Top research findings of 2018-2019 for clinical practice

Conclusion

• These findings of moderate reductions in heavy drinking days and drinks per week with prazosin suggest that prazosin may be a promising harm-reduction treatment for alcohol use disorder.

4. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070.

Postpartum depression is among the most common complications of childbirth. It can result in considerable suffering for mothers, children, and families. Gamma-aminobutyric acid (GABA) signaling has previously been reported to be involved in the pathophysiology of postpartum depression. Meltzer-Brody et al⁵ conducted 2 double-blind, randomized, placebo-controlled, phase 3 trials comparing brexanolone with placebo in women with postpartum depression at 30 clinical research centers and specialized psychiatric units in the United States.

Study design

• Participants were women age 18 to 45, Palatino LT Std≤6 months postpartum at screening, with postpartum depression as indicated by a qualifying 17-item Hamilton Depression Rating Scale (HAM-D) score of ≥26 for Study 1 or 20 to 25 for Study 2.
• Of the 375 women who were screened simultaneously across both studies, 138 were randomly assigned (1:1:1) to receive a single IV injection of brexanolone, 90 μg/kg per hour (BRX90) (n = 45), brexanolone, 60 μg/kg per hour (BRX60) (n = 47), or placebo (n = 46) for 60 hours in Study 1, and 108 were randomly assigned (1:1) to receive BRX90 (n = 54) or placebo (n = 54) for 60 hours in Study 2.
• The primary efficacy endpoint was change in total score on the HAM-D from baseline to 60 hours. Patients were followed until Day 30. 

Outcomes

• In Study 1, at 60 hours, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19.5 points (standard error [SE] 1.2) in the BRX60 group and 17.7 points (SE 1.2) in the BRX90 group, compared with 14.0 points (SE 1.1) in the placebo group.
• In Study 2, at 60 hours, 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.
• In Study 1, one patient in the BRX60 group had 2 serious adverse events (suicidal ideation and intentional overdose attempt during follow-up). In Study 2, one patient in the BRX90 group had 2 serious adverse events (altered state of consciousness and syncope), which were considered treatment-related.

Conclusion

• Administration of brexanolone injection for postpartum depression resulted in significant, clinically meaningful reductions in HAM-D total score at 60 hours compared with placebo, with a rapid onset of action and durable treatment response during the study period. These results suggest that brexanolone injection has the potential to improve treatment options for women with this disorder.

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