New rapid acting medication for post partum depression

Depression in the post-partum stage is seen in 10-20% of all mothers. It is a leading cause of maternal mortality and has long standing negative consequences on the child. Changes in plasma allopregnanolone ,especially the abrupt decrease post-partum, is linked to the precipitation of depression 2.  Plasma allopregnanolone is a neuro active steroid with potent positive modulatory effect on extra synaptic GABA receptors. Rapid metabolism and poor bioavailability prevent the use of the oral form of allopregnanolone. Brexanolone , an intravenous  formulation of allopregnanolone, is showing promise in the treatment of post-partum depression.3

Kanes et al., carried out a randomised double blind, parallel group placebo controlled study across four sites in USA.3 Twenty-one women with severe depression ,within the initial 6 months period post-partum, participated in this study. A single continuous IV infusion of Brexanolone was administered for 60 hours . Outcome Assessments were done on day 30. At the end of 60 hours, the HAMD total score decreased by 21 points in brexanolone group compared with 8.8 points in placebo group. This was more or less maintained up to day 30 (the study end point). At 60 hours, seven out of ten patients receiving brexanolone met remission criteria compared with one in placebo arm.  On day 30, seven patients reached remission on active treatment compared to two with placebo. The medication was well tolerated. Overall side effects were higher in the placebo arm. Tachycardia, sedation, and dizziness were reported with brexanolone.

This study provides the first robust evidence of the effectiveness of brexanolone, an extra synaptic GABAa receptor modulator, in treating post-partum depression. The rapid onset of action is particularly useful given the serious impact (e.g., disrupted bonding)  of the illness on mother and baby . This is a promising start and if replicated is likely to find its way into clinical practice, given the key role played by post-partum depression in maternal mortality.

References

  1. Balon R. Has psychopharmacology entered a blind alley? Ann Clin Psychiatry Off J Am Acad Clin Psychiatr. 2017 Aug;29(3):157–8.
  2. Nappi RE, Petraglia F, Luisi S, Polatti F, Farina C, Genazzani AR. Serum allopregnanolone in women with postpartum “blues.” Obstet Gynecol. 2001 Jan;97(1):77–80.
  3. Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet Lond Engl. 2017 Jun 12; doi: 10.1016/S0140-6736(17)31264-3.

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