Abstracts

The overexpression of P-glycoprotein (P-gp) in the central nervous system may be one mechanism of pharmacoresistance in patients with epilepsy. Based on this, it would seem beneficial to block P-gp[acute]s ability to remove AEDs from the epileptic focus in pharmacoresistant patients. One known P-gp inhibitor is verapamil, a calcium-channel blocker. Verapamil may function to block P-gp modulated efflux of AEDs in the brain, thereby raising the intracellular concentration of AEDs and ultimately decreasing seizure burden. We describe 3 patients with pharmacoresistant seizures in whom we used adjunctive verapamil therapy for its P-gp inhibitory effects. Two women and one man were identified as having pharmacoresistant seizures as evidenced by their current seizure burden while on AED polytherapy and previous inadequacy or toxicity of every possible AED, vagus nerve stimulators and epilepsy surgery. One 25 YO woman had static encephalopathy, while the other woman (24 YO) and man (35 YO) were otherwise healthy. Verapamil sustained-release (Calan SR) 180 mg PO QD was added to each of their existing AED regimens. Due to concerns with potential hypotension caused by verapamil in these normotensive patients, they were given home blood pressure monitors. They were closely monitored for efficacy and toxicity via telephone and clinic visits. If the intervention was viewed as beneficial, the verapamil dose was titrated upward. All three patients showed improvement in seizure control and subjective quality of life. The verapamil dosages ranged from 180 to 480 mg/day. The 24 YO female patient showed the most significant improvement. The average time interval between her hospitalizations for complex partial status pre-verapamil was 55.1 [plusmn] 14.9 days. This interval more than doubled to 120.5 [plusmn] 21.9 days after the addition of verapamil. No side effects from verapamil were noted in any patient, and blood pressure readings and pulse were within the expected ranges. Two patients required a change in therapy (AED and VNS) while we were prospectively evaluating the adjunctive verapamil. The 35 YO male had to have his carbamazepine (CBZ) dose decreased due to symptomatic toxicity from adding the verapamil. Though the postulated mechanism is that verapamil is inhibiting the P-gp pump, other possible mechanisms include the metabolic inhibition of CBZ metabolism, the potential inherent anti-epileptic activity of verapamil, the [uml]placebo response[uml], and/or a combination of these factors. We are cautiously optimistic about the option of using verapamil as adjunctive therapy in pharmacoresistant patients. We advocate for further detailed studies. We suggest that the careful use and monitoring of adjunctive verapamil may offer hope for reduced seizure burden and improved quality of life in patients with pharmacoresistant seizures.