Anticonvulsants: Uses, common brands, and safety information
Anticonvulsants are commonly used to treat seizure disorders but may also be used to treat other medical conditions, including chronic nerve pain and mental health disorders. There are many different types of anticonvulsants, and they may work in slightly different ways. However, in general, they work by stabilizing nerve cell impulses.
Continue reading to learn more about anticonvulsants, their uses, and their side effects.
- Mebaral (mephobarbital)
- Luminal (phenobarbital)
- Diamox (acetazolamide)
- Carbatrol (carbamazepine)
- Equetro (carbamazepine)
- Oxtellar XR (oxcarbazepine)
- Carnexiv (carbamazepine)
- Depakene (valproic acid)
- Stavzor (valproic acid)
- Depacon (valproic acid)
- Horizant (gabapentin enacarbil)
- Gralise (gabapentin)
- Gaborone (gabapentin)
- Sabril (vigabatrin)
- Fanatrex (gabapentin)
- Diacomit (stiripentol)
- Phenytek (phenytoin)
- Peganone (phenytoin)
- Mesantoin (mephenytoin)
- Cerebyx (fosphenytoin)
- Finetelpla (fenfluramine)
- Epidiolex (cannabidiol)
- Potiga (ezogabine)
- Tridione (trimethadione)
- Briviact (brivaracetam)
- Spritam (levetiracetam)
- Roweepra (levetiracetam)
- Zarontin (ethosuximide)
- Celontin (methsuximide)
- Fycompa (perampanel)
- Klonopin (clonazepam)
- Versed (midazolam)
- Felbatol (felbamate)
- Xcopri (cenobamate)
- Mysoline (primidone)
- Onfi (clobazam)
- Ativan (lorazepam)
- Tranxene-T (clorazepate)
- Banzel (rufinamide)
- Trokendi XR (topiramate)
What are anticonvulsants?
Anticonvulsants, also known as anti-seizure or antiepileptic drugs (AEDs), are medications that calm and regulate nerve impulses and transmission. Because of their nerve-calming actions, anticonvulsants can often be used to treat a variety of medical conditions. Although they are a standard treatment of epilepsy, anticonvulsants can also be used to treat migraines, neuropathic pain, and mental health disorders, such as bipolar disorder. There are many different categories of anticonvulsants that have different mechanisms of action. Not all anticonvulsants work the same, and certain anticonvulsants are prescribed depending on the condition being treated.
How do anticonvulsants work?
Anticonvulsants differ in how they work; however, in general, anticonvulsants work by decreasing excitation or increasing inhibition of nerve activity. In other words, anticonvulsants help calm nerve impulses and decrease how easily those impulses are activated. Nerve cells that might otherwise fire rapidly during a seizure are kept under control.
Anticonvulsants can act as mood stabilizers to treat mental health disorders, migraines, and other brain disorders. Anticonvulsants can also reduce the transmission of pain signals from overly sensitive or damaged nerves to help relieve pain from conditions like diabetic neuropathy, trigeminal neuralgia, and postherpetic neuralgia.
What are anticonvulsants used for?
Anticonvulsants are FDA-approved and sometimes used off-label to manage different medical conditions:
Types of anticonvulsants
AMPA receptor antagonists
AMPA receptors are glutamate receptors involved with excitatory nerve activity. AMPA receptor antagonists block these receptors to reduce and stabilize nerve activity. These medicines can be used to treat partial seizures in patients with epilepsy. An example of an AMPA receptor antagonist is Fycompa (perampanel).
Barbiturates work by increasing the activity of a neurotransmitter known as gamma-aminobutyric acid (GABA), which is an inhibitory neurotransmitter responsible for slowing down electrical activity in the brain. Barbiturate anticonvulsants can treat all seizures except for a specific type of seizure known as an absence seizure. Mysoline (primidone), Mebaral (mephobarbital), and Luminal (phenobarbital) are in the barbiturate category.
Benzodiazepines act on GABA-A receptors and increase the activity of GABA neurotransmitters. Benzodiazepines may be used to treat febrile seizures, partial and generalized seizures, acute repetitive seizures, alcohol withdrawal seizures, and status epilepticus. Benzodiazepines may also be used as anti-anxiety or sedative medicines. Examples of benzodiazepines include Klonopin (clonazepam), Ativan (lorazepam), and Valium (diazepam).
