Principles of antiepileptic drug action -- Neurophysiological effects of antiepileptic drugs -- Discovery and preclinical development of antiepileptic drugs -- New antiepileptic drug development: medical perspective -- Clinical development of antiepileptic drugs: industry perspective -- The development of antiepilepsy drugs: regulatory perspective -- Antiepileptic drug monotherapy in adults: selection and use in new-onset epilepsy -- Combination therapy and drug interactions -- Laboratory monitoring of antiepileptic drugs -- Safety monitoring of antiepileptic drugs -- Safety monitoring of antiepileptic drugs -- Use of antiepileptic drugs in children -- Antiepileptic drug use in women -- Epilepsy in the elderly -- Treatment of status epilepticus -- Prevention of epileptogenesis -- Sect.
Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Clinical efficacy and use in epilepsy -- Adverse effects -- Sect. Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Interactions with other drugs -- Clinical efficacy and use in epilepsy -- Clinical efficacy and use in other neurological disorders -- Clinical efficacy and use in psychiatric disorders -- Adverse effects Sect.
Felbamate -- Sect. Mechanisms of action -- Chemistry, biotransformation, pharmacokinetics, and interactions -- Clinical use -- Clinical efficacy and use in other neurological disorders -- Clinical efficacy and use in psychiatric disorders -- Adverse effects -- Sect.
Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Interactions with other drugs -- Clinical efficacy and use in epilepsy -- Efficacy and use in nonepileptic disorders -- Adverse effects -- Sect.
Mechanisms of action -- Chemistry, biotransformation, pharmacokinetics, and drug interactions -- Clinical use -- Adverse experiences -- Sect. Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Interactions with other drugs -- Clinical efficacy and use in epilepsy -- Clinical efficacy and use in psychiatric disorders -- Adverse effects -- Sect.
Phenobarbital and other barbiturates. Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Interactions with other drugs -- Clinical efficacy and use in epilepsy -- Clinical efficacy and use in nonepileptic disorders -- Adverse effects -- Methylphenobarbital -- Sect.
Phenytoin and other hydantoins. Mechanisms of action -- Chemistry and biotransformtion -- Interactions with other drugs-- Clinical efficacy and use in epilepsy -- Clinical efficacy and use in other neurological disorders -- Clinical efficacy and use in psychiatric disorders -- Adverse effects -- Fosphenytoin -- Sect. Primidone -- Sect. Mechanisms of action -- Ethosuximide: chemistry, biotransformation, pharmacokinetics, and drug interactions -- Clinical efficacy and use in epilepsy -- Adverse effects -- Methsuximide -- Sect.
Mechanisms of action -- Chemistry, biotransformation, and pharmacokinetics -- Drug interactions -- Clinical efficacy and use in epilepsy -- Clinical efficacy and use in nonepileptic disorders -- Adverse effects -- Sect. Valproic acid. ISBN x. Combinations of antiepileptic drugs frequently cause concern to prescribers. Interactions are known to occur, and in paediatrics the use of polytherapy indicates a failure of monotherapy to control seizures.
Polytherapy may occur when a second drug is introduced before the first is withdrawn, or as a long term measure in order to achieve seizure control. You will be able to get a quick price and instant permission to reuse the content in many different ways. Skip to main content. Log in via OpenAthens. Log in using your username and password For personal accounts OR managers of institutional accounts. Codes Patients were also required to have at least 1 claim with a diagnosis code of Patients meeting these diagnosis criteria may have had other epilepsy diagnoses during the study and were not excluded if other epilepsy codes were found.
Patients were assigned to an AED combination category based on their index combination. Treatment duration with the index AED combination was measured as the number of days from the index date to the end of the index combination, the end of enrollment, or the end of available data March 31, , whichever occurred first.
All-cause health care use was measured during the time of persistence with the index AED combination. For inpatient admissions, emergency department visits, and physician office visits, the proportion of patients using each resource and the mean number of services per patient were reported along with lengths of stay for inpatient admissions.
Clinical variables were measured for the 6 months prior to the index date. Comorbidity burden was evaluated using 3 indices: the Deyo-Charlson Comorbidity Index, the mean number of unique 3-digit International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, and the mean number of unique outpatient medications. Descriptive statistics for demographic and clinical variables were reported by AED combination category.
A critical value of 0. Multivariate logistic models were used to examine the relationship between the various health care use outcomes with AED combination categories. The proportionality assumption was tested for each predictor and no violation was detected. Analyses were conducted using Stata statistical software version The final study cohort consisted of patients who met all study criteria Figure 1. Mean SD age ranged from Cohorts receiving G combinations were generally older mean [SD] range, Combinations of G had higher percentages of female patients, with women comprising The latter cohort also had the highest mean SD number of unique outpatient medications pre-index Cohorts receiving different-MOA combinations had longer mean and median persistence compared with cohorts receiving same-MOA combinations Table 3.
