ORIGINAL RESEARCH article
Front. Neurol.
Sec. Pediatric Neurology
Safety and Effectiveness of Diazepam Nasal Spray in Patients with Rett Syndrome and Seizure Clusters: Post Hoc Analyses from a Long-Term Safety Study and Survey of Severity and Burden
Daniel Tarquinio 1
James Wheless 2,3
Eric B Segal 4,5
Adrian L. Rabinowicz 6,7
Enrique Carrazana 8,9
1. Center for Rare Neurological Diseases LLC, Norcross, United States
2. Le Bonheur Children's Hospital, Memphis, United States
3. The University of Tennessee Health Science Center, Memphis, United States
4. Hackensack Meridian Hackensack University Medical Center, Hackensack, United States
5. Northeast Regional Epilepsy Group, New York, United States
6. Neurelis, Inc, San Diego, United States
7. Florida Atlantic University Charles E Schmidt College of Medicine, Boca Raton, United States
8. University of Hawai'i at Manoa John A Burns School of Medicine, Honolulu, United States
9. Neurelis Inc, San Diego, United States
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Abstract
Introduction: Rett syndrome is a neurodevelopmental disorder associated with epilepsy that influences motor/communication skills, behavior, and other systems. Clinical experiences for these patients are not well described. Methods: This post hoc analysis consists of a patient subgroup with Rett syndrome enrolled in an open-label, single-arm, safety study. Age-and weight-based doses of diazepam nasal spray (5–20 mg) were administered to patients (aged 6-65 years) for seizure clusters. Treatment-emergent adverse events (TEAEs) were recorded, and days between seizure clusters (SEIzure interVAL [SEIVAL]) from Period 1 (P1; days 1–90) to Period 4 (P4; days 271–360) were calculated. Caregivers completed surveys describing experiences with diazepam nasal spray and Rett syndrome. Results: Rates of TEAEs (87.5%), serious TEAEs (12.5%), and treatment-related TEAEs (18.8%) in patients with Rett syndrome (n=16) who received diazepam nasal spray were comparable to the overall pediatric safety population (87.2%, 35.9%, and 14.1%, respectively; n=78), as was use of second doses (proxy for effectiveness) (18.4% and 11.4%). Increase in SEIVAL was also similar (P1=7.6, P4=25.0 days and P1=13.0, P4=25.9 days). Most (n=12; 75.0%) remained in the study ≥12 months. All caregivers felt diazepam nasal spray was very/extremely easy to use; 63.6% were able to return to normal activities within an hour of administration. Caregiver perceptions of clinical severity and caregiver affect were stable from baseline to final visits; scores for individuals using diazepam nasal spray were numerically higher. Conclusion: Diazepam nasal spray has safety and effectiveness profiles consistent with the full study population and was easy to use.
Summary
Keywords
caregiver, developmental epileptic encephalopathy, Natural variability, questionnaire, Rescue therapy, SEIVAL, Seizure clusters
Received
09 September 2025
Accepted
29 January 2026
Copyright
© 2026 Tarquinio, Wheless, Segal, Rabinowicz and Carrazana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Daniel Tarquinio
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