The exact way in which carbamate anticonvulsants work is unknown, but they are believed to inhibit NMDA receptors while increasing GABA activity. Because these medications carry a risk of potentially serious side effects, such as aplastic anemia, hepatitis, and liver failure, they are only used after trying other anticonvulsant options first. Examples of carbamate anticonvulsants include Felbatol (felbamate) and Xcopri (cenobamate).
Carbonic anhydrase inhibitor anticonvulsants
Carbonic anhydrase inhibitors work by inhibiting the carbonic anhydrase enzyme. These medications can treat epilepsy, migraines, glaucoma, and mountain sickness. Examples of carbonic anhydrase inhibitors include Diamox (acetazolamide) and Zonegran (zonisamide).
Dibenzazepine anticonvulsants work by blocking voltage-gated sodium channels, which are involved in the transmission of nerve signals. These medications can decrease the severity and frequency of seizures. Dibenzazepine anticonvulsants are also used to treat bipolar disorder and schizophrenia. Aptiom (eslicarbazepine) is an anticonvulsant approved as an adjunctive treatment for partial-onset seizures. Other examples of benzodiazepines include Tegretol (carbamazepine) and Trileptal (oxcarbazepine).
Fatty acid derivative anticonvulsants
Fatty acid derivative anticonvulsants work by increasing the activity of GABA. These medicines also block sodium and calcium channels, which helps slow nerve activity that can otherwise result in seizures. Fatty acid derivatives are useful for most seizure types. They may be given to treat absence seizures, tonic-clonic seizures, juvenile myoclonic epilepsy, and complex partial seizures. Additionally, these medications may be used to treat bipolar disorder, migraines, and schizophrenia. Examples of fatty acid derivatives include Depakote (divalproex) and Depakene (valproic acid).
GABA analogs are medicines that have a structure very similar to GABA. These medicines can stabilize the nervous system and reduce impulses that could trigger seizure activity. GABA analogs are given for seizures, epilepsy, fibromyalgia, neuropathic pain, and restless leg syndrome. Examples of medications in this category include Lyrica (pregabalin), Neurontin (gabapentin), and Sabril (vigabatrin).
GABA reuptake inhibitors
GABA reuptake inhibitors are another category of seizure medications that increase the availability of GABA in the brain. These medicines increase GABA activity by binding to and blocking transporters that reabsorb GABA. GABA reuptake inhibitors are used to treat different types of seizures. Examples of GABA reuptake inhibitors include Gabitril (tiagabine) and Diacomit (stiripentol).
Hydantoin anticonvulsants work by blocking sodium channels and slowing nerve impulses through these channels. Hydantoin anticonvulsants are used to treat many different types of seizures. Examples of hydantoin anticonvulsants include Dilantin (phenytoin), Peganone (ethotoin), and Sesquient (fosphenytoin).
Neuronal potassium channel openers
Neuronal potassium channel openers help decrease the excitability of nerve cells. They work by activating potassium channels. Potiga (ezogabine) is a neuronal potassium channel opener.
The mechanism of action for oxazolidinedione anticonvulsants is unknown, but they are effective in treating absence seizures. An example of an oxazolidinedione anticonvulsant is Tridione (trimethadione).
Pyrrolidine anticonvulsants work by slowing the transmission of nerve signals. The exact mechanism of action of these anticonvulsants is unknown. They are typically used as adjunctive treatments for tonic-clonic and partial seizures. Examples of pyrrolidine anticonvulsants are Keppra (levetiracetam) and Briviact (brivaracetam).
Succinimide anticonvulsants inhibit calcium channels and increase the seizure threshold. The seizure threshold refers to the strength of an impulse that will trigger a seizure. The higher the seizure threshold, the less likely a seizure is to occur. Succinimide anticonvulsants are primarily used to treat absence seizures. Examples of succinimide anticonvulsants include Zarontin (ethosuximide) and Celontin (methsuximide).
Triazine anticonvulsants work on sodium channels and inhibit the release of glutamate and aspartate, which are neurotransmitters that excite the nervous system. These medications treat seizures, partial seizures, tonic-clonic seizures, bipolar disorder, and schizophrenia. Lamictal (lamotrigine) is a triazine anticonvulsant.
Who can take anticonvulsants?
