[A practical study of the efficacy of a delayed-action preparation of carbamazepine (Tegretol CR 400) in the treatment of patients with partial epilepsy ].
ABSTRACT Carbamazepine (CBZ) is the first choice antiepileptic drug in the treatment of partial seizures. Many clinical studies show high efficacy and good tolerance of CBZ in the majority of patients. However, poor water solubility and erratic absorption as well as autoinduction of its metabolism, cause wide and unpredictable fluctuations in CBZ serum concentration. In order to avoid these problems controlled-release formulations of CBZ (Tegretol CR 400) were developed.
The aim of this study was to evaluate the efficacy, tolerance and practicality of the therapy of partial seizures in adults with controlled-release CBZ (Tegretol CR 400).
Over a three-year period we conducted an open pragmatic study of controlled-release CBZ in the therapy of 141 adult patients with established diagnosis of localized related epilepsy. Patients with progressive brain or systemic disease were excluded. All patients had unacceptable seizure frequency and were divided into four groups: 1) 34 with newly-diagnosed epilepsy; 2) 42 with chronic epilepsy and no previous antiepileptic medication; 3) 27 with chronic epilepsy previously treated with conventional preparations of carbamazepine (CBZ); and 4) 38 with chronic epilepsy previously treated with other antiepileptic medications. Patients were switched to controlled-release CBZ and the dosage was slowly adjusted. Baseline evaluation included the analysis of efficacy, tolerance and practicality of the controlled-release CBZ therapy. Three categories of efficiency were defined: 1) successful (patients without seizures); 2) partially successful (patients with improvement of at least 50% in frequency and severity of seizures); and 3) unsuccessful therapy (same or worse than before controlled-release CBZ). Tolerance and practicity were evaluated through the analysis of side effects and frequency of daily doses, respectively. These variables were compared to the corresponding ones after a period of at least three months of full dosage controlled-release CBZ therapy.
In all four groups the therapy was successful in 76%, 52%, 30% and 29%, partially successful in 18%, 43%, 30% and 32%, and unsuccessful in 6%, S%, 40% and 39%, respectfully. Side effects occurred less frequently in all 4 groups during the therapy with controlled-release CBZ. We found reduced frequency of drug administration (once or twice daily) in 97.9% of our patients.
Due to its slow and irregular absorption, short half life, wide and unpredictable fluctuation in plasma levels CBZ has decreased ability to control seizures, with the appearance of the intermittent side-effects such as diplopia, ataxia, headache and dizziness. Controlled-release formulation of CBZ sustains stable absorption and reduces fluctuations in carbamazepine serum concentration. Steady serum levels permit to the majority of patients to tolerate a higher total daily dose by reducing peak-dependent side-effects and improve compliance as a result of less frequent daily doses (1 or 2).
In patients with partial seizures controlled-release vs. conventional carbamazepine had better efficiency, based on an excellent tolerance, favorable daily dosage and superior compliance.