Immunotherapy could offer an entirely new way to treat patients with hard-to-treat depression, according to a clinical trial led by the University of Bristol. JAMA Psychiatry May 20th.
In this small pilot study, researchers tested whether tocilizumab, a drug commonly prescribed for inflammatory conditions such as rheumatoid arthritis, could reduce symptoms of depression in patients who had not improved with standard antidepressants.
Although the trial included only 30 participants with moderate to severe depression, the study results suggest that the drug may help reduce depression severity, anxiety, and fatigue while improving quality of life.
Scientists investigate the role of inflammation in depression
Most current antidepressants work by targeting brain chemicals such as serotonin, dopamine, and norepinephrine. However, about one-third of people with depression respond poorly to these drugs.
In recent years, scientists have increasingly focused on another possible cause of depression: inflammation. Studies show that about one in three people with depression have elevated inflammatory markers in their blood, suggesting that the immune system may play a role in triggering symptoms in some patients.
One inflammatory protein that has received particular attention is interleukin-6 (IL-6), which helps regulate the body’s immune response. Previous studies have linked elevated IL-6 levels to depression.
Previous research by the same team used Mendelian randomization, a genetic research technique that helps scientists distinguish between cause and chance and investigate associations. Their findings suggested that inflammation involving the IL-6 pathway may be one of the biological factors of depression.
Conducting clinical trials of existing arthritis treatment drugs
To find out whether blocking IL-6 could improve symptoms of depression, researchers began a four-week randomized controlled trial in patients with treatment-resistant depression who also showed signs of mild inflammation in blood tests.
Thirty participants were recruited through the University of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust. 14 received tocilizumab and 16 received saline placebo. Participants were monitored over a four-week period to track changes in symptoms.
The researchers said that because the study was relatively small, there was limited statistical evidence of significant differences between the two groups. Still, people who received tocilizumab generally showed significant improvements over time in several areas, including depression severity, fatigue, anxiety, and overall quality of life.
Remission rates were also higher in the treatment group. The researchers reported that 54% of participants who took tocilizumab achieved remission of depression, compared with 31% in the placebo group. The number needed to treat (NNT) was calculated as 5. This means that five people would need treatment for one more person to benefit. For comparison, SSRIs, the most commonly prescribed antidepressants for moderate to severe depression, have an NNT of approximately 7.
Personalized depression treatment could be the future
Golam Khandakar, Professor of Psychiatry and Immunology at the University of Bristol’s MRC Integrated Epidemiology Unit (MRC IEU) and Bristol NIHR Biomedical Research Center (NIHR BRC), and senior author and principal investigator on the study, said: “This study marks an important milestone in the development of new treatments for depression, particularly hard-to-treat depression that affects millions of people worldwide.” Only in England. ”
“This is one of the first randomized controlled trials to test immunotherapy for depression, the first to test IL-6R as a therapeutic target, and one of the first to use a targeted approach to select the patients most likely to benefit and show that it works.”
Dr Eimear Foley, senior research fellow in immunopsychiatry at Bristol’s MRC IEU and Bristol NIHR BRC and lead author of the study, added: “Depression is estimated to affect around 10-20% of people worldwide at some point in their lives, but for many patients current treatments are not fully effective.”
“Our research brings us closer to more tailored depression treatments, where treatments are selected based on an individual’s biological characteristics. This will help us get the right treatment to the right patient at the right time.”
One participant in the study said, “I was happy to be able to participate.Without research, medical progress would not be possible.”
Large-scale clinical trials are planned
The researchers emphasize that larger studies are needed before immunotherapy becomes a standard treatment for depression. The next step will be a large phase III randomized controlled trial designed to determine whether doctors should start prescribing immunotherapy for depression more widely.
This research was funded by Wellcome, with additional support from NIHR BRC: Bristol, NIHR BRC: Cambridge, and a BMA Foundation J Moulton grant.