Adults with epilepsy, bipolar disorder, and other neurological conditions can safely take anticonvulsants. Anticonvulsant agents given as monotherapy may be sufficient to control symptoms, however, multiple anticonvulsants may be needed to achieve the desired effect.
Doses of anticonvulsants vary and need to be closely monitored or adjusted. Some medications require blood tests to monitor the blood levels of the drug. Doses may need to be adjusted based on liver or kidney function.
Many seizure medicines must be maintained at a certain blood level. For this reason, it is essential to make sure doses are not missed. Missed doses may cause drug levels to fall, which could result in an increased risk of seizure activity.
The Food and Drug Administration (FDA) has approved anticonvulsants to treat seizure disorders and migraine headaches in children. However, not every drug is approved for every type of pediatric seizure disorder.
Drug levels of certain medications may need to be monitored. It is critical to avoid missed doses of medication to maintain proper blood levels of medication. The dosing of anticonvulsants in children is usually calculated according to weight. Many anticonvulsant medications are available in liquid form for easier administration in children.
Seniors may safely take anticonvulsants with proper monitoring. Doses may be adjusted if the particular person has decreased kidney or liver function. Some medications may require regular monitoring of drug levels in the blood, and it is important to avoid missed doses.
Because seniors are often taking other medications with an anticonvulsant, prescribers should consider potential drug interactions. Seniors may be more sensitive to experiencing sedation from anticonvulsants. They may also have an increased fall risk with certain anticonvulsants. Seniors may need to be monitored carefully for any possible adverse effects from anticonvulsants.
Are anticonvulsants safe?
In general, anticonvulsants, when monitored appropriately, are safe. However, certain groups of people should not take certain anticonvulsants.
Tell your doctor if you have a history of the following before taking an anticonvulsant:
- Any drug allergies
- Kidney disease
- Liver disease
- Use of other medications
Black box warnings
Carbamazepine carries a black box warning for dermatologic conditions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS). These conditions are rare but potentially fatal skin disorders characterized by blistering and peeling of the skin.
Carbamazepine also carries a black box warning for aplastic anemia and agranulocytosis. These conditions are characterized by decreased blood cell counts. Lab tests may need to be evaluated before starting carbamazepine and monitored throughout therapy.
Felbamate carries a black box warning for aplastic anemia and liver failure. Blood testing should be performed before starting therapy and monitored throughout treatment with Felbamate.
Serious skin rashes, including SJS, are listed in a black box warning for lamotrigine. Lamotrigine should be discontinued if a rash develops.
Perampanel carries a black box warning for serious psychiatric and behavioral reactions. A patient taking perampanel should be monitored for aggression, hostility, irritability, anger, and homicidal ideation. If these behaviors develop, the medication should be discontinued.
Valproic acid and divalproex
Valproic acid and divalproex carry a black box warning for hepatotoxicity, teratogenicity, and pancreatitis. Liver function should be checked before and throughout therapy.
Teratogenicity refers to the effects these medications may have on an unborn child. The potential effects of valproic acid and divalproex include congenital malformations and neural tube defects (spina bifida). Use in pregnancy is not generally recommended, and women are cautioned to avoid becoming pregnant while taking these medications.
Vigabatrin carries a black box warning for vision loss. Patients taking this medication should have their vision tested within four weeks of beginning medication and every three months throughout the duration of therapy.
Those with a known sensitivity or prior allergic reaction should not take an anticonvulsant. Other contraindications to treatment with an anticonvulsant include liver failure, certain blood disorders, narrow-angle glaucoma, and familial short QT syndrome.
Kidney failure or dialysis may require dose adjustments and frequent monitoring of anticonvulsant treatment.
Can you take anticonvulsants while pregnant or breastfeeding?
It is recommended to avoid pregnancy while taking anticonvulsants. However, depending on the drug prescribed, the American Academy of Neurology does not recommend stopping or changing treatment in pregnant women as the risk of breakthrough seizure may be high. Valproic acid should be avoided during pregnancy due to the risk of fetal harm.
Anticonvulsants are found in measurable levels in breastmilk. However, the benefits of continuing medication may outweigh the risk of harm to an infant. Consult a healthcare provider before taking an anticonvulsant while breastfeeding.
