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A Common Reference-Based Indirect Comparison Meta-Analysis of Buccal versus Intranasal Midazolam for Early Status Epilepticus

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Abstract

Background

Intranasal and buccal midazolam have recently emerged as possible alternatives to intravenous or rectal diazepam or intravenous lorazepam in the treatment of early status epilepticus (SE). However, to date no randomized controlled trial (RCT) has directly compared intranasal midazolam with buccal midazolam.

Objective

The aim of this study was to indirectly compare intranasal midazolam with buccal midazolam in the treatment of early SE using common reference-based indirect comparison meta-analyses.

Methods

RCTs comparing intranasal or buccal midazolam versus either intravenous or rectal diazepam for early SE were systematically searched. Random-effects Mantel–Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy and safety of intranasal or buccal midazolam versus either intravenous or rectal diazepam. Adjusted indirect comparisons were then made between intranasal and buccal midazolam using the obtained results.

Results

Fifteen studies, with a total of 1662 seizures in 1331 patients (some studies included patients with more than one episode of SE) were included; 1303 patients were younger than 16 years. Indirect comparisons showed no difference between intranasal and buccal midazolam for seizure cessation (OR 0.98, 95 % CI 0.32–3.01, comparator: intravenous diazepam; OR 0.87, 95 % CI 0.46–1.64, comparator: rectal diazepam). For serious adverse effects, we found a large width and asymmetrical distribution of confidence intervals around the obtained OR of 2.81 (95 % CI 0.39–20.12; comparator: rectal diazepam). No data were available for OR using intravenous diazepam as the comparator.

Conclusions

Indirect comparisons suggest that intranasal and buccal midazolam share similar efficacy in the treatment of early SE in children. Intranasal midazolam should be used with caution and under clinical monitoring of vital functions. RCTs directly comparing intranasal midazolam with buccal midazolam are required to confirm these findings.

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Acknowledgments

We are indebted to Annalisa Cuzzoni (Medical Library of Bolzano) for developing and implementing the search strategies, and we thank Piero Bonzano and Vincenzo De Simone (Accord Healthcare), as well as Alberto Liuti (ViroPharma), for seeking information on unpublished randomized controlled trials on buccal midazolam or studies in progress.

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Authors and Affiliations

  1. Section of Clinical Neurology, Department of Neurological and Movement Sciences, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Francesco Brigo

  2. Department of Neurology, Franz Tappeiner Hospital, Merano, Italy

    Francesco Brigo, Raffaele Nardone & Frediano Tezzon

  3. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria

    Raffaele Nardone & Eugen Trinka

  4. Centre for Cognitive Neuroscience Salzburg, Salzburg, Austria

    Eugen Trinka

  5. Department of Public Health Technology Assessment, UMIT, University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria

    Eugen Trinka

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  1. Francesco Brigo
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  4. Eugen Trinka
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Corresponding author

Correspondence to Francesco Brigo.

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Funding

No funding was received in relation to the preparation of this article.

Conflicts of interest

Francesco Brigo has received speakers’ honoraria from UCB Pharma.

Eugen Trinka has acted as a paid consultant to Bial, Biogen Idec, Eisai, Ever Neuropharma, Medtronics, Takeda, Upsher-Smith, and UCB; has received speakers’ honoraria from Bial, Boehringer, Eisai, GL Lannacher, and UCB Pharma; and has received research funding from Biogen Idec, Merck, Novartis, Red Bull, UCB Pharma, the European Union, FWF (Österreichischer Fond zur Wissenschaftsförderung), and Bundesministerium für Wissenschaft und Forschung. Raffaele Nardone and Frediano Tezzon declare no conflicts of interest.

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Brigo, F., Nardone, R., Tezzon, F. et al. A Common Reference-Based Indirect Comparison Meta-Analysis of Buccal versus Intranasal Midazolam for Early Status Epilepticus. CNS Drugs 29, 741–757 (2015). https://doi.org/10.1007/s40263-015-0271-x

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  • DOI: https://doi.org/10.1007/s40263-015-0271-x

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