EpilepsiaIntranasal Midazolam vs. Mouth-Dissolving Clobazam in Terminating Seizures: A Randomized Controlled Trial

⚠️ Small Study / Early Comparative Evidence

Investigators compared mouth-dissolving clobazam with intranasal midazolam for terminating prolonged seizures in an epilepsy monitoring unit. The prospective, randomized, open-label, blinded-endpoint trial enrolled 95 patients with drug-resistant epilepsy who were already receiving clobazam as part of polytherapy. Participants received either rescue treatment when a seizure lasted longer than two minutes. Time to clinical and electrographic seizure termination did not differ significantly between groups. Although the authors proposed clobazam as a potentially convenient and cost-effective alternative, the study did not use an equivalence or noninferiority design and does not establish interchangeable efficacy.

Clinical Considerations

• The trial randomized 47 patients to intranasal midazolam and 48 to mouth-dissolving clobazam.
• Time to clinical seizure termination did not differ significantly between treatment groups by log-rank analysis (P=.17).
• Time to electrographic termination also showed no statistically significant between-group difference (P=.39).
• The clinical-termination hazard ratio was 0.39 (95% CI, 0.15-1.02; P=.05), with the confidence interval reflecting substantial uncertainty.
• Neither arm had reported significant adverse effects, treatment failure, or seizure recurrence, and treatment satisfaction did not differ significantly.
• The single-center study involved a small, selected population receiving chronic clobazam treatment, which may limit generalizability to other patients and out-of-hospital settings.

Practice Applications

• Interpret the absence of a statistically significant difference as inconclusive rather than evidence of equivalence between the rescue treatments.
• Recognize that treatment inside an epilepsy monitoring unit does not directly validate effectiveness or feasibility in prehospital use.
• Review established seizure action plans and approved rescue therapies when selecting treatment for prolonged or clustered seizures.
• Consider mouth-dissolving clobazam an investigational rescue strategy requiring larger, appropriately designed comparative trials.
• Monitor subsequent studies addressing dosing, treatment timing, caregiver administration, respiratory safety, recurrence, and real-world outcomes.