Initial clinical evidence on biperiden as antiepileptogenic after traumatic brain injury. A Randomized Clinical Trial

Abstract

There is currently no available drug to prevent the development of post-traumatic epilepsy. Preclinical studies support the potential use of anticholinergics. To evaluate whether treatment with biperiden has the potential to prevent post-traumatic epilepsy. Randomized, double-blind, placebo-controlled clinical trial, conducted between 2018- 2022. Adult patients with acute traumatic brain injury (TBI) following eligibility criteria were randomly assigned to placebo or biperiden groups. Biperiden or placebo was initiated within 12 h after trauma and repeated every 6 h for 10 days. Clinical evaluation was performed at 1, 3, 6, 12, 18, and 24 months after TBI to investigate seizures incidence. The primary outcome was a change in the incidence of post-traumatic epilepsy. Secondary outcomes included frequency of seizures, mortality and adverse events. Of 123 patients recruited, 1 declined and 1 was ineligible. After randomization, 11 (8.9%) participants were discontinued from the study. The mean (SD) age of the 112 remaining participants was 43.5 (17.6) years, and 19/112 (16.9%) were female. Of these, 27 (21.9%) participants died and 3 (2.4%) were lost in the follow-up. Of the remaining 82 (66.6%) participants, 61 (49.5%) completed the study. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65-10.57; P = .170) or the mortality rate (1.57, 95%CI, 0.73-3.38; P=.248). Constipation (43.9%) was the most common adverse event observed. The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912-3.1597; p <0.001). There was insufficient evidence regarding the effect of biperiden in preventing post-traumatic epilepsy after TBI. The combined effect of variables known to have an impact on the likelihood of developing late post-traumatic seizures and its unbalanced frequency in the different groups is an aspect to be considered and underpins the need for larger studies.