On August 4, 2023, the United States FDA approved Zuranolone (Zurzuvae) as the first oral neurosteroid treatment for postpartum depression (PPD) in women. Postpartum depression is a potentially life-threatening condition that occurs after a woman gives birth and can cause new mothers to feel extreme sadness, anxiety, despair and, in extreme cases, thoughts of harming themselves or their children.
Dr. Samba Reddy, an Indian citizen and Telugu-origin Scientist, who is working at Texas A&M University School of Medicine, has made groundbreaking contributions to neurosteroid replacement therapy (NRT) research, paving the way for the development of this new therapeutic medication for PPD.
Neurosteroids are steroids that are produced in the brain and have significant regulatory effects on brain function. Reddy explains that “These neurosteroids are released each time we go undergo mild stress, and that means that they are ‘stress-busters.’” During pregnancy, one particular neurosteroid, allopregnanolone, is produced in greater quantities, but after labor and delivery, neurosteroid levels fall, causing chemical imbalances in the brain that might result in PPD, according to Dr. Reddy’s paper was published in the August 2023 issue of the journal Trends in Molecular Medicine.
Citing the examples of hormone replacement therapy for menopausal women or insulin replacement therapy for diabetics, Dr. Reddy pondered, “Why don’t we replace the allopregnanolone to compensate for the loss of naturally occurring levels to combat these symptoms of PPD?” This question led to the development of intravenous allopregnanolone for the treatment of PPD.
This medicine, renamed brexanolone, was approved in 2019 as the first PPD treatment to be administered in certified health facilities. This landmark journey on brexanolone, from concept to clinic, was archived in the journal Psychopharmacology.
“Ten percent of mothers experience PPD, but before NRT-based neurosteroid therapeutics, we didn't have any medicine that worked rapidly,” Dr. Reddy said. “After childbirth, they would have to wait weeks for existing antidepressants, such as fluoxetine or other SSRIs or SNRIs, to take effect, so the neurosteroid therapy is filling this gap.”
The treatment takes effect within just a few hours, which is in stark contrast to the traditional antidepressants that have been historically used to treat PPD, which take three or four weeks.
However, he explained that since the previously approved brexanolone was an intravenous medication, people had to stay at the hospital for three days to get the infusion, and accessibility was limited due to time, financial, and social constraints.
Zuranolone, an oral allopregnanolone analog, alleviates some of these issues by being administered by mouth in a single 14-day course. This allows new mothers to take the medication and recover in the comfort of their own home.
Similar to brexanolone, it replaces the loss of natural neurosteroids and improves the function of the extrasynaptic and synaptic GABA-A receptors, which regulate mood and behavior.
“I have spent 25 years of my life just researching neurosteroids. My job is to create new knowledge. I have created dozens of new pieces of knowledge, and some remain as ideas, some only become papers, and some turn into clinical products,” Reddy said. With publications going back as far as 1995 with the concept of “Neurosteroids: a new class of neuromodulators,” published in the journal Drugs Today (1995), his research on neurosteroid therapies has gone through all of these phases.
The neurosteroid concept he and his collaborators came up with over two decades ago has finally enabled the creation of a new type of product that is accessible to the public as zuranolone.
Throughout his career, Dr. Reddy has made stellar contributions to the development of new brain disease therapies, as recognized by the Texas A&M Innovation office, which featured him as the Inventor of the Month in September 2023.
The clinical approval of zuranolone recognizes Dr. Reddy’s pioneering research on neurosteroids, the endogenous molecules that regulate neuronal excitability, seizure and mood by rapidly interacting with ionotropic GABA-A receptors on neurons. Now, he will be able to see this medication on the pharmacy shelf because of the fruition of his decades of painstaking work in unravelling the cellular mechanisms behind neurosteroid effects in the brain.
The success of Dr. Reddy’s pioneering research on neurosteroids has ushered in a new era of research with the potential to develop new treatments for other neurological and psychiatric conditions.