NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Cover of Effectiveness and Safety of Antiepileptic Medications in Patients With Epilepsy

Effectiveness and Safety of Antiepileptic Medications in Patients With Epilepsy

Comparative Effectiveness Reviews, No. 40

Investigators: , PharmD, , PharmD, , PharmD, , PharmD, , PharmD, , MD, MPH, , MD, FACC, , MS, , MS, , MS, , PharmD, and , PharmD, FCP, FCCP.

University of Connecticut/Hartford Hospital Evidence-based Practice Center
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 11(12)-EHC082-EF

Structured Abstract

Objectives:

This is an evidence report prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center examining the comparative efficacy, safety, and tolerability of newer versus older and innovator versus generic antiepileptic medications.

Data Sources:

MEDLINE (starting from 1950), Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews, and Web of Science from the earliest possible date through March 23, 2011.

Review Methods:

Controlled clinical trials and controlled observational studies were included in our comparative effectiveness review if they met the following inclusion criteria: compared older to newer antiepileptic medications or innovator to generic antiepileptic medications, conducted in patients with epilepsy, and reported data on prespecified clinical or humanistic outcomes. Using predefined criteria, data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes were extracted. All of the available data was qualitatively evaluated and where possible, statistically pooled. For dichotomous endpoints, we used relative risks, and for continuous endpoints, we used weighted mean differences or standardized mean differences. Both were calculated using a DerSimonian and Laird random effects model and reported with 95 percent confidence intervals. When mean change scores from baseline for each group were not reported, the difference between the mean baseline and mean followup scores for each group and the standard deviations of the change scores were calculated. I2 was used to detect statistical heterogeneity and Egger's weighted regression statistics were used to assess for publication bias. The strength of the body of evidence for each outcome was rated as insufficient, low, moderate, or high.

Results:

Patients given newer antiepileptic medications were less likely to be seizure free for 6–12 months or 24 months and had a greater risk of withdrawing due to a lack of efficacy than those receiving carbamazepine. The risk of withdrawing due to adverse events and the risk of several adverse events including fatigue, somnolence, dizziness, and skin rash were significantly reduced when patients received newer antieplipetic medications versus carbamezepine, but the risk of withdrawing for any reason was not significantly impacted. Similarly, patients receiving newer antiepileptic medications were more likely to withdraw due to a lack of efficacy than those receiving carbamazepine sustained or controlled release products but are more likely to withdraw due to adverse events and skin rash. The risk of withdrawing for any reason was not significantly impacted.

There was no significant difference in the risk of being seizure free for the study duration when newer antiepileptic medications were compared against phenytoin or valproic acid, or the risk of being seizure free at 6–12 or 24 months for valproic acid. No significant differences were seen for newer antiepileptic medications versus either phenytoin or valproic acid for withdrawals for any reason, withdrawals due to lack of efficacy, or withdrawals due to adverse events. The risk of certain adverse events including fatigue, somnolence, nausea, and alopecia were significantly lower for newer antiepileptic medications versus valproic acid. The risks of vomiting and gum hyperplasia were significantly lower for newer antiepileptic medications versus phenytoin. For the comparison of innovator antiepileptic medications to their respective generic versions, we found that seizure occurrence, seizure frequency, total withdrawals, withdrawals due to lack of efficacy, or withdrawals due to adverse events were not significantly different in controlled clinical trials. Using data from observational studies, switching from an innovator to a generic antiepileptic medication may increase the risk of hospitalization, hospital stay duration, and the composite of medical service utilization but may not increase outpatient service utilization.

Conclusions:

Carbamazepine had advantages in epilepsy control over newer antiepileptic medications as a class but had more adverse effects. Valproic acid and phenytoin provided epilepsy control similar to newer antiepileptic medications, but there were adverse events that occurred more commonly with these older antiepileptic medications. However, these adverse events did not significantly increase the risk of withdrawals.

In patients who need to initiate an antiepileptic medication, we could find no substantive differences in terms of benefits or harms associated with the use of an innovator versus a generic. There was insufficient to low strength of evidence suggesting that switching from an innovator to a generic, generic to generic, or generic to innovator version of the same medication may increase the short-term risk of hospitalization and hospital stay duration and may increase the short-term risk of a composite of having an emergency department and hospitalization visit with or without ambulance service utilization.

Contents

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10067-I. Prepared by: University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT

Suggested citation:

Talati R, Scholle JM, Phung OJ, Baker WL, Baker EL, Ashaye A, Kluger J, Quercia R, Mather J, Giovanale S, Coleman CI, White CM. Effectiveness and Safety of Antiepileptic Medications in Patients with Epilepsy. Comparative Effectiveness Review No. 40. (Prepared by the University of Connecticut/Hartford Hospital Evidence-based Practice Center under Contract No. 20-2007-10067-I.) AHRQ Publication No. 11(12)-EHC082-EF. Rockville, MD: Agency for Healthcare Research and Quality. December 2011. www.effectivehealthcare.ahrq.gov/reports/final.cfm

This report is based on research conducted by the University of Connecticut/Hartford Hospital Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10067-I). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

1

540 Gaither Road, Rockville, MD 20850; www‚Äč.ahrq.gov

Bookshelf ID: NBK83937PMID: 22359775

Views

Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...