Add-on gabapentin for refractory seizures in patients with brain tumours

Seizures associated with intracranial neoplasms are occasionally refractory to conventional anti-epileptic drugs. Gabapentin (GBP) is one of several novel anti-epileptic drugs effective as an add-on therapy for intractable seizures but has not been studied in patients with cerebral tumours.

We used GBP in a open-label add-on fashion to treat 14 patients with intractable seizures associated with intracranial tumours including four glioblastomas, four metastases, three recurrent glioblastomas, and one each of anaplastic and low grade astrocytoma and meningioma. GBP was added if optimization of pre-existing therapy failed and was titrated until seizures were controlled.

One patient experienced adverse drowsiness. Follow-up ranged from 3-24 weeks during which time 7 patients died from disease progression. Concurrent therapy included dexamethasone in eight, cranial irradiation in four, and radiosurgery in one. Responder rate (number with at least 50% fewer seizures) was 100% and persisted throughout follow-up. Complete resolution of seizures occurred in 8/14 patients.

GBP was well tolerated in patients with brain tumours. Seizure frequency was reduced in all patients and efficacy persisted over time; however, the mechanism of this improvement is unclear. Concurrent therapy, regression of frequency to the mean, and the lack of controls may account for apparent benefit. In addition, because GBP may interact with a leucine-related neuronal binding site we also speculate that this novel mechanism of action may have been enhanced in our patients due to the abnormal blood-brain barrier associated with cerebral tumours. Further investigation and a controlled trial are warranted.