Essential Reads: Investigational Treatment of Depressive Disorders With Neuroactive Steroids: Potential Implications for PMDD

Neuroactive steroids or neurosteroids are a new class of medications which appear to have anxiolytic and antidepressant effects and have received a great deal of attention over the past few years.  Most of neuroactive steroids currently under investigation as antidepressants are derivatives of allopregnanolone.  In the human body, the hormone progesterone is metabolized into a variety of active and inactive compounds, including allopregnanolone.  It is hypothesized that these allopregnanolone derivatives ameliorate anxiety and depressive symptoms by modulating the hypothalamic-pituitary-adrenal or HPA axis which mediates the body’s response to stress and is modulated by GABAergic signaling.

The first neurosteroid to generate a great deal of excitement was brexanolone which was approved by the FDA for the treatment of postpartum depression.  Zuranolone, which is similar to brexanolone but can be administered orally, appears also to be effective for the treatment of postpartum depression.  And the neurosteroid ganaxolone shows promised for the treatment of perimenopausal depression.  

In an article published in the Journal of Clinical Psychiatry, Mercedes Szpunar, MD and Marlen Freeman, MD, review data supporting the use of similar neurosteroids for the treatment of premenstrual dysphoric disorder.  

Szpunar MJ, Freeman MP.  Investigational Treatment of Depressive Disorders With Neuroactive Steroids: Potential Implications for Premenstrual Dysphoric Disorder.  J Clin Psychiatry. 2021 Jun 8;82(4):20ac13853. Free article.