Neuroactive steroids - new possibilities in the treatment of postpartum depression

Ceska Slov Farm. 2022 Fall;71(4):142-150.

Abstract

Pregnancy and postpartum period are associated with demanding physical and psychological changes that often lead to the development of psychological disorders. Depression is diagnosed in more than one in six women after childbirth. However, the prevalence of postpartum depression can be much higher because many cases are undiagnosed. In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis. A new drug used in the treatment of postpartum depression is brexanolone, which was registered by FDA in 2019. The advantage over conventional therapy is its rapid onset of action. The structure represents the neuroactive steroid - allopregnanolone, which acts as an agonist on the δ-subunit of the GABA receptor and improves the symptoms of postpartum depression. In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial. The steroid structure was chemically altered to improve bioavailability and create an oral dosage form. Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.

Keywords: allopregnanolone; brexanolone; ganaxolone; postpartum depression; zuranolone.

MeSH terms

  • Depression, Postpartum* / drug therapy
  • Female
  • Humans
  • Neurosteroids* / therapeutic use
  • Pregnancy
  • Pregnanolone / therapeutic use
  • Receptors, GABA / therapeutic use
  • Sertraline / therapeutic use

Substances

  • Neurosteroids
  • Receptors, GABA
  • Pregnanolone
  • Sertraline