Major depressive disorder and pain are two serious mental and physical health conditions affecting millions of people in the United States and around the world. The two conditions often co-occur and negatively influence each other. Although there are currently psychotropic medications for depression and drugs that help to alleviate pain, they come with side effects ranging from unpleasant to life-threatening. It is therefore of great importance to find alternative treatments that are safer and effective, with few to no side effects. Research is underway examining the effectiveness of neurosteroids for major depressive disorder and chronic pain.
Neurosteroids
Neurosteroids are endogenous steroids or molecules within the central nervous system that regulate neurotransmission among many targets including gamma-aminobutyric acid (GABA) receptors which play a crucial role in inhibiting signaling in the brain. Science has found that the interaction between neurosteroids and GABA receptors positively impacts mood, pain, cognition, stress as well as providing neuroprotection.
Endogenous and Exogenous Neurosteroids
Endogenous steroids are vital for mood and emotional well-being, among them, allopregnanolone or alloP, which is derived from progesterone, has been found to be effective in treating postpartum depression. Exogenous steroids are synthetically created versions of neurosteroids that naturally occur in the brain. Two such steroids have been created to treat postpartum depression – Brexanolone and Zuranolone. Brexanolone has been found to have serious adverse effects, must be administered in a health care facility, carries risk for abuse and causes severe central nervous depression. This article focuses instead on Zuranolone.
Zuranolone
Zuranolone is a synthetically created version of allopregnanolone which targets GABAA receptors and has shown good results as a rapid, 14-day treatment for postpartum depression. It was approved by the FDA in 2023 and is marketed under the brand name Zurzuvae. It is easier to take because it comes in a pill form and carries less serious but still negative side effects including gastrointestinal upset, sedation, headaches, upper respiratory problems and vertigo. It is not recommended for pregnant women. It also is being considered as a treatment for major depressive disorder, pain, insomnia, Parkinson’s tremor and bipolar disorder.
Final Thoughts on Neurosteroids, Major Depressive Disorder and Pain
Major depression and pain often go hand-in-hand, so finding a safer treatment is important. Neurosteroids have shown positive results in modulating pain perception by interacting with GABA receptors while at the same time effectively treating symptoms of major depressive disorder. Further research in the effects of neurosteroids may create a new approach to treating two difficult health conditions that impair quality of life. More research is required to examine efficacy, safety and optimal dosing.
Reference
Haan, Meghan. 2024. Neurosteroids for the Treatment of Major Depressive Disorder (MDD) and Chronic Pain. College of Pharmacy and Allied Professions. South Dakota University.