Low Rate of Cognitive and Psychiatric Side Effects Seen With Cenobamate Treatment of Seizures in Clinical Trials
Post hoc analysis was conducted to further examine low rates of cognitive and psychiatric side effects of cenobamate (Xcopri; SK Life Sciences, Paramus, NJ) observed in clinical trials. Cenobamate is approved for adjunctive treatment of partial-onset seizures in adults.
Analysis of pooled data showed, at baseline, participants in clinical trials had memory impairment (2.2% to 6.5% of patients), depression (10.6% to 14.3% of patients), and anxiety (6.6% to 11.1% of patients). During double-blind studies, reports of these as adverse events among people treated with cenobamate 100 to 400 mg/day, however, were low—ranging from less than 2% for cognitive side effects (eg, word-finding difficulties, memory impairment, mathematical challenges) and less than 3% for psychiatric side effects (eg, confusion, anxiety, irritability, depression, suicidal ideation, and mood swings). Word-finding difficulty occurred slightly more often (3.6%) with 400 mg/day cenobamate and anxiety was higher (3.2%) in individuals treated with placebo.
Exposure-adjusted event-rate analysis over 1 to 5 years of data suggest that cognitive and psychiatric side effects of cenobamate can be expected in only 1 to 2 of every 100 patients treated. The incidence of psychiatric and cognitive side effects was also lower when cenobamate was titrated more slowly.
In the open-label study of cenobamate, participants were allowed to discontinue concomitant medications, and this may also have contributed to the lower rate of psychiatric and cognitive problems seen with cenobamate treatment. Additionally, cenobamate treatment provided high rates of seizure freedom (~36% of those treated had at least 1 year of seizure freedom), which might also positively contribute to lower psychiatric comorbidity.
William E. Rosenfeld, MD, epileptologist/neurologist and principal investigator at the Comprehensive Epilepsy Care Center for Children and Adults in St. Louis, Missouri commented, “I would encourage clinicians to consider cenobamate as a first adjunctive treatment because onset of efficacy occurs quickly—despite the need for titration, psychiatric and cognitive side effects are low, a high proportion of people treated achieve impressive seizure reduction, and many are able to lower use of concomitant antiseizure medications.
In clinical trials, median reduction in focal-to-bilateral tonic-clonic seizures was 94% from baseline in the first 1 to 3 month of treatment, and seizure reduction occurred as early as the first 2 to 4 weeks of treatment. More than 50% of participants treated in a large phase 3 trial had 75% or more seizure reduction (3-month intervals) at a little over 2 years of treatment. High rates of seizure freedom (3-month intervals) after 24 or more months of treatment have also been seen for focal aware motor seizures (48% of participants) and focal impaired awareness (54% of participants) with cenobamate treatment.
The data on psychiatric and cognitive side effects of cenobamate were presented at the American Academy of Neurology Annual Meeting 2022 held in Seattle, WA April 2-7.