The use of prophylactic anticonvulsants in patients with brain tumours—a systematic review

QUESTIONS: Should patients with newly diagnosed brain tumours receive prophylactic anticonvulsants to reduce seizure risk? What is the best practice for patients with brain tumours who are taking anticonvulsant medications but who have never had a seizure? PERSPECTIVES: Patients with primary or metastatic brain tumours who have never had a seizure still have a 20% risk of experiencing a seizure over the course of their disease. Because considerable practice variation exists in regard to the management of patients with brain tumours who have never had a seizure, and because conflicting evidence has been reported, the Neuro-oncology Disease Site Group (dsg) of Cancer Care Ontario’s Program in Evidence-based Care felt that a systematic review of the evidence was warranted. OUTCOMES: Outcomes of interest were incidence of seizures and adverse effects of prophylactic anticonvulsant therapy. METHODOLOGY: The medline and Cochrane Library databases were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (rcts), systematic reviews, meta-analyses, and practice guidelines. The present systematic review was reviewed and approved by the Neuro-oncology dsg, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. RESULTS: QUALITY OF EVIDENCE: The literature search located one evidence-based practice guideline, one systematic review, and five rcts that addressed prophylactic anticonvulsants for patients with brain tumours. Evidence for the best management of seizure-naïve patients who are already taking anticonvulsants was limited to one retrospective study and exploratory analyses within several rcts. BENEFITS AND HARMS: Pooled results of the five rcts suggest that the incidence of seizures in patients who receive prophylactic anticonvulsants is not significantly different from that in patients who do not receive anticonvulsants (relative risk: 1.04; 95% confidence interval: 0.70 to 1.54; p = 0.84). This analysis accords with results from a published meta-analysis. Evidence is insufficient to determine whether patients who are currently taking anticonvulsants but who have never had a seizure should taper the anticonvulsants. Patients who received anticonvulsants reported adverse effects, including rash, nausea, and hypotension, but whether these effects are a result of the anticonvulsants or of other treatments could not be determined. CONCLUSIONS: Based on the available evidence, the routine use of postoperative anticonvulsants is not recommended in seizure-naïve patients with newly diagnosed primary or secondary brain tumours, especially in light of a significant risk of serious adverse effects and problematic drug interactions. Because data are insufficient to recommend whether anticonvulsants should be tapered in patients who are already taking anticonvulsants but who have never had a seizure, treatment must be individualized.