Abstract
Aims
Pharmacotherapy for depression is predicated on monoamine neurotransmitters, but other mechanisms are likely to be involved. Observational studies indicate potentially causal role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in pathogenesis of depression, but interventional studies based on depressed patients have not yet been conducted. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 receptor signalling and is licensed in the UK for treatment of rheumatoid arthritis. The Insight study aims to test whether IL-6 contributes to pathogenesis of depression and to determine its potential as a treatment target.
Methods
Proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial involving 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression and evidence of low-grade inflammation (defined as serum high-sensitivity C-reactive protein level ≥3 mg/L) randomised to a single intravenous infusion of either tocilizumab or normal saline. Mood, cognition and blood-based immunological measures assessed at baseline and 7, 14 and 28 days after infusion. The primary outcome is depression somatic symptoms score approximately 14 days post-infusion.
Results
To date, 24 patients have been recruited and treated with tocilizumab/placebo; mean age 40.32 years (SD=12.37), 20 (83.33%) females, 21 (87.50%) white ethnicity. Based on data thus far, intravenous tocilizumab appears to be well tolerated by depressed patients. No severe adverse reactions were noted. Mild, brief, self-limiting influenza-like symptoms were noted for 3 participants.
Conclusions
Based on the data collected to date, intravenous tocilizumab treatment is feasible, well-tolerated and accepted by depressed patients. Side effect incidence is low.
Pharmacotherapy for depression is predicated on monoamine neurotransmitters, but other mechanisms are likely to be involved. Observational studies indicate potentially causal role for interleukin 6 (IL-6), a pro-inflammatory cytokine, in pathogenesis of depression, but interventional studies based on depressed patients have not yet been conducted. Tocilizumab is a humanised monoclonal antibody that inhibits IL-6 receptor signalling and is licensed in the UK for treatment of rheumatoid arthritis. The Insight study aims to test whether IL-6 contributes to pathogenesis of depression and to determine its potential as a treatment target.
Methods
Proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial involving 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression and evidence of low-grade inflammation (defined as serum high-sensitivity C-reactive protein level ≥3 mg/L) randomised to a single intravenous infusion of either tocilizumab or normal saline. Mood, cognition and blood-based immunological measures assessed at baseline and 7, 14 and 28 days after infusion. The primary outcome is depression somatic symptoms score approximately 14 days post-infusion.
Results
To date, 24 patients have been recruited and treated with tocilizumab/placebo; mean age 40.32 years (SD=12.37), 20 (83.33%) females, 21 (87.50%) white ethnicity. Based on data thus far, intravenous tocilizumab appears to be well tolerated by depressed patients. No severe adverse reactions were noted. Mild, brief, self-limiting influenza-like symptoms were noted for 3 participants.
Conclusions
Based on the data collected to date, intravenous tocilizumab treatment is feasible, well-tolerated and accepted by depressed patients. Side effect incidence is low.
| Original language | English |
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| DOIs | |
| Publication status | Published - 20 Dec 2024 |
| Event | Federation of European Neuroscience Societies 2020 Virtual Forum - Duration: 11 Jul 2020 → 15 Jul 2020 |
Conference
| Conference | Federation of European Neuroscience Societies 2020 Virtual Forum |
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| Abbreviated title | FENS 2020 Virtual Forum |
| Period | 11/07/20 → 15/07/20 |