Abstracts

RATIONALE: The objective of this study was to determine whether extended-release carbamazepine (ER-CBZ) reduces side effects and seizures compared to therapy with immediate-release carbamazepine (IR-CBZ). Fluctuation in blood concentrations of short-acting anticonvulsants may increase risks for side effects during periods of peak concentrations and of seizure breakthroughs during concentration troughs. Extended-release anticonvulsant formulations may potentially alleviate side effects and reduce seizures associated with daily medication fluctuations
METHODS: We screened all patients who were treated for partial-onset seizures with IR-CBZ while under care at the Johns Hopkins adult epilepsy clinic. Patients were studied if they received IR-CBZ for a one-year study period and then were converted to ER-CBZ.Patients were monitored for one year during ER-CBZ treatment or until treatment was discontinued or new AEDs were initiated. Patients were excluded if they had severe medical or psychiatric disorders, pregnancies, or received epilepsy surgery during study periods. We compared IR-CBZ and ER-CBZ treatment periods for changes in patient self-reporting of side effects and changes in seizure frequencies.
RESULTS: A total of 63 patients switched from IR-CBZ to ER-CBZ: 29 males and 34 females with a mean age of 39 years (range 19-76). Daily carbamazepine doses for the two treatments were the same: IR-CBZ mean, 961 mg + 397 SD; ER-CBZ mean, 989 mg + 341 SD (r = 0.7, p[lt].001). Nineteen patients (30%) converted from IR-CBZ to ER-CBZ for dosing convenience and did not have seizures or side effects. Thirty-one patients (48%) had CNS toxicity during treatment with IR-CBZ (sedation, confusion, dizziness, ataxia, or diplopia); with ER-CBZ treatment, only 16 (25%) had these symptoms (chi-Square = 0.94, p[lt].01). Monthly seizure frequency decreased slightly following conversion from IR-CBZ (median, 1.5 + 0.8 SEM) to ER-CBZ (median 1.0 + 0.7 SEM); however, this difference was not significant (paired t-test, p = 0.2).
CONCLUSIONS: CNS-related side effects are common during treatment with IR-CBZ and are markedly reduced following conversion to ER-CBZ. Seizures are reduced only slightly in a referral epilepsy population (mean number of previous failed AEDs = 2.9) following conversion to ER-CBZ. While many patients switch from IR-CBZ to ER-CBZ for the convenient BID dosing schedule, CNS side effects are a major source of morbidity for patients treated with AEDs and can potentially be reduced using slow-release preparations.
[Supported by: Shire US Inc.]; (Disclosure: Grant - G Krauss, Shire, Consulting - G Krauss, Shire)