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The assay of saliva samples provides a valuable alternative to the use of blood samples for therapeutic drug monitoring (TDM), at least for certain categories of patients. To determine the feasibility of using saliva sampling for the TDM of rufinamide, we compared rufinamide concentrations in paired samples of saliva and plasma collected from 26 patients with epilepsy at steady state. Within-patient relationships between plasma rufinamide concentrations and dose, and the influence of comedication were also investigated. Assay results in the two tested fluids showed a good correlation (r2 = .78, P

Objective To evaluate the efficacy and safety of adjunctive eslicarbazepine acetate (ESL) in patients with refractory partial-onset seizures. Methods This randomized, placebo-controlled, double-blind, parallel-group, phase III study was conducted at 173 centers in 19 countries, including the United States and Canada. Eligible patients were aged ≥16 years and had uncontrolled partial-onset seizures despite treatment with 1–2 antiepileptic drugs (AEDs). After an 8-week baseline period, patients were randomized to once-daily placebo (n = 226), ESL 800 mg (n = 216), or ESL 1,200 mg (n = 211). Following a 2-week titration period, patients received ESL 800 or 1,200 mg once-daily for 12 weeks. Seizure data were captured and documented using event-entry or daily entry diaries. Results Standardized seizure frequency (SSF) during the maintenance period (primary end point) was reduced with ESL 1,200 mg (p = 0.004), and there was a trend toward improvement with ESL 800 mg (p = 0.06), compared with placebo. When data for titration and maintenance periods were combined, ESL 800 mg (p = 0.001) and 1,200 mg (p

Summary Purpose: To evaluate the relative contribution of demographic and epilepsy-related variables, depressive symptoms, and adverse effects (AEs) of antiepileptic drugs (AEDs) to health-related quality of life (HRQOL) in adults with pharmacoresistant epilepsy. Methods: Individuals with epilepsy whose seizures failed to respond to at least one AED were enrolled consecutively at 11 tertiary referral centers. HRQOL was assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), AEs by the Adverse Event Profile (AEP), and depressive symptoms by the Beck Depression Inventory-II (BDI-II). Multivariate linear regression models were used to identify variables associated with QOLIE-31 total score and subscale scores. Key Findings: Of 933 enrolled individuals aged 16 years or older, 809 (87%) were able to complete the self-assessment instruments and were included in the analysis. Overall, 61% of the variance in QOLIE-31 scores was explained by the final model. The strongest predictors of HRQOL were AEP total scores (β = −0.451, p

Summary Purpose: To evaluate the adverse effects (AEs) of antiepileptic drugs (AEDs) in adults with refractory epilepsy and their relationship with number of coprescribed AEDs and AED load. Methods: Patients with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers. AEs were assessed through unstructured interview and the Adverse Event Profile (AEP) questionnaire. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each coprescribed AED. Results: Of 809 patients enrolled, 709 had localization-related epilepsy and 627 were on polytherapy. AED loads increased with increasing number of AEDs in the treatment regimen, from 1.2 ± 0.5 for patients on monotherapy to 2.5 ± 1, 3.7 ± 1.1, and 4.7 ± 1.1 for those on two, three, and ≥4 AEDs, respectively. The number of spontaneously reported AEs correlated with the number of AEs identified by the AEP (r = 0.27, p

Summary: Purpose: To determine potential changes in total and unbound serum valproic acid (VPA) concentrations at steadystate during a cycle of intake of combined hormonal contraceptive (HC) steroids. Methods: Blood samples were collected from nine women stabilized on VPA monotherapy on two separate randomized occasions: (i) at the end of the 4- to 7-day HC-free interval, and (ii) on the last day of the HC intake period. Trough concentrations of VPA in serum and serum ultrafiltrates were determined by fluorescence polarization immunoassay. Results: In all women, total and unbound VPA concentrations were higher during the HC-free interval than during HC intake (means ± SD: 425 ± 184 vs. 350 ± 145 μmol/L, respectively, for total VPA, p = 0.002, and 55 ± 37 vs. 39 ± 25 μmol/L, respectively, for unbound VPA, p = 0.005). Compared with the HC-free interval, HC intake was associated with a mean 21.5% increase in VPA total apparent oral clearance (from 8.0 ± 5.2 to 9.7 ± 6.4 ml/h/kg, p = 0.01) and a 45.2 % increase in VPA unbound apparent oral clearance (from 79 ± 81 to 115 ± 121 ml/h/kg, p = 0.029). Conclusions: The apparent oral clearance of total and unbound VPA increases during the HC intake period compared with the HC-free interval, probably due to induction of glucuronosyltransferase by ethinylestradiol. The magnitude of the change varies across individuals, being potentially clinically relevant in some cases. Serum VPA concentrations should be monitored when adding or discontinuing HC steroids, and possibly during the on‐off intervals of a HC cycle. Key Words: Valproic acid—Contraceptive steroids— Pharmacokinetics—Drug interaction—Epilepsy.

Summary: Purpose: The aim of this study was to evaluate the rate and features of obstructive sleep apnea (OSA) in adult epilepsy patients. Methods: Two hundred eighty-three adult epilepsy patients (137 men; mean age, 33 years; range, 18‐70 years) were prospectively screened for OSA by means of a structured interview. Those in whom OSA was clinically suspected were monitored for a full night by using a portable device (Polymesam), and OSA was diagnosed when they had an Apnea/Hypopnea Index greater than five. Results: Coexistence of OSA with epilepsy was found in 10.2% (15.4% of the male and 5.4% of the female) epilepsy patients investigated. The OSA was mild in 66.6%, moderate in 22.2%, and severe in 11.1% of the cases. The “epilepsy + OSA” patients were older, heavier, more frequently male, and sleepier (p < 0.05) than those with “epilepsy only.” Furthermore, they experienced their first seizure at an older age (p < 0.05). Conclusions: Systematic investigation reveals that OSA is frequent in epilepsy patients. The major risk factors for OSA in our epilepsy patients were the same as those typically found in the general population. Of the epilepsy-related factors, older age at onset of seizures appears to be significantly related to comorbidity with OSA (p < 0.05). The presence in epilepsy patients of these features should alert the clinician to the possibility of an underlying OSA. Key Words: Epilepsy—Obstructive sleep apnea.