Skip to main content
Journal cover image

Brexanolone as adjunctive therapy in super-refractory status epilepticus.

Publication ,  Journal Article
Rosenthal, ES; Claassen, J; Wainwright, MS; Husain, AM; Vaitkevicius, H; Raines, S; Hoffmann, E; Colquhoun, H; Doherty, JJ; Kanes, SJ
Published in: Ann Neurol
September 2017

OBJECTIVE: Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning. METHODS: Patients receiving TLAs for SRSE control were eligible for open-label, 1-hour brexanolone loading infusions, followed by maintenance infusion. After 48 hours of brexanolone infusion, TLAs were weaned during brexanolone maintenance. After 4 days, the brexanolone dose was tapered. Safety and functional status were assessed over 3 weeks of follow-up. RESULTS: Twenty-five patients received open-label study drug. No serious adverse events (SAEs) were attributable to study drug, as determined by the Safety Review Committee. Sixteen patients (64%) experienced ≥1 SAE. Six patient deaths occurred, all deemed related to underlying medical conditions. Twenty-two patients underwent ≥1 TLA wean attempt. Seventeen (77%) met the response endpoint of weaning successfully off TLAs before tapering brexanolone. Sixteen (73%) were successfully weaned off TLAs within 5 days of initiating brexanolone infusion without anesthetic agent reinstatement in the following 24 hours. INTERPRETATION: In an open-label cohort of limited size, brexanolone demonstrated tolerability among SRSE patients of heterogeneous etiologies and was associated with a high rate of successful TLA weaning. The results suggest the possible development of brexanolone as an adjunctive therapy for SRSE requiring pharmacological coma for seizure control. Ann Neurol 2017;82:342-352.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

September 2017

Volume

82

Issue

3

Start / End Page

342 / 352

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Status Epilepticus
  • Retrospective Studies
  • Recurrence
  • Pregnanolone
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rosenthal, E. S., Claassen, J., Wainwright, M. S., Husain, A. M., Vaitkevicius, H., Raines, S., … Kanes, S. J. (2017). Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol, 82(3), 342–352. https://doi.org/10.1002/ana.25008
Rosenthal, Eric S., Jan Claassen, Mark S. Wainwright, Aatif M. Husain, Henrikas Vaitkevicius, Shane Raines, Ethan Hoffmann, Helen Colquhoun, James J. Doherty, and Stephen J. Kanes. “Brexanolone as adjunctive therapy in super-refractory status epilepticus.Ann Neurol 82, no. 3 (September 2017): 342–52. https://doi.org/10.1002/ana.25008.
Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, et al. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017 Sep;82(3):342–52.
Rosenthal, Eric S., et al. “Brexanolone as adjunctive therapy in super-refractory status epilepticus.Ann Neurol, vol. 82, no. 3, Sept. 2017, pp. 342–52. Pubmed, doi:10.1002/ana.25008.
Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, Hoffmann E, Colquhoun H, Doherty JJ, Kanes SJ. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017 Sep;82(3):342–352.
Journal cover image

Published In

Ann Neurol

DOI

EISSN

1531-8249

Publication Date

September 2017

Volume

82

Issue

3

Start / End Page

342 / 352

Location

United States

Related Subject Headings

  • Young Adult
  • Treatment Outcome
  • Status Epilepticus
  • Retrospective Studies
  • Recurrence
  • Pregnanolone
  • Neurology & Neurosurgery
  • Middle Aged
  • Male
  • Humans