Drug Treating Post-Partum Depression Acts on Inflammation

New research has found that a drug called brexanolone used for treating post-partum depression works by inhibiting systemic inflammatory pathways.

Post-partum depression (PPD) develops after childbirth and affects both the mother's and the infant's health by preventing healthy bonding. Women with PPD experience intense anxiety, feelings of depression, sleeplessness, inability to care for their children, and risk for suicide.

Brexanolone, an IV infusion comprised of a derivative of progesterone, was approved by the U.S. Food and Drug Administration for the treatment of PPD in 2019. The fast-acting medication significantly reduces depression symptoms and provides effects for up to 90 days. However, exactly how the drug provides these therapeutic effects has remained a mystery – until now.

Uncovering the Role of Brexanolone and Inflammation in Post-Partum Depression

A research team at the UNC School of Medicine has found that brexanolone works within the body by inhibiting the key systemic inflammatory pathways that are associated with depression. The new finding is monumental in that it suggests that PPD is likely caused, at least in part, by inflammation.

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‘Brexanolone inhibited the toll-like receptors responsible for the production of the markers of inflammation in post-partum depression.’

They found that brexanolone inhibited the toll-like receptors responsible for the production of cytokines and chemokines - the markers of inflammation. Toll-like receptors are like gatekeepers on the surface of cells, recognizing molecules and then initiating a cell’s inflammatory response.

These results provide the first human data showing that blockade of specific inflammatory pathways is likely involved, at least in women who were unresponsive to other medications. Their results were published in eBioMedicine.

According to recent studies, one in eight women experience post-partum depression symptoms, and the prevalence of depression diagnoses at delivery is rising. The CDC reports that rates in 2015 were seven times higher than they were in 2000. However, scientists are still unsure of what causes PPD to develop in the brain.

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One potential cause of PPD could be a deficiency in GABAergic transmission, which calms the brain via a neurotransmitter known as GABA. GABA, or y-Aminobutyric acid, is found in our central nervous systems and instructs our bodies to stop, or inhibit, the activity of neurons. Additionally, PPD could also be caused by deficits in our normal responses to stress.

But recent data and this new study suggest that inflammation may be contributing to the syndrome. Much like other types of depression, PPD is typically treated with SSRIs, but sometimes patients don't improve with conventional therapy.

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Introduction

Postpartum depression (PPD) is a condition faced by mothers following childbirth. It is characterized by severe mood swings, restlessness, difficulty deciding, difficulty bonding with the baby, crying, disturbed sleep and appetite, lack of motivation, fatigue, negative thought patterns, anxiety and thoughts of harming the baby or oneself.

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Baby blues or postpartum dysphoria is a less intense version of the same that lasts for a shorter time and is seen in 50% to 75% of women. PPD is seen in about 17% of women. It is caused by both physical and emotional factors. Early interventions help to manage the condition.

Now, doctors can prescribe brexanolone in such circumstances. Brexanolone was initially approved in 2019, but the mechanism underlying its antidepressant action was unclear at the time.

By the same reasoning, brexanolone or other anti-inflammatory drugs may also be effective for treating other types of depression that elevate inflammatory markers. The team hopes that their new findings may lead to more cost-effective treatments that can block the same inflammatory pathways that were identified in the study.

Source-Eurekalert