By: Aya Alrmah
Carbamazepine is the first-line drug for a type of seizure known as focal tonic-clonic seizure. This seizure is characterized by states of stiffness (tonic) followed by jerking of the muscles (clonic). Carbamazepine is indicated for the treatment of focal tonic-clonic seizures, those originating from one part of the brain, as well as primary and secondary tonic-clonic seizures. Primary tonic-clonic seizures affect both sides of the brain hemispheres, while secondary tonic-clonic seizures originate from a focal point in the brain and spread to other regions (Joint Formulary Committee, 2025).
This antiepileptic drug (AED) can also provide pain relief without any undesirable opioid effects, as it is a non-narcotic analgesic (National Center for Biotechnology Information, 2025). However, due to its narrow therapeutic window, Carbamazepine is a highly regulated and monitored drug and should not be used for common pain relief.
The starting dosage for adults is an initial 100 to 200 mg orally, which is then gradually increased every two weeks in steps of 100 to 200 mg until the final dosage of 0.8 to 1.2g is reached.
Children from the ages of 1 month to 11 years can be prescribed 5mg/kg once daily at night. This dose may be increased in steps of 2.5 to 5 mg/kg every 3 to 7 days as required. The dosage may be increased to 20 mg/kg daily if necessary.
For children from the ages of 12 to 17 the initial dose is 100 to 200 mg 1 to 2 times a day and can be increased to 1.8 g daily if necessary (Joint Formulary Committee, 2025). As with all AEDs, the final dose should never be given before the body has been accustomed to the drug, as well as never abruptly stopping the intake of any AED. If your doctor has deemed it necessary for you to stop your intake, a gradual decrease will be adopted but never stopped immediately.
It should be noted that Carbamazepine is only indicated for focal and generalized tonic-clonic seizures in children, and not for absence seizures, which are characterized by brief loss and return of consciousness (Joint Formulary Committee, 2025).
We now understand that Carbamazepine can help reduce the symptoms of different types of tonic-clonic seizures, but how does it work inside the body?
Seizures are caused primarily by an increase in electrical activity in different areas of the brain. Carbamazepine works by binding to the site of the cell that allows for the passage of electricity and reducing the excess electrical charges found. A seizure occurs when there is minimal regulation at these sites, and more charge than needed passes through. These sites on the cell are known as voltage-gated sodium channels (VGSC). Carbamazepine is able to reduce the frequency of neuronal firing, thus helping return activity back to normal. VGSC are not the only channels that Carbamazepine binds to, as it also binds to similar channels known as voltage-gated calcium channels. Carbamazepine is able to keep these gates in their inactivated state for longer periods, which reduces the firing of the neuron, (Maan JS, et. al., 2023).
We now understand how Carbamazepine affects our bodies and neuronal systems, but what does the human body do to it? This concept is known as Pharmacokinetics, the processes inside the human body that affect and alter drugs that have entered its system. There are four key stages in this process; absorption, distribution, metabolism, and excretion.
The absorption of this AED is fairly complete, meaning most of the drug ingested will be absorbed into the bloodstream. This could be due to its high protein affinity, as it has a strong tendency to bind to proteins found in the blood. Around 75 – 80% of it will be bound to plasma proteins, Res (2013). This is important as Carbamazepine is intended to travel across a web of semipermeable membranes, known as the blood-brain barrier. This allows Carbamazepine to stay in the blood until it reaches its destination, the brain.
Carbamazepine’s affinity towards plasma proteins, however, has its dangers. In mothers, this AED can easily cross through the placenta, and into the fetus’s system. This can be detrimental to the development and health of the newborn (Bertilsson L, 1978).
Once the therapeutic effect has taken its course, it’s time for the body to metabolize the drug in preparation for excretion. Carbamazepine is metabolized through a chemical process of oxidation. For the drug to leave the body it must undergo chemical reactions that make the drug more polar, this creates a region of the molecule that is more positive, while another region in the same molecule is more negative. This polarity allows for the molecule to be excreted instead of reabsorbed into the body. The higher the electrical difference between two areas on a molecule, the more polar it is, which makes its excretion from the body possible.
Once the drug has been metabolized and prepared for excretion, it travels through the kidneys and is filtered out into the urine and out of the body.
Carbamazepine has been used for decades to treat multiple neuronal disorders including epilepsy and has been a life-changing discovery for millions around the world. However, as with any medication, there are possible side effects and complications.
Some common side effects include dizziness, nausea, gastrointestinal discomfort, headaches, and fatigue (Joint Formulary Committee, 2025). If side effects become problematic or persistent, it is always advisable to consult with your healthcare provider.
In some rarer occurrences, certain dermatological reactions may occur. This rare condition is known as Stevens-Johnson syndrome and is usually caused by certain medications including Carbamazepine. If symptoms including fever, rashes, or sores develop, then it is best to get medical attention immediately. Although the condition is serious, it should not stop you from taking the medication you need as cases are rare (National Health Service, 2022).
Patients with Han Chinese ancestry are more susceptible to this condition due to the HLA-B*1502 gene. Any side effects will appear in the first few months of treatment for most patients. People of Japanese, Korean, and European ancestry may also be susceptible due to the HLA*3101 (Gene, Maan JS, 2023).
Carbamazepine is a drug that has greatly improved the quality of life for people all over the world. With its relative acceptance and ability to treat a large portion of patients, it is still used as a first-line agent for different types of epilepsy. It is advised to look out for symptoms that may indicate issues with the liver, blood, or skin; such as rashes, fever, mouth ulcers, or bleeding, and to get medical attention as soon as possible (Joint Formulary Committee, 2025). For a more in-depth overview of Carbamazepine, check out the resources down below.
References:
Bertilsson L. Clinical pharmacokinetics of carbamazepine. Clin Pharmacokinet. 1978 Mar-Apr;3(2):128-43. doi: 10.2165/00003088-197803020-00003. PMID: 346287.
Joint Formulary Committee. (2025). British National Formulary. Retrieved February 13, 2025, from https://bnf.nice.org.uk/drugs/carbamazepine/#indications-and-dose
Maan JS, Duong TvH, Saadabadi A. Carbamazepine. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482455/
National Health Service (2022). Stevens- Johnson Syndrome. National Health Services UK. Retrieved from:, https://www.nhs.uk/conditions/stevens-johnson-syndrome/
PubChem Compound Summary for CID 2554, Carbamazepine. Retrieved February 13, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/Carbamazepine.
