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Background: Valproate (VPA) is a commonly prescribed antiepileptic drug for patients experiencing epileptic seizures due to brain tumors. VPA increases radiation sensitivity in various tumor cells in vitro due to complex mechanisms. This could make tumors more vulnerable to ionizing radiation or overcome radioresistance. Yet, clinical data on possible improvement of tumor control by adding VPA to tumor therapy is controversial. Potentially radiosensitizing effects of VPA on healthy tissue remain unclear. To determine individual radiosensitivity, we analyzed blood samples of individuals taking VPA., Methods: Ex vivo irradiated blood samples of 31 adult individuals with epilepsy were studied using 3-color fluorescence in situ hybridization. Aberrations in chromosomes 1, 2 and 4 were analyzed. Radiosensitivity was determined by the mean breaks per metaphase (B/M) and compared to age-matched (2:1) healthy donors., Results: The patient cohort (n = 31; female: 38.7%) showed an increase of their average B/M value compared to healthy individuals (n = 61; female: 56.9%; B/M: 0.480 ± 0.09 vs. 0.415 ± 0.07; p = .001). The portion of radiosensitive (B/M >  0.500) and distinctly radiosensitive individuals (B/M >  0.600) was increased in the VPA group (54.9% vs. 11.3 and 9.7% vs. 0.0%; p < .001). In 3/31 patients, radiosensitivity was determined prior to and after VPA treatment and radiosensitivity was increased by VPA-treatment., Conclusions: In our study, we confirmed that patients treated with VPA had an increased radiosensitivity compared to the control group. This could be considered in patients taking VPA prior to the beginning of radiotherapy to avoid toxic side effects of VPA-treatment.

Objective: Despite bioequivalence, the exchangeability of antiepileptic drugs in clinical settings is disputed. Therefore, we investigated the risk for recurrent seizures after switching the manufacturer of the same drug in a large German cohort., Methods: Anonymous patient data from practice neurologists throughout Germany between 2011 and 2016 were collected using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy were included if at least 2 prescriptions within 360 days and 1 within 180 days prior to the index date were available. The cohort was separated into a seizure group and seizure-free controls. Both groups were matched 1:1 according to age, gender, insurance status, and treating physician. The risk for breakthrough seizures after a manufacturer switch of the same antiepileptic drug was analyzed using multivariate regression models., Results: A total of 3,530 people with epilepsy were included (each group, n = 1,765; age = 53.7 ± 19.8 years). Patients with seizures had switched the drug manufacturer more often than controls (26.8% vs 14.2%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.08-1.69, p = 0.009), both from branded to generic (5.5% vs 2.4%; OR = 1.85, 95% CI = 1.30-2.64, p < 0.001) and between generic drugs (14.7% vs 7.1%; OR = 1.45, 95% CI = 1.13-1.87, p = 0.004)., Interpretation: In previously seizure-free patients, switching the manufacturer of antiepileptic medications was associated with a higher risk for seizure recurrence. Our retrospective approach does not allow us to determine whether other changes in medical care at the same time could contribute to the recurrence. However, it would be prudent to avoid switching the manufacturer of anticonvulsants in seizure-free patients. Ann Neurol 2018;84:918-925., (© 2018 American Neurological Association.)

Objective: Whether anti-seizure medication (ASM) increases the risk for cancer has been debated for decades. While for some ASM, a carcinoma-promoting effect has been suspected, carcinoma-protective effects have been shown for other ASM. However, the issue remains unresolved as data from preclinical and clinical studies have been inconsistent and contradictory. Methods: We collected anonymous patient data from practice neurologists throughout Germany between 2009 and 2018 using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy (PWE) with an initial cancer diagnosis and antiepileptic therapy prior to the index date were 1:1 matched with a control group of PWE without cancer according to age, gender, index year, Charlson Comorbidity Index, and treating physician. For both groups, the risk to develop cancer under treatment with different ASMs was analyzed using three different models (ever use vs. never use (I), effect per one (II) and per five therapy years (III). Results: A total of 3152 PWE were included (each group, n = 1,576; age = 67.3 ± 14.0 years). The risk to develop cancer was not significantly elevated for any ASM. Carbamazepine was associated with a decreased cancer risk (OR Model I: 0.699, p <.0001, OR Model II: 0.952, p =.4878, OR Model III: 0.758, p <.0004). Significance: Our findings suggest that ASM use does not increase the risk of cancer in epilepsy patients. [ABSTRACT FROM AUTHOR]