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Management of Acute Repetitive Seizures

Defining the Role of Rectal Diazepam Gel

  • Drugs in Disease Management
  • Published:
Disease Management and Health Outcomes

Abstract

Acute repetitive seizures, more commonly known as cluster, crescendo or sequential seizures, are defined as episodes of increased seizure activity occurring in patients with refractory epilepsy who are already receiving stable regimens of anticonvulsants. They lie in the seizure spectrum between isolated seizures and status epilepticus. If acute repetitive seizures are left untreated, they may progress to status epilepticus.

Acute repetitive seizures and prolonged seizures are rated as a neurological emergency and treatment must be prompt. The primary goals of therapy are cessation of the seizure and prevention of recurrence. The use of traditional intravenous agents such as phenytoin, phenobarbital (phenobarbitone), lorazepam and diazepam is well established in the first-line treatment of acute seizures. However, adverse effects and the time to onset of effect often dictate the choice between older anticonvulsants. Newer agents (such as fosphenytoin) and alternative routes of administration (such as rectal administration of diazepam solution) have been developed in an effort to reduce adverse effects, decrease the time to onset of effect, reduce acute care facility costs and investigate the possibility of home treatment.

Diazepam rectal gel, a newer formulation of diazepam intended for rectal administration, effectively terminates acute seizures and prevents recurrence within the first 12 hours after administration. Diazepam rectal gel is available for use by a trained caregiver in a home setting and, therefore, emergency room treatment and hospitalisation may not be required and could be avoided. This may result in reductions in financial and emotional costs associated with acute repetitive seizures, but broader clinical experience is needed to assess this. Diazepam rectal gel is not associated with respiratory depression and most adverse effects appear to be mild to moderate in severity.

At present, diazepam rectal gel is a valuable addition to the current anticonvulsant armamentarium for first-line therapy of acute repetitive seizures. Wider clinical experience will better determine the place of this formulation in the treatment of this debilitating disorder.

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Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Anna J. Matheson, Matthew N. Lowe, Katharine J. Palmer & Michelle I. Wilde

Authors
  1. Anna J. Matheson
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  2. Matthew N. Lowe
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  3. Katharine J. Palmer
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  4. Michelle I. Wilde
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Corresponding author

Correspondence to Anna J. Matheson.

Additional information

Various sections of the manuscript reviewed by: R. Kriel, Department of Neurology, Hennepin County Medical Center, Minneapolis, Minnesota, USA; I. Leppik, MINCEP Epilepsy Care, Minneapolis, Minnesota, USA; W. Mitchell, Neurology Department, Children’s Hospital, Los Angeles, California, USA; J. Pellock, Division of Child Neurology, Medical College of Virginia, Richmond, Virginia, USA; B.Uthman, Departments of Neurology and Neuroscience, University of Florida College of Medicine and Brain Institute, Gainsville, Florida, USA.

Data Selection

Sources: Medical literature published in any language since 1966 on Diazepam Rectal Gel, identified using Medline supplemented by AdisBase (a proprietary database of Adis International, Auckland, New Zealand). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘seizures’ or ‘epilepsy’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘repetitive seizures’ or ‘breakthrough seizures’ or ‘recurrent seizures’ or ‘acute repetitive seizures’ or ‘acute epileptic seizsure’ or ‘uncontrolled seizures’ or ‘Diazepam Rectal Gel’ and (‘review’ or ‘clinical-study’). Medline search terms were ‘epilepsy’ or ‘seizures’ and (‘guidelines’ or ‘decision-making’ or ‘health-policy’ or ‘managed-care-programmes’ or ‘epidemiology’ or ‘outcome-assessment-health-care’ or ‘clinical-protocols’ or ‘guideline in pt’ or ‘practice-guideline in pt’), or ‘Diazepam Rectal Gel’ and ‘review in pt’. Searches were last updated 13 Nov 2000.

Selection: Studies in patients with epilepsy who received diazepam rectal gel. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.

Index terms: epilepsy, diazepam, rectal, children, acute repetitive seizures, status epilepticus, pharmacoeconomics, disease management, review on treatment.

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Matheson, A.J., Lowe, M.N., Palmer, K.J. et al. Management of Acute Repetitive Seizures. Dis-Manage-Health-Outcomes 8, 355–368 (2000). https://doi.org/10.2165/00115677-200008060-00005

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