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Brexanolone (Allopregnanolone) (Brand Name Zulresso) has Been Approved for the Treatment of Postpartum Depression

By Aly W. | First published March 25, 2019 | Last modified October 5, 2020

This is only indirectly related to transfeminine hormone therapy, but it’s interesting and is somewhat relevant so I thought I’d post it.

Essentially, an intravenous formulation of allopregnanolone, known as brexanolone when used as a medication (brand name Zulresso), has been developed and approved for the treatment of postpartum depression in women. It appears to be very effective for this purpose. This is particularly interesting considering that this medication is one of the first non-monoaminergic antidepressants to be introduced into medicine (others include esketamine and tianeptine).

Allopregnanolone is of course notable in that it’s an endogenous neurosteroid and major active metabolite of progesterone, especially of oral progesterone. (Allopregnanolone and pregnanolone are responsible for the central depressant side effects of oral progesterone like sedation, anxiolysis, euphoria, cognitive/memory impairment, loss of motor coordination/balance, sleep improvement, and so forth.) It should be made clear though that it’s unlikely that oral progesterone would provide the antidepressant benefits of brexanolone. This is because 1) no antidepressant effects of oral progesterone have been reported in clinical studies as far as I’m aware; 2) the effectiveness of oral progesterone for treating premenstrual syndrome is inconclusive despite decades of studies (suggesting inadequate efficacy) (Wiki); and, perhaps most importantly, 3) the doses of brexanolone/Zulresso used and consequent levels of allopregnanolone achieved are very high—notably resulting in loss of consciousness as a possible side effect. Also, we don’t know if the antidepressant effects of brexanolone generalize outside of postpartum depression.

See here for a graph of the results of the phase 3 randomized controlled trials of brexanolone for postpartum depression. The mean change in score on the Hamilton Depression Rating Scale (HAM-D) was –12.8 for placebo and –17.0 for brexanolone at 60 hours of therapy and was –14.3 for placebo and –16.9 for brexanolone at 30 days of therapy. Hence placebo had 75% of the benefit of brexanolone at 60 hours and 84% of the benefit of brexanolone at 30 days. This degree of effectiveness relative to placebo is fairly typical for antidepressants (Aly W., 2020).

Aside from brexanolone, oral versions such as ganaxolone (AdisInsight) and zuranolone (AdisInsight) are being developed as well.