One tocilizumab infusion for depression that antidepressants had not moved
- A four-week, double-blind, placebo-controlled trial at the Universities of Bristol and Cambridge randomized 30 adults with antidepressant-resistant depression and persistently raised hs-CRP (at least 0.3 mg/dL on two tests) to one infusion of tocilizumab, an interleukin 6 receptor blocker (8 mg/kg, maximum 800 mg), or saline (14 vs 16 people; 29 received an infusion). Published in JAMA Psychiatry, 2026;83(8):857-863, online 20 May 2026.
- The primary outcome, BDI-II somatic symptoms at day 14, did not differ between arms (adjusted mean difference -0.12; 95% CI -2.51 to 2.28). No result reached statistical significance; the study was not powered for it.
- At the final follow-up (day 28), remission was reached by 7 participants (53.9%) on tocilizumab vs 5 (31.3%) on placebo (NNT 5), and response by 6 (46.2%) vs 3 (18.8%) (NNT 4).
- Baseline hs-CRP, but not baseline IL-6, tracked how much depression improved. There were no serious adverse events.
A small trial in Bristol and Cambridge gave 30 adults whose depression had not yielded to antidepressants a single infusion of tocilizumab, which blocks the interleukin 6 receptor, or saline. The authors describe it as the first randomized test of this mechanism in depression, and they ran it as a proof of concept.
Who was enrolled
Entry required ICD-10 moderate-to-severe depression despite antidepressant treatment, hs-CRP of at least 0.3 mg/dL on two tests with no infection, and a BDI-II somatic score of 7 or more. Everyone was taking an antidepressant, and 25 of 30 (83.3%) had more than two earlier episodes. Women made up 24 (80.0%). Mean baseline hs-CRP was 1.02 mg/dL on tocilizumab and 0.90 mg/dL on placebo.
Day 14, day 28 and CRP
At day 14 the somatic score was flat between arms. Improvement on tocilizumab accumulated over the following weeks, with the largest gaps at day 28 in somatic symptoms, depression severity, fatigue and anxiety. Remission and response rates at that point favored tocilizumab, with confidence intervals that include no difference. The higher the baseline hs-CRP, the larger the apparent benefit; IL-6 showed no such pattern.
A different question for the client who has tried everything
The sample was chosen for body-heavy symptoms and a raised CRP, so the trial says nothing about depression without them. Still, it gives a practical reason to ask about the body. A client on their third or fourth antidepressant, with fatigue, aches and heaviness that never lift, may be describing something other than a drug that failed. Ask when the symptoms started, whether they fluctuate, and whether a physician has ever checked CRP, and repeated it. Take the answer to the prescriber or the GP. Tocilizumab is not a treatment for depression, and nothing here changes your role.
For the client who has tried everything, persistent fatigue and bodily heaviness may be a prompt to ask about inflammation rather than to change the antidepressant again.
Thirty participants, one infusion, four weeks of follow-up, and a sample that was 80% women and selected for raised CRP and somatic symptoms. The study was not powered to detect statistical significance, and its confidence intervals include no effect.