Article Text

Download PDFPDF

Buccal midazolam may be a useful alternative to rectal diazepam for treating acute seizures in refractory epilepsy
  1. Samuel Wiebe, MD, MSc
  1. University of Western Ontario London, Ontario, Canada

    Statistics from

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

 QUESTION: In children and adolescents with refractory epilepsy, is buccal midazolam in solution as effective and safe as rectal diazepam in solution for treating acute seizures?


    Randomised (allocation concealed*), unblinded,* controlled trial with follow-up to end of seizure.


    A residential centre for children and young people with severe epilepsy and other needs in Lingfield, Surrey, UK.


    18 of 42 enrolled students with refractory epilepsy (mean age 15 y, 50% girls) who had previously received rectal diazepam for acute seizures and who had a seizure that lasted ≥3 minutes during the study period. Follow-up was complete.


    When a seizure occurred, the student was allocated to receive either midazolam, 2 ml (10 mg) in a 2 ml syringe given buccally (n=40 seizures in 14 patients), or diazepam, 10 mg given rectally (n=39 seizures in 14 patients).

    Main outcome measures

    Clinical response (seizure stopped within 10 min), time taken for nurse to give medication, time to clinical response, and incidence of adverse events.

    Main results

    In the midazolam group, 24 seizures were generalised tonic-clonic, 8 were complex partial, 6 were myoclonic, and 2 were tonic. In the diazepam group, 22 seizures were tonic-clonic, 9 were complex partial, 4 were myoclonic, and 4 were tonic. The treatment groups did not differ for clinical response (p=0.16) (table), time required for nurse to give medication (median time 2 min in each group, p=0.81), time to clinical response (median time 6 min for midazolam v 8 min for diazepam, p=0.31), and incidence of adverse events (none occurred in either group). When patients rather than seizures were the units of analysis, the groups did not differ for any of the outcomes.

    Buccal midazolam v rectal diazepam for acute seizures in children and adolescents with refractory epilepsy†


    In children and adolescents with refractory epilepsy, buccal midazolam was as effective and safe as rectal diazepam for treating acute seizures.


    Although rectal diazepam is effective in prolonged acute seizures,1 it has practical problems. Scott and colleagues' promising evidence of the effectiveness of buccal midazolam is welcome. However, clinicians should consider some issues before adopting it.

    Study patients had severe epilepsy and had received diazepam. Would patients receiving a benzodiazepine for the first time respond similarly? A nurse gave midazolam, and medical care was available. Neither of these is normally present in the community. Efficacy, safety, and the optimal doses for young children and elderly people remain to be determined. Finally, patients with prolonged seizures, not status epilepticus, were treated.

    The study methods deserve comment. Seizures (not patients) were randomised, and 50% of seizures occurred in 2 of 18 patients. Data from more patients would reassure clinicians. Blinding would have required concurrent buccal and rectal administration. I believe, however, that it is feasible in this context, and it would have strengthened the findings.

    Buccal midazolam offers definitive advantages over rectal diazepam and may be used as an alternative for young people with prolonged, complex partial, and generalised motor seizures. However, its safety and efficacy in the community require further exploration.


    View Abstract


    • Source of funding: no external funding.

    • For correspondence: Dr R C Scott, Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK. FAX +44-(0)171-833-9469.

    • * See glossary.