Immunotherapy for Depression: New Trial Tests Tocilizumab (Actemra)

Immunotherapy for depression is an experimental treatment approach that targets the immune system instead of brain chemistry alone. Rather than boosting serotonin or other neurotransmitters, these treatments use biologic drugs to block specific inflammatory signals in the body that may fuel depressive symptoms.

The need for new options is necessary. Research on treatment-resistant depression indicates that roughly one third of people with depression do not respond adequately to standard antidepressants. For this group, scientists have been searching for entirely new biological targets, and inflammation has emerged as one of the most promising.

It is important to note that immunotherapy is not an approved depression treatment. It is currently available only within clinical trials, but the recent findings are an early proof of concept that may lead to further clinical trials or approved treatments.

A growing body of evidence suggests that, for a meaningful subset of people, inflammation is not just a bystander in depression but an active driver. A systematic review of 37 studies found that about one in four people with depression show low-grade inflammation on blood tests measuring C-reactive protein, and over half show at least mildly elevated levels.

One inflammatory protein has drawn particular attention: interleukin 6, or IL-6, a signaling molecule that helps regulate the immune response. Higher IL-6 levels have repeatedly been associated with depression, and Mendelian randomization research, a genetic method that helps separate cause from coincidence, supports the possibility that IL-6 signaling plays a causal role rather than simply appearing alongside the illness.

This may help explain why depression so often comes with physical symptoms such as fatigue, low energy, and disrupted sleep. Inflammation can affect the whole body, and for people whose depression has an inflammatory component, calming that response may relieve both mood and physical symptoms.

Tocilizumab, sold under the brand name Actemra, is a biologic drug that blocks the IL-6 receptor. It is FDA approved for inflammatory conditions such as rheumatoid arthritis, but it has never been an approved treatment for any mental health condition. The new trial tested whether it could become one.

The University of Bristol-led study enrolled 30 adults with moderate to severe depression that had not responded to standard antidepressants. Importantly, every participant also showed signs of low-grade inflammation on blood testing, a selection strategy that set this trial apart from earlier research. Fourteen participants received a single intravenous infusion of tocilizumab, while sixteen received a saline placebo, and all were followed for four weeks.

The results were notable for such a small study. In the tocilizumab group, 54% of participants achieved depression remission, compared to 31% in the placebo group. The number needed to treat was calculated at 5, meaning five people would need the treatment for one additional person to benefit. For context, that figure is around 7 for SSRIs, the most commonly prescribed antidepressants. Participants who received the drug also showed greater improvements in fatigue, quality of life, and anxiety measures.

The researchers were careful to note the limitations of this trial. With only 30 participants, there was limited statistical evidence of major differences between groups, and the trial was designed as a proof of concept rather than a definitive test.

The trial marks several firsts. It is among the first randomized controlled trials of immunotherapy for depression, the first to target the IL-6 receptor specifically, and the first to select participants based on their inflammation levels, choosing the patients most likely to benefit. The research team is now planning a large phase III randomized controlled trial to determine whether anti-inflammatory drugs for depression should ever be prescribed more broadly.

The bigger picture is a shift toward personalized psychiatry, where treatments are matched to a person’s biology instead of prescribed through trial and error. A simple inflammation blood test might one day help identify who is most likely to respond to an immune-targeting approach.

For now, caution is essential. Tocilizumab suppresses part of the immune system and carries real risks, including serious infections, so it should never be taken for depression outside a supervised clinical trial. Over-the-counter anti-inflammatory medications are not a depression treatment, and no one should stop or change a prescribed psychiatric medication without guidance from their provider.

While immunotherapy works its way through clinical trials, people with hard-to-treat depression do not have to wait on the science. Several evidence-based treatments are available right now and have helped many people find relief after multiple medications failed.

TMS, or transcranial magnetic stimulation, is an FDA-cleared, noninvasive treatment that uses magnetic pulses to stimulate underactive areas of the brain involved in mood regulation. Spravato, an esketamine nasal spray administered under medical supervision, is FDA approved specifically for treatment-resistant depression. Beyond these, a psychiatrist can adjust medications, add augmentation strategies, and pair treatment with therapy to improve outcomes.

These options can make a meaningful difference. One patient success story shows what recovery from treatment-resistant depression can look like with the right combination of care, even after years of setbacks.

The tocilizumab trial offers new understanding about what can drive depression, and may eventually add another tool to the treatment landscape. Until then, proven help exists today, and reaching out to a mental health professional is the first step toward finding the approach that works.

Tocilizumab (Actemra) is FDA approved for certain inflammatory conditions but is not approved, offered, or prescribed by LifeStance for depression.