Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors [RETIRED]: Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract

The Quality Standards Subcommittee seeks to develop scientifically sound, clinically relevant practice parameters for the practice of neurology.Practice parameters are strategies for patient management that assist physicians in clinical decision making.A practice parameter is one or more specific recommendations based on analysis of evidence on a specific clinical problem.These might include diagnosis, symptoms, treatment, or procedure evaluation.American Academy of Neurology (AAN) members have requested the publication of a practice parameter on the use of prophylactic anticonvulsants in patients with primary and metastatic brain tumors.Justification.Physicians often administer anticonvulsant medication prophylactically to patients with brain tumors, despite the lack of definitive evidence that prophylactic anticonvulsant therapy is effective in preventing first seizures.[1][2][3][4] If anticonvulsant medications were free of side effects, their prophylactic use might be attractive even without such evidence.However, discomfort, expense, and inconvenience result from drug treatment and periodic monitoring of serum drug concentrations.Typical anticonvulsant-induced side effects, including cognitive impairment, myelosuppression, liver dysfunction, and dermatologic reactions (ranging from minor rashes to life-threatening Stevens-Johnson syndrome), appear to occur more frequently in patients with brain tumors than in other patient groups, 3,[5][6][7][8][9][10][11][12][13][14][15][16] although direct comparison studies have not been published.A spectrum of side effects unique to patients with brain tumors must also be considered.Phenytoin, carbamazepine, and phenobarbital reduce the efficacy of corticosteroids, [17][18][19][20][21] which are administered almost universally to brain tumor patients.In addition, the ability of these anticonvulsants to stimulate the cytochrome P450 enzyme system results in markedly accelerated metabolism of a wide spectrum of chemotherapeutic agents including nitrosoureas, paclitaxel, cyclophosphamide, topotecan, irinotecan, thiotepa, 9-aminocampo-thecin, adriamycin, and methotrexate. [22][23]3][24][25][26][27][28][29][30][31][32][33][34] As a result, inadequate chemotherapeutic dosing of brain tumor patients has been identified recently as a widespread and critically important problem.35 Conversely, corticosteroids and many chemotherapeutic agents alter the metabolism of anticonvulsants, making anticonvulsant under-and overdosing more common.[35][36][37][38][39][40][41][42][43][44][45] The potential immunosuppressive effect of anticonvulsant medications represents an additional risk to this already immunocompromised patient population. [46][47]][48][49] In 1998, more than 170,000 patients were diagnosed with brain metastases, and more than 34,000 developed primary brain tumors.[50][51][52] Twenty to 40% of all brain tumor patients have experienced a seizure by the time their brain tumor is diagnosed.3,4,11,12,[14][15][16][53][54][55][56][57][58][59][60][61] In these patients, the need for anticonvulsant medication is clear.Patients who have not experienced a seizure remain at risk, however, and at least 20 to 45% more (depending on factors such as tumor histology, location, age, and treatment) will ultimately develop seizures.3,4,[11][12][13][14][15][16][57][58][59][60][61] Because the number of newly diagnosed brain tumor patients is increasing yearly, [62][63][64][65] the question of whether to administer prophylactic anticonvulsants is being posed to neurologists with increasing frequency by their patients and by colleagues in neurosurgery, internal medicine, oncology, and radiation oncology.Although a number of studies have attempted to answer this question, 3,[11][12][13][14][56][57][58][59][60][66][67][68] these studies have used differing epidemiologic techniques, patient populations, treatment regimens, and outcome measures, and there remains no consensus among physicians about the optimum approach to this problem. Currently,he decision to administer From the American Academy of Neurology, St.