An antiepileptic, also called an anticonvulsant, is a drug prescribed alone or in combination to treat epilepsy. In what other indications? The pain ? Headache ? What are these drugs? How do they work and what are the risks?
Definition: what is an antiepileptic?
It is a drug that exerts a action on the central nervous system to suppress or reduce the occurrence of epileptic seizures. An antiepileptic also helps reduce the intensity of seizures (alleviates the symptoms) and to limit possible complications. It is a background treatment administered daily.
What is the mode of action of an antiepileptic?
An antiepileptic may have one or more modes of action (varying depending on the molecule). This type of drug acts on neurons via 3 possible mechanisms of action:
► One activation of GABAergic transmission by binding to GABA-A receptors to increase gamma-aminobutyric acid (GABA) levels.
► One blocking glutamatergic transmission to reduce the release of glutamate.
► One blockade of sodium channels (Na+) and T-type calcium channels (Ca2+).
GABA is an inhibitory neurotransmitter (stifles the transmission of nerve signals) and glutamate is an excitatory neurotransmitter (promotes the transmission of these signals).
Indications: when to take an antiepileptic?
An antiepileptic drug is mainly indicated in adults and children for the treatment of generalized epileptic seizures (crises, absences) or associated with Lennox-Gastaut syndrome (rare brain condition) and partial epilepsy. In children, it is prescribed to prevent epileptic seizures linked to fever in the absence of efficacy of a benzodiazepine.
Some antiepileptics have other indications in adults:
► Bipolar Disorder Treatment in the event of a contraindication or intolerance of lithium (mood regulator), but also the prevention of relapses and associated depressive disorders (Lamictal®, Tégrétol®).
► Background preventive treatment for migraine (topiramate)
► Treatment of neuropathic pain (nerve damage causing painful sensations, especially in diabetes or shingles): Tegretol®, Neurontin®, Lyrica®
► Treatment of generalized anxiety disorder : state of excessive worry (Lyrica®)
► Treatment of painful flare-ups trigeminal and glossopharyngeal nerves (Di-hydan®, Tégrétol®)
Benzodiazepines with antiepileptic properties such as Urbanyl® and Valium® (in drops) are also used to treat severe or debilitating anxiety in adults.
What is the list of the main antiepileptics in France?
► First-generation antiepileptics are the oldest, they include: phenytoin (Di-hydan®); ethosuximide (Zarontin®); barbiturates such as primidone (Mysoline®), phenobarbital alone (Gardénal®) or combined with caffeine (Alepsal®); carbamazepine (Tegretol®); sodium valproate (Dépakine®, Dépakine chrono®, Micropakine®) and its derivatives (Dépamide® and Dépakote®).
► Second-generation antiepileptics, marketed much later, are notably the gabapentin (Neurontin®), the lamotrigine (Lamictal®), the topiramate (Epitomax®).
► The latest specialties placed on the market (after 2000) are classified as second or third generation antiepileptics according to the classifications: brivaracetam (Briviact®); eslicarbazepine (Zebinix®); rufinamide (Inovelon®); lacosamide (Vimpat®); levetiracetam (Keppra®); oxcarbazepine (Trileptal®); pregabalin (Lyrica®); perampanel (Fycompa®); stiripentol (Diacomit®); zonisamide (Zonegran®). Some benzodiazepines have antiepileptic properties like clonazepam (Rivotril®), clobazam (Urbanyl®) for the 10 mg and 20 mg dosages, diazepam (Valium®) in drops or in solution for injection, and midazolam (Buccolam®). The choice of the molecule prescribed depends on several criteria: age and sex of the patient, type of epilepsy, adverse effects, existence of an associated disease. If an antiepileptic alone is ineffective, it can be combined with one or more antiepileptics.
What are non-prescription antiepileptics?
All antiepileptics are available only on presentation of a medical prescription.
What are the side effects of antiepileptics?
