Major depressive disorder (MDD) is a widespread and serious mental health condition that affects how people think, feel, and function in daily life. It is already a leading cause of disability, and researchers expect it to become the most common and costly illness worldwide by 2030. While many medications are available to treat depression, finding the right one remains difficult. Nearly one-third of patients do not improve after trying their first antidepressant, often leading to months of trial and error.

One reason for this challenge is the lack of clear, objective tools that can help doctors predict which treatment will work best for a specific person. Most treatment decisions are still based on symptoms, medical history, and experience rather than biological markers. A recent study published in General Psychiatry set out to explore whether traditional Chinese medicine (TCM) could offer new insights into treating MDD and whether brain imaging could help predict treatment response.

Testing a Traditional Remedy Against a Standard Antidepressant

The researchers conducted a randomized, double-blind, placebo-controlled clinical trial involving 28 outpatients diagnosed with MDD at the Fourth People's Hospital of Taizhou. In a randomized trial, participants are assigned to treatment groups by chance. Double-blind means neither the patients nor the researchers knew who received which treatment, helping reduce bias. A placebo-controlled design allows scientists to compare real treatment effects against inactive substitutes.

Participants were divided into two groups. One group received Yueju Pill, a traditional Chinese herbal medicine, along with a placebo for escitalopram. The second group received escitalopram, a commonly prescribed antidepressant, along with a placebo for Yueju Pill. This design allowed researchers to directly compare the two treatments under similar conditions.

To track outcomes, the team measured depression severity using the 24-item Hamilton Depression Scale (HAMD-24), a widely used clinical questionnaire. They also collected peripheral blood samples and performed MRI brain scans to examine changes in brain structure and biology.

Brain Chemistry and Structural Networks Tell Different Stories

After treatment, both groups showed improvements in their depression symptoms, suggesting that Yueju Pill and escitalopram were similarly effective at reducing clinical signs of depression. However, a key biological difference emerged. Only patients in the Yueju Pill group experienced a significant increase in serum brain-derived neurotrophic factor (BDNF), a protein that supports brain cell growth, connectivity, and mood regulation. Lower BDNF levels have previously been linked to depression, making this finding especially notable.

The brain imaging data revealed even deeper insights. Researchers found that specific networks formed by brain structures could predict changes in depression scores in both treatment groups. These networks reflect how different brain regions are organized and connected.