Clobazam in Adult Drug-Resistant Epilepsy: Excellent Long-Term Retention and Potential Synergy with Neuromodulation

INTRODUCTION: Drug-resistant epilepsy (DRE) is a major clinical challenge. While clobazam, a 1,5-benzodiazepine, is an effective adjunctive therapy, concerns regarding tolerability and discontinuation rates have been reported in some studies. This study evaluates the long-term efficacy and tolerability specifically among adults with DRE who successfully tolerated at least six months of clobazam treatment at a Level 4 Epilepsy Center, providing insights into outcomes in treatment-tolerant patients. METHODOLOGY: A single-center retrospective chart review was conducted of 160 adult patients with DRE treated with clobazam for at least six months at a Level 4 Epilepsy Center. Data on seizure frequency, clobazam dosage, tolerability, and concomitant therapies, including neuromodulation devices, were analyzed. RESULTS: = 160; 80, 50%, female; mean age 37.4 years) achieved significant seizure reduction at a mean clobazam dosage of 20 mg/day. Notably, 62 (38.8%) of patients achieved seizure freedom or near-freedom (≤1 seizure per year). Among patients who tolerated clobazam for at least six months, long-term retention was excellent, with only 5% subsequently discontinuing due to adverse effects. In patients with a vagus nerve stimulator (VNS) or responsive neurostimulation (RNS) device (67, 42% of the cohort), concomitant clobazam therapy resulted in additional reductions in seizure frequency. CONCLUSIONS: Among adults with DRE who successfully tolerate at least six months of clobazam therapy, long-term retention is excellent (95%), and sustained efficacy is maintained. These findings provide valuable insight into long-term outcomes, specifically in treatment-tolerant patients. Furthermore, combination therapy with neuromodulation demonstrates potential complementarity. These findings provide valuable insight into long-term outcomes in treatment-tolerant patients and suggest that careful ongoing management optimizes clinical outcomes in adult DRE.