Are anticonvulsants controlled substances
Some anticonvulsants are classified as controlled substances. These include:
- Pregabalin: Schedule V
- Lacosamide: Schedule V
- Perampanel: Schedule III
- Clonazepam: Schedule IV
- Diazepam: Schedule IV
- Lorazepam: Schedule IV
- Phenobarbital: Schedule IV
Common anticonvulsants side effects
The most common side effects of anticonvulsants include:
- Low sodium levels
- Fluid retention
- Hair loss
- Weight gain
- Mood changes
- Poor appetite
More severe but rare side effects include:
- Aplastic anemia
- Liver failure
- Stevens-Johnson syndrome
- Blood disorders
- Loss of vision
This list of side effects is not comprehensive. Consult a healthcare provider for a complete list of side effects, warnings, and precautions before starting treatment with an anticonvulsant.
How much do anticonvulsants cost?
Anticonvulsants can vary in price. Brand-name medications may cost considerably more than other drugs that are available in generic forms. Most anticonvulsants are available in brand-name and generic formulations. Medicare plans may only cover specific formulations while other insurance plans may cover most types of anticonvulsants. Costs will vary depending on your insurance plan. Without insurance, the price can vary widely depending on the medication and quantity of medication prescribed. However, using a prescription discount card from SingleCare may help reduce the cost of anticonvulsants.
List of anti-epileptic drugs
Here we list the different AEDs and link to information about what type of seizures they are used for, doses, and possible side effects from either the British National Formulary (BNF), British National Formulary for Children (BNFC), the electronic Medicines Compendium (eMC) or the National Institute for Health and Care Excellence (NICE) clinical guideline for epilepsy (CG137). NICE is an independent organisation that provides national guidance to improve health and social care services in England.
Click on the links below to search for information about AEDs:
- by the generic name of the AED
- by the brand name of the particular type of AED or
- by the type of seizure or seizures you have.
Generic names with brand names
- Brivaracetam available as Briviact
- Cannabidiol available as Epidyolex
- Carbamazepine also available as Tegretol, Tegretol Prolonged Release
- Clobazam also available as Frisium, Perizam, Tapclob, Zacco
- Eslicarbazepine acetate available as Zebinix
- Everolimus also available as Votubia
- Fenfluramine available as Fintepla
- Gabapentin also available as Neurontin
- Lacosamide available as Vimpat
- Lamotrigine also available as Lamictal
- Levetiracetam also available as Desitrend, Keppra
- Oxcarbazepine also available asTrileptal
- Perampanel available as Fycompa
- Phenytoin also available as Epanutin, Phenytoin Sodium Flynn
- Piracetam available as Nootropil
- Pregabalin also available as Alzain, Axalid, Lecaent, Lyrica
- Primidone also available as Liskantin Saft
- Rufinamide available as Inovelon
- Sodium valproate (important information for women here) also available as Epilim,Epilim Chrono,Epilim Chronosphere, Episenta, Epival, Dyzantil
- Stiripentol also available as Diacomit
- Tiagabine available as Gabitril
- Topiramate also available as Topamax
- Valproic acid available as Convulex, Epilim Chrono, Epilim Chronosphere, Dyzantil
- Vigabatrin available as Sabril, Kigabeq
- Zonisamide also available as Zonegran, Desizon
You can find information about which types of seizures different AEDs are used for by following these links to either the NICE guideline, the BNF or, for children the BNFC.
Valproate: Sodium valproate and Valproic acid must not be used in females of childbearing potential unless the conditions of the Pregnancy Prevention Programme are met and alternative treatments are ineffective or not tolerated. During pregnancy, it must not be used for epilepsy unless it is the only possible treatment.
For information on doses and side effects click on the AED name above and this will take you to the electronic Medicines Compendium(eMC), British National Formulary (BNF) or British National Formulary for Children (BNFC)where you can view the patient information leaflet (PIL).
A first line AED is an AED that is tried first. Some AEDs added to a first line AED are called second line AEDs.
AEDs are not split into first and second line for treating children age 12 and under.
Treatment of neonatal seizures (from birth to 28 days of age) is not covered.
‘Effective’ means the seizures it works for. ‘Monotherapy’ means the AED is taken on its own. ‘Adjunctive' or 'Add-on therapy’ means the AED is taken alongside other AEDs. ‘Tolerance’ means that a drug becomes less effective the longer you take it. A 'tertiary epilepsy specialist' is a speciailst with particular expertise and training in epilepsy. 'idiopathic epilepsy' is where someone's epilepsy is genetic or inherited.
