Zuranolone Improved Depression, Anxiety and Insomnia in Postpartum Depression

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Zuranolone is a neurosteroid developed in the treatment of postpartum depression.

Neurosteroids or Neuroactive Steroids (NAS) are endogenous steroid hormones synthesised from cholesterol in the mitochondria of glial cells or from steroid hormone precursors like progesterone that accumulate in the nervous system that act locally and rapidly to affect brain function and behaviour.

Neurosteroids have been reported to act on many neuronal receptors, including GABA-A, sigma1, glutamate, glycine, serotonin, and acetylcholine receptors.

Neurosteroids in Psychiatry – Pharmacology | Mechanisms of Action | Clinical Application

During pregnancy, neurosteroids such as Allopregnanolone (3α,5α-tetrahydroprogesterone; 3α,5α-THP) or AlloP increase dramatically and rapidly decline following the baby’s birth.

Brexanolone is an intravenous stabilised form of AlloP, which the FDA recently approved to treat postpartum depression.

Zuranolone is an oral medication which has a similar molecular profile to brexanolone.

Zuranolone has better oral bioavailability and thus does not have to be administered intravenously.

A recent phase 3, double-blind, randomised, placebo-controlled trial showed that Zuranolone improved both depressive and anxiety symptoms in postpartum depression (PPD), with a higher rate of concurrent remission at days 3, 15, and 45 compared than placebo. [Deligiannidis et al, 2023]

Zuranolone also improved insomnia and patient-reported functional health and well-being. [Deligiannidis et al, 2023]