Brexanolone
Neuroactive steroid, GABA-A positive allosteric modulator
Brexanolone
Zulresso
Brexanolone (brand name Zulresso) is a cyclodextrin-based IV formulation of allopregnanolone, the body's own neuroactive steroid produced as a metabolite of progesterone. FDA-approved in March 2019 as the first medication specifically for postpartum depression (PPD). Administered as a single 60-hour continuous infusion in a REMS-certified inpatient setting due to risk of excessive sedation. The drug's rationale rests on the observation that allopregnanolone levels fall precipitously after delivery; rapidly restoring those levels via infusion produces a rapid antidepressant response that persists for 30+ days in trials.
Positive allosteric modulator at GABA-A receptors at a distinct neuroactive steroid binding site (separate from benzodiazepine and barbiturate sites). Modulates both synaptic (phasic, mostly benzo-sensitive α1/α2/α3/α5-containing) and extrasynaptic (tonic, mostly benzo-insensitive δ-containing) GABA-A receptors. The benzodiazepine-insensitive δ-containing extrasynaptic receptors are hypothesized to be the key target for antidepressant effect, since benzodiazepines themselves do not have antidepressant efficacy.
Experience
No personal reports yet
No clinical reports yet
Log in to add your own experience.
Problems
No problems yet. Be the first to suggest one.
+ Add a problemTitration strategies
No titration strategies yet. Be the first to suggest one.
Effects
Sedation (very common), loss of consciousness (REMS warning), syncope, dry mouth, flushing. Suicidal thoughts have been observed.
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
How much experience do you have with this combination (1 a little, 5 a lot)?
How did it go? (-100 worst, +100 best)
- checking this mechanism here
Relevant anecdote
No anecdotes yet. Share a relevant one.
Relevant Literature
No literature entries yet.
Log in to submit relevant literature.
Summary
Classes
Neuroactive steroid, GABA-A positive allosteric modulator
Common uses
Postpartum depression (PPD) in adults
Pharmacy
Starting dose
Single 60-hour continuous IV infusion: 30 mcg/kg/h × 4h → 60 mcg/kg/h × 20h → 90 mcg/kg/h × 28h → 60 mcg/kg/h × 4h → 30 mcg/kg/h × 4h
Preparations
100 mg/20 mL vial, single-use
US FDA Max
Single 60-hour course
Pharmacology
Routes
Intravenous (continuous infusion in a REMS-certified facility)
Onset
Antidepressant effect within hours of infusion start; sustained at 30 days
Duration
Single infusion course
Half-life
~9 hours (terminal)
Bioavailability
100% (IV)
Pregnancy
Drug is structurally identical to endogenous allopregnanolone; pregnancy considerations relate to breastfeeding during/after infusion. Limited data; brief interruption of breastfeeding considered
Legal status
Rx; REMS program required (excessive sedation/loss of consciousness during infusion)
Purported mechanism
Allopregnanolone (the body's own neurosteroid metabolite of progesterone) delivered IV. Positive allosteric modulator at both benzodiazepine-sensitive and benzodiazepine-insensitive GABA-A receptors. Hypothesized to act primarily at the benzodiazepine-insensitive site, which differentiates it from benzodiazepines (which lack antidepressant efficacy)