Excerpted by the National Guideline Clearinghouse (NGC)
Each clinical recommendation is rated based on the strength of the evidence. Definitions of the strength of the recommendations (standard, guideline, practice option) and quality of the evidence (Class I-Class III) are presented at the end of the Major Recommendations field.
Summary
Twelve studies have examined, either in randomized controlled trials or cohort studies, the ability of prophylactic anticonvulsants to prevent first seizures in patients with brain tumors, and none have demonstrated efficacy. Four of these studies provide level I evidence. A meta-analysis of these four studies also revealed no evidence of an effect on the frequency of first seizures in patients receiving anticonvulsant prophylaxis. In contrast, deleterious interactions with cytotoxic drugs and corticosteroids are a major concern, and the incidence and severity of anticonvulsant side effects appear to be appreciably higher (20 to 40%) in brain tumor patients than in the general population of patients receiving anticonvulsants. This increased incidence is due at least in part to the additive or synergistic effects of concurrently administered drugs (especially chemotherapeutic agents) and to the underlying brain tumor.
Conclusions
Seizures are a common and sometimes devastating complication of brain tumors, and meticulous attention to their diagnosis and treatment is critical. The available evidence suggests, however, that prophylactic administration of anticonvulsant medications does not provide substantial benefit (i.e., a risk reduction of 26% or more for seizure-free survival), whereas anticonvulsant-associated side effects are especially common and occasionally life-threatening.
Many patients who experienced seizures while receiving anticonvulsant prophylaxis had subtherapeutic anticonvulsant blood levels. Although this may provide one explanation for the ineffectiveness of anticonvulsant prophylaxis in some patients, it did not change the conclusions of the one randomized controlled trial that addressed that issue specifically. In that study, 23% of patients receiving anticonvulsant prophylaxis who experienced a seizure had subtherapeutic levels. Reanalysis excluding patients with subtherapeutic levels still showed no benefit for anticonvulsant prophylaxis. Moreover, even in the setting of scrupulously monitored prospective studies in epileptic patients, subtherapeutic levels are extremely common, partly because of drug interactions. Rather than change the implications of these studies, this high rate of subtherapeutic levels simply reflects a clinical reality.
Clinical Recommendations
- In patients with newly diagnosed brain tumors, anticonvulsant medications are not effective in preventing first seizures. Because of their lack of efficacy and their potential side effects, prophylactic anticonvulsants should not be used routinely in patients with newly diagnosed brain tumors (Standard).
- In patients with brain tumors who have not had a seizure, tapering and discontinuing anticonvulsants after the first postoperative week is appropriate, particularly in those patients who are medically stable and who are experiencing anticonvulsant-related side effects (Guideline).
Definitions:
Strength of the Recommendations:
Standard. A principle for patient management that reflects a high degree of clinical certainty (usually requires one or more Class I studies that directly address the clinical question, or overwhelming Class II evidence when circumstances preclude randomized clinical trials).
Guideline. A recommendation for patient management that reflects moderate clinical certainty (usually requires one or more Class II studies or a strong consensus of Class III evidence).
Practice Option. Strategy for patient management for which clinical utility is uncertain (inconclusive or conflicting evidence or opinion).
Quality of the Evidence:
Class I. Must have all of a through d. (a) Prospective study of a well-defined cohort which includes a description of the nature of the population, the inclusion/exclusion criteria, demographic characteristics such as age and sex, and seizure type. (b) The sample size must be adequate with enough statistical power to justify a conclusion or for identification of subgroups for whom testing does or does not yield significant information. (c) The interpretation of evaluations performed must be done blinded to outcome. (d) There must be a satisfactory description of the technology used for evaluations (e.g., electroencephalogram, magnetic resonance imaging).
Class II. Must have a or b. (a) Retrospective study of a well-defined cohort which otherwise meets criteria for class 1a, b and 1d. (b) Prospective or retrospective study which lacks any of the following: adequate sample size, adequate methodology, a description of inclusion/exclusion criteria, and information such as age, sex and characteristics of the seizure.
Class III. Must have a or b. (a) A small cohort or case report. (b) Relevant expert opinion, consensus, or survey. A cost-benefit analysis or a meta-analysis may be class I, II, or III, depending on the strength of the data upon which the analysis is based.
