Depression Franchise

Sage is seeking to shift how certain mood disorders are understood and treated.

Sage is exploring new disease pathways for certain depressive disorders where there is a high unmet need for additional treatment options. We are working to understand the underlying mechanisms for numerous disorders of the brain to help us develop therapies that may address current treatment gaps for patients. We aim to change the possibilities for people with brain health disorders by making medicines that matter and creating a new understanding that depressive disorders are medical conditions that should be treated with urgency.

We focus our research and development efforts on modulation of GABA and NMDA receptors, two critical neurotransmitter systems that have responsibility for information flow within the intricate circuits of the brain and central nervous system. Both GABA and NMDA systems contribute significantly to regulating CNS function. However, dysfunction in these two systems is known to be at the core of numerous psychiatric disorders. Navigating these complex circuits is a challenge, but a welcome opportunity for the teams at Sage as we seek to provide new treatment options for patients.

We are using our unique development approach to evaluate our investigational drug candidates in postpartum depression (PPD) and major depressive disorder (MDD).

Postpartum Depression

Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy.1-7 During pregnancy, levels of certain hormones rise and then rapidly fall after giving birth. These hormone shifts may put some women at risk for developing this serious disorder.

Postpartum depression can have devastating consequences for a woman and for her family, which may include significant functional impairment, depressed mood and/or loss of interest in her newborn, and associated symptoms of depression such as loss of appetite, difficulty sleeping, worry or feeling overly anxious, motor challenges, lack of concentration, loss of energy and poor self-esteem.

Sage’s lead product is approved by the U.S. FDA for the treatment of postpartum depression in adults. We are also developing another product candidate in collaboration with Biogen, zuranolone (SAGE-217), as a potential treatment for postpartum depression as part of our broader depression program. Zuranolone (SAGE-217) is an investigational drug and is not approved by any Health Authority.

Major Depressive Disorder

Major depressive disorder is a common but serious mood disorder, often affecting how a person feels, thinks, and handles daily activities. Generally thought of as a chronic condition, it’s characterized by episodes of depressed mood, feelings of hopelessness, anxiety, loss of energy and sleeping difficulties. Major depressive disorder can be life-threatening. It is estimated that more than 19 million adults in the U.S. and more than 260 million people worldwide suffer from depression. 8,9

While antidepressants are widely used for treatment, results from large scale studies suggest the need for additional treatment options.10,11 GABA modulation is being studied as a new possible mechanism of action for treating episodic depression.12-14 We are evaluating zuranolone (SAGE-217), a once-daily, two-week, investigational drug in development for the treatment of MDD. Zuranolone is an investigational oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM).


  1. Ko JY et al. MMWR Morb Mortal Wkly Rep. 2017;66:153-158.
  2. Hamilton BE et al; National Center for Health Statistics. Births: Provisional data for 2018. Vital Statistics Rapid Release; no 7. Published May 2019. Accessed July 9, 2019.
  3. DeSisto CL et al. Prev Chronic Dis. 2014;11:E10.
  4. Centers for Disease Control and Prevention. Updated June 12, 2018. Accessed July 9, 2019.
  5. Centers for Disease Control and Prevention. Updated February 28, 2019. Accessed July 15, 2019.
  6. Roberts JM et al; American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy. Published 2013. Accessed July 9, 2019.
  7. Callaghan WM et al. Am J Obstet Gynecol. 2010;202(4):353.e1-6.
  8. Center for Behavioral Health Statistics and Quality. (2020). Results from the 2019 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration. Retrieved from
  9. Depression and Other Common Mental Disorders: Global Health Estimates. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO
  10. Trivedi MH, et al., Am J Psychiatry, 2006,163:1, 28-40
  11. Rush AJ et al., Am J. Psychiatry, 2006,163:11, 1905-1917
  12. Uzunova et al., PNAS, 1998
  13. Luscher et al, Molecular Psychiatry, 2011
  14. Schule et al, Progress in Neurobiology, 2014