Pregabalin Reduces Seizures in Drug-Resistant Focal Epilepsy

By Will Boggs MD

July 31, 2019

NEW YORK (Reuters Health) - Pregabalin, when added to existing antiepileptic therapy, reduces seizure frequency in patients with drug-resistant focal epilepsy, according to a new Cochrane review.

Pregabalin is a newer antiepileptic drug used to improve outcomes, especially among the one-third of patients who continue to have seizures despite drug treatment.

Dr. Rebecca Bresnahan of the University of Liverpool, U.K., and colleagues, whose findings were published online July 9 in the Cochrane Database of Systematic Reviews, updated the 2014 review of pregabalin add-on for drug-resistant focal epilepsy. They included three new studies not covered in the earlier review.

In seven trials comparing pregabalin with placebo, patients randomized to pregabalin were 2.28-fold more likely to attain a 50% or greater reduction in seizure frequency, a significant difference. The odds of this response doubled with an increase in pregabalin dose from 300 mg/day to 600 mg/day.

The likelihood of seizure freedom was 3.94-fold greater with pregabalin than with placebo, also a significant result. But patients treated with pregabalin were 35% more likely to withdraw from studies for any reason and 2.65-fold more likely to withdraw for adverse effects, compared with placebo.

In three trials comparing pregabalin with active drugs, patients randomized to pregabalin were 47% more likely than those randomized to lamotrigine to achieve a 50% or greater reduction in seizure frequency, whereas this outcome was not significantly different for pregabalin versus levetiracetam or for pregabalin versus gabapentin.

Treatment withdrawal rates were similar for pregabalin and the other three active drugs.

Adverse events significantly associated with pregabalin included ataxia, dizziness, somnolence, weight gain and fatigue.

The authors rated the certainty of the evidence in these studies as very low to moderate.

Dr. Jacqueline French from NYU Comprehensive Epilepsy Center, New York, who has studied the use of adjunctive pregabalin for focal seizures but was not involved in this review, said, "The drug appeared more efficacious in trials than it has been in the clinic. It is in our armamentarium, but not first or second line."

"The risk of weight gain is problematic to patients," she told Reuters Health by email.

Dr. Bresnahan did not respond to a request for comments.


Cochrane Database Syst Rev 2019.