The Insight Study

A proof-of-concept, randomised, double blind, placebo controlled study of the effect of IL-6 inhibition in inflamed depression

Approximately a third of depressed patients do not respond to antidepressants; a third of depressed patients show evidence of low-grade systemic inflammation – this is unlikely to be a coincidence. Emerging evidence, including studies published by the InPsych group, indicates that low-grade systemic inflammation may contribute to pathogenesis of depression and may be associated with antidepressant resistance.

Low-grade systemic inflammation is reflected by elevated concentrations of circulating inflammatory markers in blood, such as proinflammatory cytokines (e.g., interleukin 6 or IL-6) and acute phase proteins (e.g., C-reactive protein or CRP). Concentrations of these inflammatory markers are elevated in patients with depression, which tend to normalise after recovery but continue to be elevated in patients with depression who do not improve with antidepressant treatment. We have previously shown that elevated concentrations of IL-6 and CRP in childhood/adolescence are associated with increased risk developing depression and psychosis subsequently in adulthood (see Khandaker et al. JAMA Psychiatry 2014; Metcalf et al. Brain, Behaviour and Immunity 2017; Khandaker et al. Psychological Medicine 2017). These findings suggest low-grade systemic inflammation is unlikely to be simply a consequence of the illness; it could well be a cause of depression and schizophrenia.

Recently, we have shown that anti-inflammatory drugs improve depressive symptoms in patients with chronic inflammatory illness such as rheumatoid arthritis (see Kappelmann et al. Molecular Psychiatry 2016). However, studies of anti-inflammatory drugs in patients with depression who do not have a chronic inflammatory physical illness are rare. Such studies are required to understand whether anti-inflammatory drugs could treat depression, and to understand the mechanism of their antidepressant action.

The Insight Study is a proof-of-concept, randomised, double blind, placebo controlled study led by Dr Khandaker at the University of Cambridge. The primary aim of this study is to investigate the effects of reducing inflammation by inhibiting the IL-6 pathway in depressed patients who have not sufficiently improved on antidepressants and have evidence of low-grade inflammation. We will use a novel anti-inflammatory drug licensed for treatment of rheumatoid arthritis to inhibit the IL-6 pathway (tocilizumab). We are interested to find out whether reducing inflammation can help reduce certain symptoms of depression, and mechanisms behind such an effect. The secondary aim of this study is to examine how depressed patients with low-grade systemic inflammation differ from those who do not have low-grade systemic inflammation.

The Insight Study is funded by the Wellcome Trust.

Participate in the Insight study

More information on how to participate in the Insight study will be added soon.

Meanwhile, please direct any informal queries about this study to the InPsych group.

Contact Us

We are happy to hear from prospective group members, research collaborators, participants, media, patients and others. Email:

Our address

Department of Psychiatry
University of Cambridge
Herchel Smith Building for Brain and Mind Sciences
Cambridge Biomedical Campus
Cambridge, CB2 0SZ, UK

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