Bench-to-bedside: NIMH research leads to brexanolone, first-ever drug specifically for postpartum depression

What

Approximately 1 in 9 women in the United States experiences symptoms of postpartum depression, according to the Centers for Disease Control and Prevention(link is external). Now, the U. S. Food and Drug Administration (FDA) has approved brexanolone(link is external), an analog of the endogenous human hormone allopregnanolone and the first drug specifically designed to treat postpartum depression.

Some psychiatric drugs owe their discovery to chance – serendipitous observations of clinical benefit – or a process of incremental improvement based on drugs previously discovered by chance. Not so with brexanolone, which has a truly novel mechanism of action and was developed by design, thanks to a series of basic and translational neuroscience studies. FDA approval represents the final phase of a bench-to-bedside journey for this drug — a journey that began in the NIMH Intramural Research Program (IRP).

In the 1980s, NIMH IRP researchers discovered that metabolites (products formed when the body breaks down or “metabolizes” other substances) of the steroid hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA)—a major inhibitory neurotransmitter in the brain. These steroids were found to amplify GABA-activated chloride ion currents, thereby impacting the excitability of neurons.

This finding led to a series of studies, completed by researchers in the NIMH IRP and by researchers at institutions funded by NIMH, that clarified how these metabolites fluctuate during times of stress and during the estrous cycle in rats and the menstrual cycle in humans. Research indicated that the concentration of one of these metabolites (allopregnanolone) increases during pregnancy, but then drops after birth. In some women, this drop triggers the development of depression and anxiety.

A biopharmaceutical company utilized these basic research findings to develop brexanolone, a drug that can be used to treat postpartum depression by restoring levels of this metabolite. Successful clinical trials have led to FDA approval of an injectable version of this drug(link is external).

Want to learn more about this story? NIMH experts are available to provide information on postpartum depression and the importance of, and the science underlying, brexanolone.

Who

Joshua Gordon, M.D., Ph.D., NIMH Director
Peter Schmidt, M.D., Chief of the Behavioral Endocrinology Branch, part of NIMH IRP
Mi Hillefors, M.D., Ph.D., Chief of the Translational Therapeutics Program, part of the NIMH Division of Translational Research

For interviews, photos, or additional background information, please contact the NIMH Press Office at 301-443-4536 orNIMHpress@nih.gov(link sends e-mail).

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible

About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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