Verapamil: No Benefit as AED Adjuvant in Reducing Seizure Frequency

Verapamil adjuvant therapy showed no benefit versus placebo in patients with refractory epilepsy on standard antiepileptic drug (AED) treatment

VANCOUVER, BC—Verapamil adjuvant therapy showed no benefit vs. placebo in patients with refractory epilepsy on standard antiepileptic drug (AED) treatment, a study presented at the 68th AAN Annual Meeting has found.

Verapamil, a calcium-channel blocker, has been reported as a potential AED adjunctive therapy for patients with refractory epilepsies, such as those in status epilepticus and with severe myoclonic epilepsy of infancy and focal onset seizures; specifically, temporal lobe epilepsy (TLE). However, to date, no controlled clinical trials have been conducted to support its efficacy.

The investigators hypothesized that verapamil would decrease AED efflux from epileptic brain tissue, reducing seizure frequency.

To evaluate the safety and efficacy of verapamil, Felippe Borlot, MD, of the Division of Neurology and Epilepsy Genetics Program at Toronto Western Hospital /University Health Network, University of Toronto, Toronto, Ontario, Canada, and colleagues conducted a randomized trial in three phases: an 8-week baseline phase, a 16-week double-blind treatment phase, and a 12-week open-label treatment extension phase.

In the double-blind phase, 22 patients were randomly assigned to take verapamil 80mg or placebo once daily for 1 week, then twice daily during the second week, then 80mg three times daily from the third week onwards. In the open-label extension phase, all patients received 240mg verapamil daily.

A total of 12 patients finished the study, and “none of the patients studied reached 50% reduction in seizure frequency,” the results showed.

“The average seizure frequency of the patients in the verapamil group did not significantly change from baseline in either the double-blind (P=0.86) or open-label (P=0.80) study phase,” Dr. Borlot noted. “The average seizure frequency of patients in the verapamil group against those in the placebo at both the double-blind and open-label study phases also failed to pass significance (P=0.41 and P=0.98, respectively).”

“The best response we had was in a 20-year-old patient with frontal lobe epilepsy due to cortical dysplasia,” who had a seizure reduction of 41.3%, the investigators reported. “Even then, the response was not sustained through the open-label phase.” 

Throughout the study, AED levels were tested. Following verapamil treatment, levels of both carbamazepine and clobazam increased, and a minor dosage adjustment was required in 1 patient on carbamazepine.

Patients in both the verapamil and placebo groups reported side effects from the study that included drowsiness, feeling faint, fatigue, nausea, and weight gain, leading to study withdrawals. Adverse events unique to verapamil were skin rashes and foot edema.

“Verapamil seems to be helpful for patients with SCN1A mutations or with focal onset seizures due to TLE,” they concluded. “Further placebo-controlled studies on those groups would help, clarifying the role of verapamil as an add-on therapy in human epilepsies.”