: * The valproates
valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
,
sodium valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
, and
divalproex sodium Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in thos ...
(1967). *
Vigabatrin Vigabatrin, brand name Sabril, is a medication used to treat epilepsy. It became available as a generic medication in 2019. It works by inhibiting the breakdown of γ-aminobutyric acid (GABA). It is also known as γ-vinyl-GABA, and is a stru ...
(1989). *
Progabide Progabide (INN; trade name Gabrene, Sanofi-Aventis) is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ re ...
(1987). *
Tiagabine Tiagabine (trade name Gabitril) is an anticonvulsant medication produced by Cephalon that is used in the treatment of epilepsy. The drug is also used off-label in the treatment of anxiety disorders and panic disorder. Medical uses Tiagabine is a ...
(1996). ''Vigabatrin and progabide are also analogs of GABA.''


Fructose derivatives

*
Topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...
(1995).


Gabapentinoids

Gabapentinoids are used in,
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...
,
neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
, fibromyalgia,
restless leg syndrome Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
,
opioid withdrawal Opioid withdrawal is a set of symptoms (a syndrome) arising from the sudden withdrawal or reduction of opioids where previous usage has been heavy and prolonged. Signs and symptoms of withdrawal can include drug craving, anxiety, restless legs, ...
and
generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...
(GAD). Gabapentinoids block
Voltage gated Calcium channels Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeabi ...
, mainly the N-Type, and P/Q type calcium channels. The following are Gabapentinoids: *
Pregabalin Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic and anxiolytic medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless leg syndrome, opioid withdrawal and generalized anxiety diso ...
(2004) * Mirogabalin (2019) (Japan only) *
Gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabeti ...
(1993) * Gabapentin Encarbil (2011). *
Gabapentin Extended Release Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabetic ...
(Gralise) (1996). ''Gabapentinoids are analogs of GABA, but they do not act on GABA. They have analgesic anticonvulsant and anxiolytic effects.''


Hydantoins

The following are hydantoins: * Ethotoin (1957). *
Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
(1938). *
Mephenytoin Mephenytoin (marketed as Mesantoin by Novartis) is a hydantoin, used as an anticonvulsant. It was introduced approximately 10 years after phenytoin, in the late 1940s. The significant metabolite of mephenytoin is nirvanol (5-ethyl-5-phenylhyda ...
. *
Fosphenytoin Fosphenytoin, also known as fosphenytoin sodium, and sold under the brand name Cerebyx among others, is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. ...
(1996).


Oxazolidinediones

The following are oxazolidinediones: * Paramethadione. *
Trimethadione Trimethadione (Tridione) is an oxazolidinedione anticonvulsant. It is most commonly used to treat epileptic conditions that are resistant to other treatments. It is primarily effective in treating absence seizures, but can also be used in ref ...
(1946). * Ethadione.


Propionates

* Beclamide.


Pyrimidinediones

*
Primidone Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures, as well as essential tremors. It is taken by mouth. Common side effects include sleepiness, poor coordination, nau ...
(1952).


Pyrrolidines

*
Brivaracetam Brivaracetam, sold under the brand names Briviact and Brivajoy among others, a chemical analog of levetiracetam, is a racetam derivative with anticonvulsant (antiepileptic) properties. It is marketed by the pharmaceutical company UCB. It is av ...
(2016). *
Etiracetam Etiracetam is a chemical compound belonging to the racetam family, which was developed as a nootropic drug. It is racemic; its biologically active enantiomeric form is levetiracetam Levetiracetam, sold under the brand name Keppra among others ...
. *
Levetiracetam Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formu ...
(1999). *
Seletracetam Seletracetam (UCB 44212) is a pyrrolidone-derived drug of the racetam family that is structurally related to levetiracetam (trade name Keppra). It was under development by UCB Pharmaceuticals as a more potent and effective anticonvulsant drug to ...
.


Succinimides

The following are succinimides: *
Ethosuximide Ethosuximide, sold under the brand name Zarontin among others, is a medication used to treat absence seizures. It may be used by itself or with other antiseizure medications such as valproic acid. Ethosuximide is taken by mouth. Ethosuximide i ...
(1955). *
Phensuximide Phensuximide is an anticonvulsant in the succinimide Succinimide is an organic compound with the formula (CH2)2(CO)2NH. This white solid is used in a variety of organic syntheses, as well as in some industrial silver plating processes. The compo ...
. * Mesuximide.


Sulfonamides

*
Acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), urine alkal ...
(1953). * Sultiame. * Methazolamide. *
Zonisamide Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease. Chemically it is a sulfonamide. It serves as an anticonvulsant used primarily as an adjunctive therapy ...
(2000).


Triazines

* Lamotrigine (1990).


Ureas

*
Pheneturide Pheneturide ( INN, BAN) (brand names Benuride, Deturid, Pheneturid, Septotence, Trinuride), also known as phenylethylacetylurea (or ethylphenacemide), is an anticonvulsant of the ureide class. Conceptually, it can be formed in the body as a metabo ...
. *
Phenacemide Phenacemide (INN, BAN) (brand name Phenurone), also known as phenylacetylurea, is an anticonvulsant of the ureide (acetylurea) class. It is a congener and ring-opened analogue of phenytoin (a hydantoin), and is structurally related to the barb ...
.


Valproylamides

*
Valpromide Valpromide (marketed as Depamide by Sanofi-Aventis) is a carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorder Affect, in psychology, refers to the underlying experience of feeling, emotion ...
. *
Valnoctamide Valnoctamide ( INN, USAN) has been used in France as a sedative-hypnotic since 1964. It is a structural isomer of valpromide, a valproic acid prodrug; unlike valpromide, however, valnoctamide is not transformed into its homologous acid, valnoct ...
.


