Epilepsy treatment in adults and adolescents: Expert opinion, 2016

Shih, Jerry J.; Whitlock, Julia B.; Chimato, Nicole; Vargas, Emily; Karceski, Steven; Frank, Ryan D.

doi:10.1016/j.yebeh.2016.11.018

Cited by 89 publications

(87 citation statements)

References 59 publications

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“…On the other hand, one cannot state that all CBZ should be switched to another non‐EI AED; for example, if the patient has achieved seizure‐freedom but is subsequently found to have side effects on important metabolic pathways, there is nonetheless a real risk of seizure recurrence if he/she should be switched to some other AED. All of these challenges might be avoided by assigning the appropriate drug in the first place with respect to the latest expert opinion on treatment of epilepsy, which compared to earlier surveys, highlights a move away from CBZ as the drug of choice …”

Section: Discussionmentioning

confidence: 99%

“…All of these challenges might be avoided by assigning the appropriate drug in the first place with respect to the latest expert opinion on treatment of epilepsy, which compared to earlier surveys, highlights a move away from CBZ as the drug of choice. 33 received speaker honoraria from Cyberonics, Eisai, Medtronic, Orion Pharma, and UCB; received support for travel congresses from Cyberonics, Eisai, Medtronic, and UCB; and participated in advisory boards for Cyberonics, Eisai, Medtronic, UCB, and Pfizer.…”

Section: Discussionmentioning

confidence: 99%

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Discontinuation of carbamazepine due to concerns of long‐term consequences of enzyme induction

et al. 2018

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SummaryObjectiveTreatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure‐free patients. We aimed to address this issue using a controlled observational study design.MethodsFifty‐eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long‐term adverse‐effects; 34 discontinued its therapy and 24 continued with CBZ. Six‐month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, sex hormone–binding globulin (SHBG), free testosterone, and 25‐hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients.ResultsSeizure‐free patients had a 5‐fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51–49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected.SignificanceDiscontinuation of CBZ in seizure‐free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Discontinuation of carbamazepine due to concerns of long‐term consequences of enzyme induction

et al. 2018

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“…Phenytoin is used for the treatment of focal onset and generalized tonic‐clonic seizures and status epilepticus, and for prevention of seizures following traumatic brain injury or neurosurgery. Although newer generation antiseizure drugs are recommended as the drugs of choice for chronic seizure disorders, phenytoin is still widely used . It exerts its effects by inhibiting voltage‐gated sodium channels, prolonging the inactivation phase and stabilizing the cell from hyperexcitability .…”

Section: Predictive Equations For Estimating Free Phenytoin Concentramentioning

confidence: 99%

Predicting Unbound Phenytoin Concentrations: Effects of Albumin Concentration and Kidney Dysfunction

et al. 2019

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Study Objective Several methods are available to predict unbound (free) phenytoin concentrations in patients with hypoalbuminemia; however, predictive methods have not been evaluated in patients with concurrent hypoalbuminemia and kidney dysfunction or in patients with mild to moderate (estimated glomerular filtration rate [eGFR] 30‐90 ml/min/1.73 m2) kidney dysfunction alone. Thus the objective was to evaluate the accuracy and precision of predictive methods to estimate free phenytoin concentrations in patients with varying albumin concentrations and/or kidney dysfunction. Design Retrospective chart review. Setting Large academic medical center. Patients A total of 344 patients with free and total phenytoin, albumin, and serum creatinine concentrations obtained between November 2012 and May 2017. Measurements and Main Results Free phenytoin concentrations were estimated in patients without kidney dysfunction using the Winter‐Tozer, Anderson, Kane, and Cheng equations. For the analysis in patients with eGFR lower than 90 ml/min/1.73 m2, free phenytoin concentrations were estimated using the Shiner‐Tozer derivation with adjusted affinity coefficients (C = 0.15, 0.20, 0.25, and 0.30). For both analyses, accuracy of predictive methods was evaluated by P20, the proportion of estimations within 20% of the measured free phenytoin concentration. In 158 patients with normal kidney function/normal albumin concentrations, 73 with normal kidney function/hypoalbuminemia, or 47 with mild kidney dysfunction/normal albumin concentrations, the Anderson method had the highest accuracy (86%, 82%, and 92%, respectively) and highest precision compared with the other methods. In 47 patients with normal albumin concentrations and mild kidney dysfunction or 13 with moderate kidney dysfunction, the free fraction was unchanged, and total phenytoin concentrations accurately reflected free concentrations. In 17 patients with hypoalbuminemia and mild or 17 with moderate kidney dysfunction, the Winter‐Tozer (67% and 50%, respectively) and the Anderson (56% and 67%, respectively) methods had the highest accuracy compared with other methods with significantly lower accuracy compared with patients with normal kidney function. In the 14 patients with severe kidney dysfunction and hypoalbuminemia, none of the coefficients had a P20 accuracy greater than 45%. Conclusion In patients with normal albumin concentrations, with or without mild or moderate kidney dysfunction and not receiving a protein‐binding displacer, the free fraction of phenytoin is unchanged, and it is not necessary to measure a free phenytoin concentration. Free phenytoin concentrations should be measured directly in patients with hypoalbuminemia and kidney dysfunction.

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“…(Chong & Lerman, 2016) In the U.S., more than twenty anti-seizure medications and two implantable devices are available for the treatment of epilepsy. (Shih et al, 2017) However, the treatment options depend on the types of epilepsy and individual traits. (Chong & Lerman, 2016) This large number of treatment options can introduce decision-making challenges for clinicians.…”

Section: Introductionmentioning

confidence: 99%

“…(Chong & Lerman, 2016) This large number of treatment options can introduce decision-making challenges for clinicians. (Shih et al, 2017) Moreover, debate regarding the comparative safety and effectiveness of AEDs in the real world causes additional clinical difficulties. (Wahab, 2010)…”

Section: Introductionmentioning

confidence: 99%

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

et al. 2017

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Objective Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Methods Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. Results A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5,077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. Significance Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study.

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Epilepsy treatment in adults and adolescents: Expert opinion, 2016

Cited by 89 publications

References 59 publications

Discontinuation of carbamazepine due to concerns of long‐term consequences of enzyme induction

Discontinuation of carbamazepine due to concerns of long‐term consequences of enzyme induction

Predicting Unbound Phenytoin Concentrations: Effects of Albumin Concentration and Kidney Dysfunction

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

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