Scientists May Have Found a Completely New Way To Treat Depression

Scientists may have found a completely new way to treat depression by targeting inflammation instead of brain chemistry.

A small clinical trial led by researchers at the University of Bristol suggests that targeting the immune system could help people with depression who do not improve with standard antidepressant medications. The findings, published May 20 in JAMA Psychiatry, provide early evidence that an existing anti-inflammatory drug may reduce symptoms in some patients with treatment-resistant depression.

The study examined tocilizumab, a medication commonly prescribed for immune-related conditions such as rheumatoid arthritis. Researchers wanted to determine whether the drug could improve depression symptoms in people whose condition had not responded to conventional treatments.

Although the trial included only 30 participants with moderate-to-severe depression, the results indicate that people who received tocilizumab experienced improvements in depression symptoms, anxiety, fatigue, and overall quality of life compared with those who received a saltwater placebo.

Depression and Inflammation

Most current antidepressants work by affecting brain chemicals such as serotonin, norepinephrine, and dopamine. However, these treatments are not effective for everyone. About one-third of people with depression fail to experience meaningful improvement with existing medications.

Growing evidence suggests that inflammation may contribute to depression in some individuals. Researchers estimate that roughly one-third of people with depression show signs of increased inflammation in blood tests, raising the possibility that an overactive immune system may play a role in their symptoms.

Previous studies have also found elevated levels of inflammatory proteins known as cytokines in people with depression. One cytokine that has drawn particular attention is interleukin 6 (IL-6), which plays an important role in the body’s inflammatory response.

Earlier research conducted by the same team used Mendelian randomization to investigate the relationship between inflammation and depression. This approach uses naturally occurring genetic differences across large populations to help distinguish cause-and-effect relationships from simple associations. Findings from Mendelian randomization studies, together with evidence from long-term population studies, have consistently pointed to the IL-6 inflammatory pathway as a potential contributor to depression.

Testing an Immune-Based Depression Treatment

Based on this evidence, researchers explored whether blocking the IL-6 pathway could improve symptoms in people whose depression was associated with inflammation.

The pilot study enrolled 30 participants with moderate-to-severe depression who had not responded well to antidepressant treatment. All participants also showed signs of low-grade inflammation in two separate blood tests taken two weeks apart.

Participants were randomly assigned to receive either tocilizumab (14 people) or a placebo (16 people). Researchers then monitored them for four weeks to assess changes in symptoms and overall well-being.

Because the study was relatively small, researchers found limited statistical evidence for significant differences between the two groups. However, participants treated with tocilizumab appeared to improve more over time across several measures, including depression severity, fatigue, state anxiety, and quality of life.

The researchers also found that remission rates were higher among those who received tocilizumab. Depression remission occurred in 54% of participants in the treatment group compared with 31% in the placebo group. This corresponds to a Number Needed to Treat (NNT) of 5, meaning an additional 5 patients will need to be treated to make one patient better. By comparison, the NNT for SSRIs, the most commonly prescribed first-line antidepressants for moderate-to-severe depression, is approximately 7.

Toward More Personalized Depression Care

Golam Khandakar, Professor of Psychiatry and Immunology from the MRC Integrative Epidemiology Unit (MRC IEU) at the University of Bristol and NIHR Biomedical Research Centre: Bristol (NIHR BRC: Bristol), and the study’s senior author and chief investigator, said: “This work represents an important milestone in the development of new treatments for depression especially difficult-to-treat depression, which affects millions of people in the UK alone.”

“This is one of the first randomized controlled trials to test immunotherapy for depression, the first to test IL-6R as the treatment target, and the first to use a targeted approach to select patients most likely to benefit, and to show that it works.”

Dr. Éimear Foley, Senior Research Associate in Immunopsychiatry at Bristol’s MRC IEU and the NIHR BRC: Bristol, and the study’s lead author, added: “Depression is estimated to affect around 10-20% of people worldwide during their lifetime, yet for many patients current treatments do not work well enough.”

“Our study moves us closer to more tailored depression care, where treatments are chosen to better fit a person’s biology. This will help us to provide the right treatment to the right patients at the right time.”

One participant who took part in this study said: “I was happy to take part. Without research, advancements in medicine cannot be made.”

Larger Trial Planned

Researchers emphasize that larger studies are needed before immunotherapy could become a standard treatment for depression. The next step will be a large phase III randomized controlled trial designed to provide the stronger evidence needed for doctors to potentially prescribe immunotherapy for depression in clinical practice.

Reference: “Interleukin 6 as a Treatment Target for Depression: A Proof-of-Concept Randomized Clinical Trial” by Éimear M. Foley, Nicholas Turner, Ruta Margelyte, Hannah J. Jones, Muzaffer Kaser, Glyn Lewis, Peter B. Jones and Golam M. Khandaker, 20 May 2026, JAMA Psychiatry.
DOI: 10.1001/jamapsychiatry.2026.1053

The double-blind proof-of-concept randomized controlled trial recruited 30 participants through the University of Cambridge and the Cambridgeshire and Peterborough NHS Foundation Trust. Participants were followed for four weeks after treatment.

The research was funded by Wellcome, with additional support from the NIHR BRC: Bristol, NIHR BRC: Cambridge, and the BMA Foundation J Moulton grant.

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