New treatment for depression targets immune system, not brain

In a small pilot study, researchers examined the effects of tocilizumab, a drug commonly used for inflammatory diseases including rheumatoid arthritis. The researchers wanted to find out whether the drug could relieve symptoms in patients who had not responded to standard antidepressants. The study involved 30 people with moderate to severe depression. The results showed that tocilizumab could potentially reduce the severity of depression, anxiety and chronic fatigue, as well as improve the quality of life of patients.

Most modern antidepressants act on brain neurotransmitters – serotonin, dopamine and norepinephrine. However, in about a third of patients such drugs are ineffective. In recent years, scientists have increasingly linked depression to inflammatory processes in the body. Research shows that about one in three people with the disorder have elevated levels of inflammatory markers in their blood, suggesting a possible role for the immune system in the development of symptoms.

Of particular interest to researchers is the protein interleukin-6 (IL-6), which is involved in the regulation of the immune response. Previous work has already linked elevated IL-6 levels to the development of depression. In previous studies, the same research team used Mendelian randomization, a genetic approach to distinguish causation from chance. The results suggested that inflammation involving the IL-6 pathway may be one of the biological mechanisms for the development of depression.

To test this hypothesis, the researchers conducted a four-week randomized controlled trial among patients with treatment-resistant depression and signs of chronic low-grade inflammation. Participants were recruited through the University of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust. Fourteen people received tocilizumab and sixteen received saline placebo. Over the course of four weeks, the researchers tracked changes in the participants’ mental states.

The authors of the work emphasize that due to the small sample size, statistically significant differences between the groups could not be identified. However, patients taking tocilizumab showed greater improvements in several measures, including severity of depression, anxiety, fatigue and overall well-being.

In addition, the remission rate was higher in the group receiving the drug: 54% of participants achieved remission versus 31% in the placebo group. The researchers calculated an NNT (number needed to treat) of 5. This means that treating five people would produce an additional benefit in one patient. For comparison, for common antidepressants of the SSRI class, this figure is about 7.