The side effects of antiepileptics are numerous and vary depending on the molecule. First-generation antiepileptics are frequently responsible for the following effects:
- liver damage (increased liver enzymes)
- nausea and vomiting
- headache
- dizziness and drowsiness
- skin damage (eruptions)
Some of them cause visual disturbances that are characterized by blurred vision. Other effects are specific to certain drugs. This is the case of gingival hypertrophy induced by phenytoin and the occurrence of edema associated with weight gain with Tegretol®. More rarely with sodium valproate and its derivatives, serious or even fatal liver damage has been observed in the first 6 months of treatment. For this reason, monitoring of liver function will be carried out before initiating treatment and then regularly during the risk period. The side effects frequently reported with recent antiepileptics are:
- dizziness, fatigue, drowsiness, visual disturbances, headache
- digestive disorders (nausea, vomiting, diarrhea)
Most of these drugs can cause Rashes. More rarely, liver damage have been listed. Apart from Lamictal®, all these drugs increase the risk of anxiety or even depression. The drugs Keppra®, Neurontin®, Lyrica® and Briviact® can cause infections such as nasopharyngitis, pharyngitis or otitis. In addition, edema are sometimes observed with Zonegran®, Lyrica® and Neurontin®. Likewise tinnitus have been reported with Vimpat®. Benzodiazepines with antiepileptic properties have the same common side effects as benzodiazepines in general. To know, drowsiness, blurred vision, muscle weakness, increased risk of respiratory depression and fallsetc.
What are the contraindications of antiepileptics?
► All antiepileptics are contraindicated in case of allergy to any component of the drug. More specifically, Di-Hydan® and Gardenal® should not be administered in case wheat allergy (other than gluten intolerance).
► Furthermore, the drugs Mysoline®, Alepsal® and Gardenal® should not be taken by a patient with porphyria (a rare hereditary disease) or severe respiratory failure.
► Similarly, Tegretol®, Zebinix® and Vimpat® should be avoided in case of atrioventricular block (disorder of electrical conduction between the atria and the ventricles of the heart).
► In addition, Zonegran® must not be administered to a patient with peanut or soy allergy.
► The main contraindications for valproate are a hepatitis (acute or chronic), a history of severe hepatitis and an inherited genetic liver disease.
► Benzodiazepines are contraindicated in case of severe respiratory failure, sleep apnea, hepatic failure, myasthenia gravis (disease that weakens the muscles). More specifically Rivotril® should be avoided in case of addiction (drugs, medication, alcohol). In addition, Valium® is contraindicated in cases of galactose intolerance, lactase deficiency (enzymes that help digest milk) and trubles of intestinal absorption.
► The other antiepileptics (Keppra®, Trileptal®, Lamictal®, etc.) have no specific contraindications.
► Note that Di-Hydan®, Alepsal®, Gardenal and Tégrétol® reduce the concentrations of certain medications and increase the risk of ineffectiveness. In a woman of childbearing age, the choice of contraceptive means is made in consultation with the doctor because several antiepileptics can reduce the effectiveness of certain pills. In general, antiepileptics should not be combined with St. John’s wort (natural antidepressant) at the risk of reducing their effectiveness.
► Currently, it turns out that several antiepileptics are associated with a high risk of malformations and developmental disorders of the nervous system in the embryo or fetus. This is the case for the following molecules: valproate, topiramate, phenobarbital, primidone, carbamazepine, phenytoin and pregabalin. The doctor will assess the benefit-risk balance before prescribing an antiepileptic. If a treatment is essential, the choice of treatment will be made among the other existing molecules. In the absence of studies on these drugs, regular medical supervision will be carried out throughout pregnancy.
What are natural antiepileptics?
Several studies suggest the effectiveness of certain natural products in the reduction of epileptic seizures. This is particularly the case of the valerian, omega-3 (in the form of food supplements or in food: oily fish, vegetable oils), magnesium, vitamin Dor even resveratrol (antioxidant contained in red vine). Due to insufficient scientific data, these substances are not recognized in this indication by the public health authorities in France. Note that an epileptic patient taking these natural products must always have regular medical follow-up and continue with medication prescribed by a physician.
Sources:
– Public drug database
– Antiepileptics and pregnancyANSM, 06/30/2022
– Antiepileptics during pregnancy: Current state of knowledge on the risks of malformations and neurodevelopmental disorders, ANSM10/29/202
– Anti-epileptics: the essential points, Pharmacomédicale.org