A Promising New Target for Treatment-Resistant Depression

A small pilot trial suggests that tocilizumab, an anti-inflammatory drug, may help some patients with depression who have not responded to standard antidepressants.

"This is one of the first randomized controlled trials to test immunotherapy for depression and the first to test IL-6R as a treatment target."
— Professor Golam Khandaker, University of Bristol

Study Design and Participants

The trial, published in JAMA Psychiatry on May 20, was a double-blind, placebo-controlled, proof-of-concept study. Researchers enrolled 30 adults diagnosed with moderate-to-severe depression who had not responded to standard antidepressants. All participants were required to have low-grade inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) levels of 0.30 mg/dL or greater, confirmed by two blood tests taken two weeks apart.

Participants were randomly assigned to receive a single intravenous dose of tocilizumab (8.0 mg/kg, n=14) or a saline placebo (n=16). Outcomes were assessed at baseline and at 1, 2, and 4 weeks following the infusion.

Key Results

Primary Outcome: At day 14, the primary outcome—measuring somatic symptoms—showed little statistical difference between the tocilizumab and placebo groups.

Depression Severity and Symptoms: Compared to the placebo group, the tocilizumab group showed greater stepwise improvements over time in depression severity, fatigue, anxiety, and quality of life. No improvement was observed in cognition.

Remission and Response Rates:

• At 4 weeks, 54% of participants in the tocilizumab group achieved depression remission, compared to 31% in the placebo group (risk difference 0.2).
• 46% of participants in the tocilizumab group showed a treatment response, compared to 19% in the placebo group (risk difference 0.2).

Number Needed to Treat (NNT): The NNT for tocilizumab was 5. For comparison, the NNT for standard SSRIs is approximately 7.

Correlation: Improvements were found to correlate with baseline hs-CRP levels rather than interleukin-6 (IL-6) levels.

Safety

No serious adverse events were reported during the study, and no participants withdrew from the trial.

Limitations and Context

The study was small (n=30) and was not statistically powered to yield definitive conclusions. The results were not statistically significant. The authors describe it as a proof-of-concept trial and state that larger, longer trials are needed to confirm the findings.

Background

Approximately one in three people with depression do not respond to current treatments, which primarily target brain chemicals such as serotonin. About one in six adults in the UK experience moderate to severe depressive symptoms in their lifetime.

Previous observational and genetic studies (Mendelian randomization) have suggested that inflammation, particularly the interleukin-6 (IL-6) pathway, may play a causal role in depression for a subset of patients.

Tocilizumab is an immunosuppressive drug that blocks the IL-6 receptor (IL-6R), preventing inflammatory signals. It is currently approved for the treatment of autoimmune conditions such as rheumatoid arthritis.

Statements from Researchers

"This research moves toward more tailored depression care, where treatments are chosen based on a person's biology."
— Dr. Éimear Foley, co-author and lead author

Next Steps

A larger phase III trial is planned to provide definitive evidence of efficacy and to potentially enable clinical prescription of tocilizumab for depression.