Immunotherapy Shows Promise for Treatment-Resistant Depression in Early Trial

Immunotherapy could offer a new treatment option for depressed patients who do not respond to conventional antidepressants, according to results from an early clinical trial published by University of Bristol researchers.

The study investigated whether tocilizumab, an anti-inflammatory drug commonly prescribed for rheumatoid arthritis and other immune conditions, could alleviate symptoms in patients with difficult-to-treat depression.

Roughly one in three people with depression fail to improve with standard treatments, which target brain chemicals. About one in six UK adults will experience moderate to severe depressive symptoms during their lifetime.

Tocilizumab blocks the IL-6 receptor, preventing it from binding to cells and halting inflammatory signals linked to autoimmune disorders.

The trial enrolled 30 participants with moderate to severe depression who had not responded adequately to standard antidepressants. They were randomly assigned to receive either tocilizumab or a placebo over four weeks.

While the small study found little statistical evidence of a significant difference between the groups, those receiving tocilizumab showed greater improvement over time across multiple measures, including overall depression severity, fatigue, anxiety and quality of life.

Dr. Golam Khandaker, professor of psychiatry and immunology at Bristol Medical School and senior author, called the trial an “important milestone” in developing new therapies for particularly hard-to-treat depression.

“This is one of the first randomised 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,” added Khandaker, an investigator at the MRC Integrative Epidemiology Unit.

Participants treated with tocilizumab achieved depression remission at a rate of 54%, versus 31% in the placebo group. The number needed to treat (NNT) was 5, meaning five patients would need treatment for one to benefit. By comparison, the NNT for SSRIs, the most common first-line antidepressants, is about 7, suggesting immunotherapy could be more effective.

The researchers cautioned that the trial involved a small number of participants but said it provides early evidence that immunotherapy could help reduce depressive symptoms.

“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,” said Dr. Éimear Foley, a senior research associate in immunopsychiatry at the MRC Integrative Epidemiology Unit and co-author.

“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.”