Anak Agung Ngurah Bagus Nugraha, Anak Agung Mas Wiryati

Efficacy of diazepam nasal spray in pediatric seizures: a systematic review

Introduction

Efficacy of diazepam nasal spray in pediatric seizures: a systematic review. Systematic review: Diazepam nasal spray shows high efficacy (84-90% control) and good safety for pediatric seizures, making it a promising first-line rescue therapy.

Abstract

Background: Acute seizures are a neurological emergency in children that require rapid intervention to prevent complications. Benzodiazepines are the first-line therapy; however, intravenous access is often difficult in pediatric patients, while rectal diazepam is associated with social and practical limitations. Diazepam nasal spray has been developed as a practical alternative with rapid absorption through the nasal mucosa. Nevertheless, evidence in the pediatric population remains limited and has not yet been systematically reviewed. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Literature searches were performed in Pubmed, ScienceDirect, and Google Scholar (2015-2025) using keywords related to diazepam nasal, seizure, and pediatric. Eligible studies included clinical trials, observational studies, or post hoc analyses evaluating the efficacy and/or safety of diazepam nasal spray in patients aged 0–18 years. Extracted data included study design, sample size, primary outcomes (time to seizure termination ≤10 minutes, need for a second dose within 24 hours), and secondary outcomes (seizure-free duration, recurrence, need for rescue therapy, and adverse events). Results: Five studies (total pediatric population ≈ 600) were included. Diazepam nasal spray demonstrated high efficacy, with 84–90% of seizure episodes controlled by a single dose; the mean need for a second dose was 12% (range 9.3–16.3%). Pharmacokinetics studies reported peak plasma concentration (Cmax) ranging from 94–280 ng/ml with a median Tmax of 3–5 hours, consistent with dosing at 0.2–0.3 mg/kg. Adverse events were generally mild and related to the nasal route of administration, including rhinorrhea (10-25%), nasopharyngitis (12–22%), pyrexia (10–22%), and somnolence (6–10%). No serious respiratory depression was reported in pediatric patients. Conclusion: Diazepam nasal spray appears to be a promising first-line rescue therapy for pediatric seizure clusters, offering rapid onset, high efficacy, good safety profile, and better social acceptability compared to the rectal route. However, current evidence is of low to very low quality (GRADE: low–very low) due to the predominance of open-label designs, industry sponsorship, and limited pediatric-specific data. Independent randomized controlled trials are still required to confirm efficacy and safety in pediatric population.

Review

This systematic review addresses a critical need in pediatric emergency neurology by evaluating the efficacy of diazepam nasal spray for acute seizures, offering a practical alternative to often challenging intravenous access or socially restricted rectal administration. The authors followed PRISMA guidelines, searching major databases for clinical trials and observational studies in patients aged 0-18 years. The findings from five included studies involving approximately 600 pediatric patients are promising, demonstrating high efficacy with 84–90% of seizure episodes controlled by a single dose and a mean 12% need for a second dose. The review also highlighted a favorable safety profile, with adverse events being predominantly mild and local to the nasal route, and crucially, no serious respiratory depression reported. Overall, the review concludes that diazepam nasal spray is a promising first-line rescue therapy with rapid onset, high efficacy, good safety, and improved social acceptability. Despite the positive findings, the review transparently acknowledges significant limitations regarding the quality of the current evidence. The authors critically assigned a GRADE of low to very low quality due to the prevalence of open-label designs, industry sponsorship, and a scarcity of pediatric-specific data in the existing literature. Further methodological scrutiny reveals potential areas for improvement in the review itself. The search strategy, while utilizing key databases, lacks specificity in terms of detailed search strings or MeSH terms, which are standard for comprehensive systematic reviews and crucial for reproducibility. The inclusion of Google Scholar as a primary database, while potentially casting a wider net, may also introduce studies of varying quality. Furthermore, the small number of included studies (five) underscores the nascent stage of research in this area and explains the authors' cautious conclusion regarding the overall evidence quality. Nonetheless, this systematic review serves as a valuable preliminary synthesis of the existing literature, laying a foundation for future research and clinical considerations. The potential for a rapidly administered, non-invasive, and socially acceptable rescue therapy for pediatric seizures is immense, offering significant benefits for caregivers and emergency responders. The review appropriately concludes with a strong call for independent, randomized controlled trials to definitively confirm the efficacy and safety of diazepam nasal spray in the pediatric population. Future research should aim to address the identified quality gaps, perhaps including head-to-head comparisons with other rescue medications like buccal midazolam, and explore efficacy across specific age groups or seizure types to further refine clinical guidelines. This review effectively highlights the current state of evidence and provides clear direction for advancing the field.

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