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This publication is provided for historical reference only and the information may be out of date.

Cover of Management of Treatment-Resistant Epilepsy

Management of Treatment-Resistant Epilepsy

Evidence Reports/Technology Assessments, No. 77

Investigators: , PhD, , PhD, , PhD, , PhD, , PhD, and , PhD.

Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 03-0028ISBN-10: 1-58763-081-8

Structured Abstract


This report, commissioned at the request of the Centers for Disease Control and Prevention and the Social Security Administration, addresses in an evidence-based fashion diagnosis of and interventions for treatment-resistant epilepsy (TRE). It addresses drug and surgical treatments, as well as service-related interventions.

Search Strategy:

We systematically searched 23 electronic databases, including PubMed® and EMBASE. Search dates ranged from 1985 to January 1, 2002 for all but drug topics, which ranged from 1975 to January 1, 2002. We employed different search strategies for each of the nine key questions addressed. Our searches identified 11,111 articles.

Selection Criteria:

We retrieved 2,356 articles, and included 357, according to a priori criteria accounting for the quality and relevance of available studies.

Data Collection and Analysis:

We employed a “best evidence” synthesis that used the best available, not the best possible evidence. Case control studies were the most common design for diagnostic topics, RCTs were most common for antiepileptic drug (AED) strategies, and the surgical literature was nearly all retrospective case series. The quality of these studies was systematically considered. We computed summary statistics in meta-analyses of RCTs of multiple AED therapy (polytherapy) and computed thresholds for effectiveness in meta-analyses of sequential AED monotherapy and uncontrolled surgical studies.

Main results:

There is no widely used definition of TRE. Lack of high quality studies precludes an evidence-based determination of the most effective diagnostic for rediagnosing or re-evaluating patients. Nevertheless, up to 35 percent of patients (but probably fewer) diagnosed with TRE may also have nonepileptic seizures, or not have epilepsy at all. Not all patients diagnosed with TRE receive optimized therapy, but the number of these patients cannot be determined. Initiation of sequential monotherapy appears to result in seizure increases in many patients, and whether sequential monotherapy causes any patients to become seizure-free is not clear. Polytherapy can reduce seizure frequency, but some patients experience intolerable adverse effects. Drug reduction may cause seizure increases without additional benefit. Results of the AED studies assessed in this report may not be generalizable to drugs not examined in the studies we included. Temporal lobe surgery eliminates seizures in many patients. Hemispherectomy and frontal lobe surgery eliminate seizures in an indeterminate number of patients. Corpus callosotomy reduces seizure frequency but generally does not eliminate seizures. Vagal nerve stimulation affords some seizure reduction. There was insufficient evidence to assess other treatments. Epilepsy is associated with increased all-cause mortality and death from drowning. The link between sudden death and seizure frequency is uncertain. Generalized tonic-clonic seizures seem associated with an increased risk of death.


Some patients diagnosed with treatment-resistant epilepsy are misdiagnosed or not receiving optimized AED treatment. Effective treatments are available, but all have disadvantages. There are many weaknesses in the current literature, particularly in studies of diagnostics and nondrug, nonsurgical interventions. Better-designed studies in these areas are needed.


Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.1 Contract No. 290-97-0020. Prepared by: ECRI Evidence-based Practice Center, Plymouth Meeting, PA.

Suggested citation:

Chapell R, Reston J, Snyder D. Management of Treatment-Resistant Epilepsy. Evidence Report/Technology Assessment No. 77. (Prepared by the ECRI Evidence-based Practice Center under Contract No 290-97-0020.) AHRQ Publication No. 03-0028. Rockville, MD: Agency for Healthcare Research and Quality. May 2003.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or 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.

AHRQ is the lead Federal agency charged with supporting research designed to improve the quality of health care, reduce its cost, address patient safety and medical errors, and broaden access to essential services. AHRQ sponsors and conducts research that provides evidence-based information on health care outcomes; quality; and cost, use, and access. The information helps health care decisionmakers—patients and clinicians, health system leaders, and policymakers—make more informed decisions and improve the quality of health care services.

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

Bookshelf ID: NBK36968


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