Status epilepticus - Emerging treatments

Intramuscular midazolam

One Cochrane review has shown that intramuscular administration of midazolam may be more effective than intravenous lorazepam at terminating seizures in people with status epilepticus in the pre-hospital setting, without any increase in recurrence of seizures or adverse events.[42] [ ]

Topiramate

Topiramate blocks voltage-gated sodium channels, enhances GABA transmission, blocks AMPA receptors of glutamate, and inhibits carbonic anhydrase. Reported effective in aborting SE in some patients when other medicines failed.[50][51]

Intranasal benzodiazepines

Diazepam nasal spray has been granted orphan drug status by the US Food and Drug Administration (FDA) for the treatment of acute repetitive seizures in all age groups. In a small retrospective study of stroke patients presenting with status epilepticus, intranasal diazepam compared favourably with the intravenous formulation.[52] Intranasal administration of diazepam may be a practical alternative to the conventional administration of acute medication in status epilepticus, especially in patients with no intravenous access. Intranasal midazolam is also in development.

Allopregnanolone analogues

Ganaxolone and brexanolone are a synthetic analogue of allopregnanolone, an endogenous neurosteroid that modulates the brain neurotransmitter GABA. In pre-clinical trials, intravenous ganaxolone yielded positive results in benzodiazepine-resistant status epilepticus.[53] The FDA has granted orphan drug designation to both drugs for the treatment of status epilepticus. While open-label phase II trials of ganaxolone and brexanolone have been promising, phase III trials have not met primary endpoints in refractory status epilepticus and super-refractory status epilepticus.[54][55]

Brivaracetam

Brivaracetam is an analogue of the anticonvulsant that displays high and selective affinity for synaptic vesicle glycoprotein 2A (SV2A) and is believed to reduce neuronal excitability by modulating synaptic transmission.[56] Oral brivaracetam has demonstrated efficacy for the adjunctive treatment of adults with focal seizures in randomised controlled clinical trials in the outpatient setting.[57][58][59][60] One retrospective observational study showed intravenous brivaracetam (n=56) to be effective in 32 (57%) of patients with status epilepticus.[61] Time to seizures resolution appears shorter when brivaracetam is administered in the early phases of status epilepticus.[61] Brivaracetam may be a valid alternative for the treatment of status epilepticus after the failure of first-line therapy.[62] However, it is not currently approved for this indication.