FDA approved Zulresso (brexanolone) injection for intravenous (IV) use for the treatment of postpartum depression (PPD) in adult women.
Brexanolone is positive allosteric modulator of γ-aminobutyric-acid type A (GABA A) receptors.
- continuous IV infusion over a total of 60 hours (2.5 days).
- Monitor for continuous pulse oximetry monitoring, excessive sedation and sudden loss of consciousness.
- Patients should not drive, operate machinery, or do other dangerous activities until feelings of sleepiness from the treatment have completely gone away.
Common Adverse Side Effects:
- dry mouth
- loss of consciousness
Zulresso REMS Program:
- Zulresso will be available only through a restricted program called the Zulresso REMS Program.
- This requires that Zulresso be administered by a health care provider in a certified health care facility.
- The REMS requires that patients be enrolled in the program prior to administration of the drug.
Clinical Study #1 (Lancet 2017)
Double-blind, randomised, placebo-controlled trial.
- Subject either must have ceased lactating at Screening; or if still lactating at Screening, must have already fully and permanently weaned their infant(s) from breastmilk; or if still actively breastfeeding at Screening, must agree to cease giving breastmilk to their infant(s) prior to receiving study drug.
- Subject has had a Major Depressive Episode that began no earlier than the third trimester and no later than the first 4 weeks following delivery, as diagnosed by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I).
- Subject is ≤ 6 months postpartum.
- Subject must be amenable to IV therapy.
- Active psychosis
- Attempted suicide associated with index case of postpartum depression
- Medical history of seizures
- Medical history of bipolar disorder
- Eligible women were randomly assigned (1:1) to receive either a single, continuous intravenous dose of brexanolone or placebo for 60 hours.
- At 60 h, mean reduction in HAM-D total score from baseline was 21·0 points (SE 2·9) in the brexanolone group compared with 8·8 points (SE 2·8) in the placebo group (difference −12·2, 95% CI −20·77 to −3·67; p=0·0075; effect size 1·2).
- No deaths, serious adverse events, or discontinuations because of adverse events were reported in either group.
- Four of ten patients in the brexanolone group had adverse events compared with eight of 11 in the placebo group.
- The most frequently reported adverse events in the brexanolone group were dizziness (two patients in the brexanolone group vs three patients in the placebo group) and somnolence (two vs none).
- Moderate treatment-emergent adverse events were reported in two patients in the brexanolone group (sinus tachycardia, n=1; somnolence, n=1) and in two patients in the placebo group (infusion site pain, n=1; tension headache, n=1); one patient in the placebo group had a severe treatment-emergent adverse event (insomnia).
Clinical Study #2 (Lancet 2018)
double-blind, randomised, placebo-controlled, phase 3 trials
Patients were randomly assigned (1:1:1) to receive a single intravenous injection of either:
- Brexanolone 90 μg/kg per h (BRX90)
- Brexanolone 60 μg/kg per h (BRX60), or
- Matching placebo for 60 h in study 1, or (1:1) BRX90 or matching placebo for 60 h in study 2.
- In study 1, at 60 h, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19·5 points (SE 1·2) in the BRX60 group and 17·7 points (1·2) in the BRX90 group compared with 14·0 points (1·1) in the placebo group (difference −5·5 [95% CI −8·8 to −2·2], p=0·0013 for the BRX60 group; −3·7 [95% CI −6·9 to −0·5], p=0·0252 for the BRX90 group).
- In study 2, at 60 h, the LS mean reduction in HAM-D total score from baseline was 14·6 points (SE 0·8) in the BRX90 group compared with 12·1 points (SE 0·8) for the placebo group (difference −2·5 [95% CI −4·5 to −0·5], p=0·0160). In study 1, 19 patients in the BRX60 group and 22 patients in the BRX90 group had adverse events compared with 22 patients in the placebo group.
- In study 2, 25 patients in the BRX90 group had adverse events compared with 24 patients in the placebo group.
- The most common treatment-emergent adverse events in the brexanolone groups were headache (n=7 BRX60 group and n=6 BRX90 group vs n=7 placebo group for study 1; n=9 BRX90 group vs n=6 placebo group for study 2), dizziness (n=6 BRX60 group and n=6 BRX90 group vs n=1 placebo group for study 1; n=5 BRX90 group vs n=4 placebo group for study 2), and somnolence (n=7 BRX60 group and n=2 BRX90 group vs n=3 placebo group for study 1; n=4 BRX90 group vs n=2 placebo group for study 2).
- In study 1, one patient in the BRX60 group had two serious adverse events (suicidal ideation and intentional overdose attempt during follow-up).
- In study 2, one patient in the BRX90 group had two serious adverse events (altered state of consciousness and syncope), which were considered to be treatment related.
- FDA News Release (FDA)
- Lancet. 2017 Jul 29;390(10093):480-489. (pubmed)
- Lancet. 2018 Sep 22;392(10152):1058-1070. (pubmed)
Post by: Dr. Harvinder Singh, M.D. (Admin & Course Instructor)
Enroll in our online course to have access to similar clinically relevant psychiatry topics.