Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain.[3][4] It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder.[5][4] Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures.[6] It is not effective for absence or myoclonic seizures.[4]
Carbamazepine was discovered in 1953 by Swiss chemist Walter Schindler.[7][8] It was first marketed in 1962.[9] It is available as a generic medication.[10] It is on the World Health Organization's List of Essential Medicines.[11] In 2023, it was the 185th most commonly prescribed medication in the United States, with more than 2million prescriptions.[12][13]
Photoswitchable analogues of carbamazepine have been developed to control its pharmacological activity locally and on demand using light (photopharmacology), with the purpose of reducing the adverse systemic effects of the drug.[14] One of these light-regulated compounds (carbadiazocine, based on a bridged azobenzene or diazocine) has been shown to produce analgesia with noninvasive illumination in vivo in a rat model of neuropathic pain.
Medical uses
Carbamazepine is typically used for the treatment of seizure disorders and neuropathic pain.[4] It is used off-label as a second-line treatment for bipolar disorder and in combination with an antipsychotic in some cases of schizophrenia when treatment with a conventional antipsychotic alone has failed.[4][15] However, evidence does not support its usage for schizophrenia.[16] It is not effective for absence seizures or myoclonic seizures.[4] Although carbamazepine may have a similar effectiveness (as measured by people continuing to use a medication) and efficacy (as measured by the medicine reducing seizure recurrence and improving remission) when compared to phenytoin and valproate,[6]
Adverse effects
In the US, the label for carbamazepine contains warnings concerning:[3]
Common adverse effects may include drowsiness, dizziness, headaches and migraines, ataxia, nausea, vomiting, and/or constipation. Alcohol use while taking carbamazepine may lead to enhanced depression of the central nervous system.[25] Less common side effects may include increased risk of seizures in people with mixed seizure disorders,[29] abnormal heart rhythms, blurry or double vision.[25] Also, rare case reports of an auditory side effect have been made, whereby patients perceive sounds about a semitone lower than previously; this unusual side effect is usually not noticed by most people, and disappears after the person stops taking carbamazepine.[30]
Interactions
Carbamazepine has a potential for drug interactions.[36] Drugs that decrease breaking down of carbamazepine or otherwise increase its levels include erythromycin,[37] cimetidine, propoxyphene, and calcium channel blockers.[36] Grapefruit juice raises the bioavailability of carbamazepine by inhibiting the enzyme CYP3A4 in the gut wall and in the liver.[25] Lower levels of carbamazepine are seen when administered with phenobarbital, phenytoin, or primidone, which can result in breakthrough seizure activity.
Valproic acid and valnoctamide both inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of the active metabolite carbamazepine-10,11-epoxide into inactive metabolites.[38]
Pharmacology
Mechanism of action
Carbamazepine is a sodium channel blocker.[42] It binds preferentially to voltage-gated sodium channels in their inactive conformation, which prevents repetitive and sustained firing of an action potential. Carbamazepine has effects on serotonin systems but the relevance to its antiseizure effects is uncertain. There is evidence that it is a serotonin releasing agent and possibly even a serotonin reuptake inhibitor.[43][44][45] It has been suggested that carbamazepine can also block voltage-gated calcium channels, which will reduce neurotransmitter release.[46]
History
Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953.[49][50] It was first marketed as a drug to treat epilepsy in Switzerland in 1963 under the brand name Tegretol; its use for trigeminal neuralgia (formerly known as tic douloureux) was introduced at the same time.[49] It has been used as an anticonvulsant and antiepileptic in the United Kingdom since 1965, and has been approved in the United States since 1968.[4]
Carbamazepine was studied for bipolar disorder throughout the 1970s.[51]
Society and culture
Environmental impact
Carbamazepine and its bio-transformation products have been detected in wastewater treatment plant effluent[52] and in streams receiving treated wastewater.[53] Field and laboratory studies have been conducted to understand the accumulation of carbamazepine in food plants grown in soil treated with sludge, which vary with respect to the concentrations of carbamazepine present in sludge and in the concentrations of sludge in the soil. Taking into account only studies that used concentrations commonly found in the environment, a 2014 review concluded that "the accumulation of carbamazepine into plants grown in soil amended with biosolids poses a de minimis risk to human health according to the approach."[52]
Brand names
Carbamazepine is available worldwide under many brand names including Tegretol.
Further reading
External links
- Carbamazepine. UK National Health Service
References
- Intravenous carbamazepine: a new formulation of a familiar drug Expert Review of Neurotherapeutics, September 2017^
- Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Diário Oficial da União, 31 March 2023, retrieved 16 August 2023^
- Tegretol- carbamazepine suspension Tegretol- carbamazepine tablet Tegretol XR- carbamazepine tablet, extended release