The Cox proportional hazards models examining time to discontinuation showed different-MOA combinations with a lower hazard of discontinuation compared with same-MOA combinations Table 4.
Although findings with other SC or G combinations were not significant, the direction of these findings was consistent with lower hazards associated with different-MOA combinations. Logistic regression models examining the risk for inpatient admissions for G combinations found patients receiving different-MOA G combinations had a significantly lower risk for inpatient admission Table 6 , model 1; OR, 0.
Logistic regression models for SC combinations did not find statistically significant differences between SC combinations Table 6.
Logistic regression models examining the risk for an emergency department visit found no significant differences between G combination cohorts; however, point estimates were suggestive of lower risk for emergency department visits with combinations based on different MOAs Table 7. Logistic regression models of emergency department visits for patients with SC combinations found significantly lower risks for emergency department visits for different-MOA combinations Table 7 , model 1; OR, 0.
To our knowledge, based on our research and a review of the current literature, the current study is the first to describe AED combination therapy patterns by MOA in patients with POS in a real-world setting and to evaluate differences in outcomes comparing different-MOA combination therapy to same-MOA combination therapy. Many of the previous studies describing AED use were performed prior to the availability of the newer AEDs, did not reflect use in typical practice, and did not provide detail on specific AED combinations and outcomes resulting from their use.
Combinations containing an SC were prescribed for Of the patients receiving a combination containing G, only 8. The findings suggest that different-MOA—based combination AED therapies have been the most common in clinical practice whether or not by conscious awareness of the MOAs by the prescriber. These differences in chronic illnesses were particularly evident in the percentages of patients treated concomitantly with antidepressants, anxiolytics, antihypertensives, and statins.
All differences between SC and G combination cohorts for these comorbidities and concomitant medications were statistically significant. Prescribers of AEDs, or of any medication class, use comorbidity as one of the important factors in drug choice and therefore our results may also reflect that selection bias. Quiz Ref ID In this study, persistence with therapy was used as a proxy for effectiveness, having been an established proxy in both randomized clinical trials and prior epilepsy studies, assuming patients continued therapy owing to adequate seizure control and the absence of intolerable adverse events.
One possible explanation is the potential for noncompliance because of additive toxicity if the drugs in the combination exhibited similar adverse-effect profiles. Logistic regression of emergency department visits found significantly lower risks for emergency department visits for SC combinations of different MOAs, while G combinations showed no differences in the odds of an emergency department visit.
Logistic regression of inpatient admissions suggested a lower risk with different-MOA G combinations, while differences in hospitalization risk for SC combinations were not significant. As with treatment duration, other factors related to drug choices may impact outcomes. Additional research is needed to better understand the potential for the characteristics of a specific drug in a given MOA class to impact outcomes. Because this study could not establish causation, further research may more closely examine associations of comorbidities with AED selection and resulting outcomes.
Several study limitations should be noted. Drugs categorized in a particular MOA class may have different clinical, pharmacokinetic, and safety profiles that influence their use and so may limit the clinical implications of our findings. In view of other published works describing MOA-based combination therapy, the MOA categories selected for this study may not have been sufficiently detailed to detect differences between AED combinations.
The observed relationships could reflect the effects of unmeasured variables, such as severity of illnesses and seizure frequency, or incomplete capture of variables that determine the optimal AED combination for a given patient with POS.
Lastly, this study was limited to working-aged individuals or their dependents enrolled in commercial health care plans, so results may not be generalizable to other age groups or health care coverages. Quiz Ref ID These findings suggest that AED combinations with different MOAs have greater effectiveness, as measured by treatment persistence, and lower risks for hospitalization and emergency department visits, suggesting a strategy for achieving optimal AED combination therapy outcomes that is based on different MOAs rather than the same MOAs.
Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes in AED combination therapy and to identify additional factors that may influence outcomes when implementing an MOA-based combination therapy approach to POS management. Corresponding Author: Jay M.
Published Online: June 9, Author Contributions: Dr Margolis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Critical revision of the manuscript for important intellectual content: All authors. Drs Wang and Copher are employees of Eisai Inc. No other disclosures were reported. Role of the Sponsor: Eisai Inc had a role in the design and conduct of the study; analysis and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.
We acknowledge the key contributions of Larry Radbill, MA Truven Health Analytics , for his tireless work in defining, extracting, assembling, and analyzing the data. He did not receive funding from the study sponsor for his contributions. Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Download PDF Comment.
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