Overcoming barriers to the management of seizure clusters: ease of use and time to administration of rescue medications

Figures & data

Table 1. Advantages and disadvantages of FDA-approved rescue medications.

Route	Drug(s)	Advantages	Disadvantages
Rectal	Diazepam	Can administer relatively large dose volume Relatively painless Patient cooperation not needed [11]	Inconsistent absorption and bioavailability, which could potentially influence treatment response Preparation for administration could delay treatment, prolonging seizure duration [24] Invasive [16] Limited medications can be delivered by this route Poor social acceptability Potential for leakage [11] Difficulty with positioning the patient for proper administration [34]
Intranasal	Diazepam Midazolam	Quick and easy administration, potentially expediting time to seizure cessation Noninvasive [16] Relatively fast absorption and onset of action Patient cooperation not needed Relatively painless Avoids first-pass metabolism Socially acceptable vs rectal route Possible direct-to-brain delivery of drug	Need for delivery device (eg, atomizer) Possible CNS AEs Variable absorption and bioavailability depending on mucosal health and specific benzodiazepine Formulations require high drug concentration in a small volume Nasal/throat discomfort, inflammation, lacrimation, abnormal taste Need to enhance drug solubility

Note: Abbreviations: AEs, adverse events; CNS, central nervous system; FDA, US Food and Drug Administration.

Adapted from Cloyd et al, 2021 [8] with permission from John Wiley and Sons

Figure 1. Ease of Use of Diazepam Nasal Spray and Diazepam Rectal Gel. a: Ease of administering diazepam nasal spray for caregivers and self-administering patients. b: Caregiver ease/comfort with administration of diazepam rectal gel compared with diazepam nasal spray.

Figure 2. Time to Diazepam Nasal Spray Administration. Time to administration expressed as cumulative percentiles of patients (eg, 25th, 50th, 75th), from onset of the seizure cluster to treatment for all patients (a: n = 162; 3627 seizures) and self-administrators (b: n = 26; 814 seizures). For example, 75% of all patients (a) received diazepam nasal spray in ≤5 minutes from seizure-cluster onset.

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