Carbamazepine is a tricyclic carboxamide with anticonvulsant and analgesic properties. It is commonly used to treat epilepsy, neuropathic pain, and psychotic disorders. Its mechanism of action is believed to be similar to that of phenytoin, which has a similar three-dimensional structure and works as an anticonvulsant by binding to inactive sodium channels. This stops convulsions by preventing post-tetanic potentiation and polysynaptic reflexes.1 Carbamazepine also prevents epileptic seizures by working as GABA receptor agonist.2 The drug’s analgesic properties may be mediated by an ability to act as a serotonin releasing agent and a serotonin reuptake inhibitor.3
Common side effects of carbamazepine include:
Patients should contact a doctor if they experience serious side effects, such as:
Anti-convulsant medications can trigger suicidal thoughts or actions. Patients experiencing depression or other severe mood changes should get help immediately. Patients should not stop taking carbamazepine abruptly, as it can increase the risk of seizures. Patients who are pregnant should not take carbamazepine, as it can cause developmental disorders and congenital malformations in the fetus. The drug also passes into breast milk, so patients who are nursing should talk to a doctor before taking carbamazepine.5
Medications that are CYP3A4 inhibitors inhibit carbamazepine, which leads to an increase in plasma levels of the carbamazepine. These drugs include aprepitant, azoles, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, trazodone, olanzapine, loratadine, terfenadine, omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene, protease inhibitors, and verapamil. Grapefruit juice contains bergamottin, a compound that is also a CYP3A4 inhibitor, so it should be avoided by patients who are taking carbamazepine. Inhibitors of human microsomal epoxide hydrolase, including loxapine, quetiapine, and valproic acid, can also increase plasma levels of carbamazepine.
CYP3A4 inducers increase the rate of carbamazepine metabolism, which lowers its effectiveness. These drugs include cisplatin, doxorubicin HCl, felbamate, rifampin, phenobarbital, phenytoin, primidone, methsuximide, and theophylline.
Because carbamazepine is a CYP450 inducer, it can increase the metabolism of aripiprazole, tacrolimus, temsirolimus, lamotrigine, lapatinib, nefazodone, phenytoin, valproic acid, and warfarin, thereby dampening their effects. Carbamazepine also increases the clearance of many benzodiazepines. Women using hormonal birth control to avoid pregnancy may want to avoid carbamazepine because it can speed metabolism of the hormones in the drug and render it ineffective.6
Carbamazepine was discovered in Switzerland in 1953. It was first marketed in 1963 as a treatment for epilepsy and neuropathic pain. Doctors in Japan began studying the drug’s ability to treat schizophrenia and bipolar disorder in the 1970’s. Today, carbamazepine is the most commonly prescribed antiepileptic drug on the market.7 It is included on the WHO Model List of Essential Medications, a list of the drugs that are considered to be critical for a basic health system.
Recent studies have explored different ways of delivering carbamazepine. The drug is usually taken orally, but the FDA is currently reviewing an intravenous formulation that can be administered to control seizures when epileptic patients are temporarily unable to take the drug by mouth.8 Researchers have also examined the efficacy of controlled-release oral formulations that deliver carbamazepine over a longer period of time. There is no evidence that controlled-release formulations are more effective than immediate-release formulations, but they may reduce adverse side effects.9
Scientists are also studying the environmental impacts of carbamazepine. The drug has been detected in streams across the United States and it may harm aquatic ecosystems.10 It has also been found in wastewater effluent, which is sometimes included in “sludge” that is used irrigate food crops. Studies suggest that this may pose a risk to human health.11