A multicenter, outpatient, open-label study to evaluate the dosing, effectiveness, and safety of topiramate as monotherapy in the treatment of epilepsy in clinical practice.
ABSTRACT This 24-week, multicenter, open-label trial was designed to evaluate the dosing, effectiveness, and safety of topiramate monotherapy for epilepsy and to identify patient and clinical characteristics predictive of optimally effective stabilized monotherapy doses. Of 406 randomized patients, 244 comprised the evaluable-for-efficacy population (12 weeks of treatment and stabilized topiramate dose during final 28 days); 213 were on topiramate monotherapy at the end of the trial. The mean stabilized daily dose of topiramate over the last 28 days of treatment (primary endpoint) was significantly lower for patients reporting one to three seizures (low seizure frequency, n=147) than for those reporting more than three seizures (high seizure frequency, n=66) during a 3-month retrospective baseline period (191 mg vs 239 mg, P=0.003). Patients in the low-seizure-frequency group reached a stable topiramate dose after a median of 36 days, compared with 53 days for patients in the high-seizure-frequency group. Linear and stepwise regression analyses showed baseline seizure frequency and lifetime seizure count to be significant (P<0.05) predictors of the stabilized dosage. Most treatment-emergent adverse events (TEAEs) were mild to moderate; those occurring with cumulative incidence rates >10% in either seizure frequency group were paresthesia, fatigue, anorexia, dizziness, somnolence, headache, and hypoesthesia; 18.2% of patients discontinued topiramate because of a TEAE, 5.1% reported serious TEAEs, and no deaths were reported during the study.
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ABSTRACT: Few randomised controlled trials (RCTs) have been performed in which a second-generation antiepileptic drug (AED) used as monotherapy was compared with placebo or another AED in children (<18 years of age) with epilepsy. We describe the results of the available studies, assess the validity of these results, and give recommendations for optimal study design for AED monotherapy studies in children with epilepsy. Studies were identified using PubMed (Medline), Embase and the Cochrane Library (January 1990-January 2010). All reports were assessed for methodological quality and results were summarised descriptively. Nine RCTs were included. No difference in efficacy and safety between second-generation AEDs and first-generation AEDs in children was detected. Considerable heterogeneity in study design, inclusion criteria and primary endpoints impaired formal meta-analysis and correct interpretation of results. Follow-up periods were between 2 and 104 weeks; the dosage of the tested AEDs varied between studies, with sometimes use of apparent subtherapeutic dosages; in only two studies the method of randomisation was well described, in only three the power calculations; several studies did not use an intention-to-treat analysis. Although from the available studies first- and second-generation AEDs appear to have similar efficacy and safety in children with epilepsy, these trials are inadequate to provide a sufficient evidence base for decision making. Better trials are needed: AEDs should be studied in optimal paediatric doses, power should be sufficient to detect small but clinically relevant differences, and the follow-up period should be long enough. Most important, primary endpoint to be evaluated should be time to treatment failure or retention rate, since these outcomes combine efficacy and safety.Epilepsy research 09/2010; 91(1):1-9. · 2.48 Impact Factor
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ABSTRACT: Fatigue represents a common side effect of several drugs, however, the underlying mechanisms have not been well identified. A depression of the central nervous system (CNS) and/or changes in peripheral processes have been associated with the development of fatigue. Antiepileptic drugs (AEDs), generally decreasing CNS excitability,are used in the treatment of seizures as well as other neurological and psychiatric diseases. Fatigue is certainly a common AEDs's side effect, although a high degree of variability exists depending on both patient's characteristics and the drug used. Here, we delineate the pathophysiological central and peripheral mechanisms by which AEDs may cause fatigue also reviewing the available clinical data in order to assess a possible AEDs rank and highlight each AEDs related risk. It appears that drugs acting on the GABAergic system have the highest incidence (with tiagabine exception) of fatigue followed by Gabapentin and Levetiracetam whereas drugs mainly inhibiting sodium channels (Carbamazepine, Eslicarbazepine, Lamotrigine, Phenytoin and Valproate) have the lowest. However, the dose used, AEDs related side effects and patients' characteristics might influence the degree of fatigue observed.European journal of pharmacology 09/2013; · 2.59 Impact Factor