Information for this page comes from sources including the British National Formulary (BNF), the British National Formulary for children (BNFC) and the electronic Medicines Compendium (eMC).
Every effort is made to ensure that all information is correct at time of publishing but information may change after publishing. This information is a guide only and is not a substitute for advice from your doctor. Epilepsy Society is not responsible for any actions taken as a result of using this information.
Information updated: August 2021
The aim of treatment is to stop all of your seizures with the lowest dose of the fewest number of AEDs and with the least side effects.
In March 2017 the International League Against Epilepsy (ILAE), a group of the world's leading epilepsy professionals, introduced a new method to group seizures. This gives doctors a more accurate way to describe a person's seizures, and helps them to prescribe the most appropriate treatments.
Class of medications
Anticonvulsants (more commonly known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epilepticseizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Early treatment for neonatal seizures can help in the future. "Neonates presenting seizures should be provided early treatment to minimize mortality and disabilities". The death rate will decrease as well as the life threatening conditions these seizures can have on the infants. “Regarding the potentially toxic effect of AEDs on brain development and the knowledge that neonatal seizures are often controlled within a few days after start of medication warrant a shorter duration of treatment”. AEDs stands for anti-epileptic drug and even though it can have some negative effects on an infant it still is the most efficient in helping treat neonatal seizures. These drugs help take control of the seizures and stop them. They are not a cure for seizures, but they have positive outcomes.
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 and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase. 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.
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 (the development of epilepsy in an individual at risk, such as after a head injury).
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.[medical citation needed]
The usual method of achieving approval for a drug is to show it is effective when compared against placebo, 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 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 and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy.
In the following list, the dates in parentheses are the earliest approved use of the drug.
Main article: Aldehyde
Aromatic allylic alcohols
Main article: Barbiturate
Barbiturates are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. The following are classified as anticonvulsants:
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, diazepam or midazolam is usually tried first. Other barbiturates only have an anticonvulsant effect at anaesthetic doses.
Main article: Benzodiazepine
The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant 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 the many drugs in this class, only a few are used to treat epilepsy:
The following benzodiazepines are used to treat status 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 the buccal mucosa.
- Lorazepam (1972). Given by injection in hospital.
Nitrazepam, temazepam, and especially nimetazepam are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties.
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.
Main article: Carbamate
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 but is better tolerated and is also available generically.
- Eslicarbazepine acetate (2009).
Main article: Fatty acid
The following are fatty-acids:
Vigabatrin and progabide are also analogs of GABA.
Main article: Fructose
Main article: Hydantoin
The following are hydantoins:
Main article: Oxazolidinedione
The following are oxazolidinediones:
Main article: Propionate
Main article: Pyrimidinedione
Main article: Pyrrolidine
Main article: Succinimide
The following are succinimides:
Main article: Sulfonamide (medicine)
Main article: Triazine
Main article: Urea
Main article: Amide
This article is about anticonvulsant drugs. For non-pharmaceutical "anticonvulsants", see Epilepsy § Other treatment.
The ketogenic diet and vagus nerve stimulation 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 it's efficacy is questionable in comparison to medications or the ketogenic diet.
According to guidelines by the American Academy of Neurology and American Epilepsy Society, 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, phenytoin, valproic acid/valproate semisodium, phenobarbital, or on the newer anticonvulsants gabapentin, lamotrigine, oxcarbazepine or topiramate. 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 or mixed seizures, there is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate as monotherapy.Lamotrigine can be included in the options for children with newly diagnosed absence seizures.
The first anticonvulsant was bromide, suggested in 1857 by the British gynecologist Charles Locock who used it to treat women with "hysterical epilepsy" (probably catamenial epilepsy). Bromides are effective against epilepsy, and also cause impotence, 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 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 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 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 has approved drugs throughout the European Union. Some of the drugs are no longer marketed.
During pregnancy, 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 defects. 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, and its derivatives such as sodium valproate and divalproex sodium, causes cognitive deficit in the child, with an increased dose causing decreased intelligence quotient. On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure. Similarly, children exposed lamotrigine or phenytoin 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.
Regarding breastfeeding, 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.
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Name anticonvulsant drugs
.Anticonvulsant drugs structure and IUPAC names Antiepileptic drugs
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