Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study.

OBJECTIVE: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). METHODS: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. RESULTS: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. CONCLUSIONS: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.

Population pharmacokinetics of carbamazepine in adults with epilepsy.

STUDY OBJECTIVE: To conduct a population pharmacokinetic analysis of carbamazepine (CBZ). DESIGN: Retrospective chart review. SETTING: Ambulatory neurology clinics at three medical centers. PATIENTS: Patients diagnosed with epilepsy from 1991-1995. The index set included 829 adults receiving CBZ. A separate validation set consisted of 50 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Final regression equations were apparent oral clearance (Cl/F) (L/hr) = (0.0134 x TBW + 3.58), x 1.42 if receiving phenytoin only; x 1.17 if receiving phenobarbital or felbamate; x 1.62 if receiving phenytoin and phenobarbital or felbamate; x 0.749 if age > or = 70 years; apparent volume of distribution (Vd/F) (L) = 1.97 x total body weight; absorption rate constant [hr(-1)] = 0.441. Interindividual variability in Cl/F and Vd/F was 26% and 82%, respectively. Residual variability was 1.8 mg/L. Predictive performance analysis of the validation set provided a mean prediction error of 0.6 mg/L and median absolute error of 2.4 mg/L. CONCLUSIONS: These routinely collected data provided quantitative estimates of changes in CBZ Cl/F due to comedication and an age-related decrease in Cl/F The derived regression equations reasonably predicted concentrations in a separate validation set.