Other

*
Perampanel Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai Co. that is used in addition to other drugs to treat partial seizures and generalized tonic-clonic seizures for people older than twelve years. ...
. *
Stiripentol Stiripentol, sold under the brand name Diacomit, is an anticonvulsant medication used for the treatment of Dravet syndrome - a serious genetic brain disorder. The most common side effects include loss of appetite, weight loss, insomnia (difficu ...
. * Pyridoxine (1939).


Non-pharmaceutical anticonvulsants

The
ketogenic diet The ketogenic diet is a high- fat, adequate-protein, low-carbohydrate dietary therapy that in conventional medicine is used mainly to treat hard-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than ca ...
and
vagus nerve stimulation Vagus nerve stimulation (VNS) is a medical treatment that involves delivering electrical impulses to the vagus nerve. It is used as an add-on treatment for certain types of intractable epilepsy and treatment-resistant depression. Medical use VNS ...
are alternative treatments for epilepsy without the involvement of pharmaceuticals. However, both of them can cause severe adverse effects. The adverse effects of vagus nerve stimulation are more severe, and its efficacy is questionable in comparison to medications or the ketogenic diet.


Treatment guidelines

According to guidelines by the
American Academy of Neurology The American Academy of Neurology (AAN) is a professional society representing over 38,000 neurologists and neuroscientists. As a medical specialty society it was established in 1948 by A.B. Baker of the University of Minnesota to advance the ...
and
American Epilepsy Society The American Epilepsy Society (AES) is a nationwide 501(c)(3) non-profit organization for medical professionals and scientific investigators dedicated to finding the prevention, treatment, and cure of epilepsy. History AES was founded in 1946 ...
,AAN Guideline Summary for Clinicians – Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New Onset Epilepsy
Retrieved on 29 June 2010
mainly based on a major article review in 2004, patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such as
carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
,
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
,
valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
/
valproate semisodium Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in thos ...
,
phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...
, or on the newer anticonvulsants
gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabeti ...
, lamotrigine,
oxcarbazepine Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with ...
or
topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...
. The choice of anticonvulsants depends on individual patient characteristics. Both newer and older drugs are generally equally effective in new onset epilepsy. The newer drugs tend to have fewer side effects. For newly diagnosed
partial Partial may refer to: Mathematics * Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial ...
or mixed seizures, there is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate as
monotherapy Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...
. Lamotrigine can be included in the options for children with newly diagnosed
absence seizures Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized b ...
.


History

The first anticonvulsant was
bromide A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retardant ...
, suggested in 1857 by the British gynecologist
Charles Locock Sir Charles Locock, 1st Baronet (21 April 1799 – 23 July 1875) was an obstetrician to Queen Victoria. He is also credited with the introduction of potassium bromide as a treatment for epilepsy. Charles Locock was born to Henry Locock and his w ...
who used it to treat women with "hysterical epilepsy" (probably '' catamenial epilepsy''). Bromides are effective against epilepsy, and also cause
impotence Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of mal ...
, 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.
Phenobarbital Phenobarbital, also known as phenobarbitone or phenobarb, sold under the brand name Luminal among others, is a medication of the barbiturate type. It is recommended by the World Health Organization (WHO) for the treatment of certain types of ep ...
was 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 of
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
by Tracy Putnam and H. Houston Merritt, which had the distinct advantage of treating epileptic seizures with less sedation. By the 1970s, a
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
initiative, 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

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. In recent years, the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
has approved drugs throughout the
European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
. Some of the drugs are no longer marketed.


Pregnancy

During
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, the metabolism of several 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. Therefore, these drugs should be monitored during use in pregnancy. Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbitol, gabapentin have been reported to cause increased risk of
birth defect A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities ca ...
s. Among anticonvulsants, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects. The risk of untreated epilepsy is believed to be greater than the risk of adverse effects caused by these medications, necessitating continuation of antiepileptic treatment.
Valproic acid Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
, and its derivatives such as
sodium valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
and
divalproex sodium Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in thos ...
, causes
cognitive deficit Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process. The term may describe * deficits in overall intelligence (as with intellectual disabilities), * specific and restricted defic ...
in the child, with an increased dose causing decreased
intelligence quotient An intelligence quotient (IQ) is a total score derived from a set of standardized tests or subtests designed to assess human intelligence. The abbreviation "IQ" was coined by the psychologist William Stern for the German term ''Intelligen ...
. On the other hand, evidence is conflicting for
carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure. Similarly, children exposed lamotrigine or
phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
in the womb do not seem to differ in their skills compared to those who were exposed to carbamazepine. There is inadequate evidence to determine if newborns of women with epilepsy taking anticonvulsants have a substantially increased risk of
hemorrhagic disease of the newborn Vitamin K deficiency bleeding (VKDB) of the newborn, previously known as haemorrhagic disease of the newborn, is a rare form of bleeding disorder that affects newborns and young infants due to low stores of vitamin K at birth. It commonly presents ...
. Regarding
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
, some anticonvulsants probably pass into breast milk in clinically significant amounts, including primidone and levetiracetam. On the other hand, valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. 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. Pregnancy planning is being explored as a method that could decrease the risk of possible birth defects. 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. In animal models, several anticonvulsant drugs have been demonstrated to induce neuronal apoptosis in the developing brain.


References


Further reading

* Anti epileptic activity of novel substituted fluorothiazole derivatives by Devid Chutia, RGUHS


External links


eMedicine: Antiepileptic Drugs: an overview

NINDS: Anticonvulsant Screening Program

Use of Anticonvulsants in Pharmacotherapy of Bronchial Asthma



Miami Children's Brain Institute – Anticonvulsants




{{Authority control Epilepsy