From the FDA Drug Label
DOSAGE AND ADMINISTRATION (see TABLE BELOW) As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level.
The FDA drug label does not answer the question.
From the Research
When weaning a patient with epilepsy off carbamazepine, I recommend reducing the midday dose first. For a patient currently taking 400mg three times daily (morning, midday, and evening), begin by decreasing the midday dose to 300mg while maintaining the morning and evening doses at 400mg. This approach is preferred because maintaining higher blood levels during the overnight period (evening dose) and upon waking (morning dose) provides better seizure protection during vulnerable times, as suggested by the general principles of antiepileptic drug management 1. The midday reduction creates less dramatic fluctuations in blood levels compared to altering the morning or evening doses.
After one week at this regimen, continue the weaning process by reducing the morning dose to 300mg, followed by the evening dose in subsequent weeks, decreasing by 100mg weekly until complete discontinuation. Throughout this process, monitor the patient closely for breakthrough seizures or withdrawal symptoms, and be prepared to slow the tapering schedule if needed, as carbamazepine has a narrow therapeutic window and its pharmacokinetics can be variable 1. This gradual approach minimizes the risk of withdrawal seizures while allowing the brain to adjust to decreasing levels of carbamazepine.
Some studies have investigated the use of carbamazepine in various contexts, including its efficacy in treating generalized tonic-clonic seizures in idiopathic generalized epilepsy 2, and its potential as an adjunctive therapy for benzodiazepine withdrawal syndrome 3. However, these studies do not directly inform the decision of which dose to reduce first when weaning a patient off carbamazepine. The key consideration is to minimize the risk of seizures and withdrawal symptoms while gradually reducing the dose, which is best achieved by reducing the midday dose first.
It's also worth noting that the bioavailability of carbamazepine can vary between different formulations, but this does not affect the approach to weaning off the medication 4. The most important factor is to tailor the weaning schedule to the individual patient's needs and response, and to prioritize their safety and seizure control throughout the process.