Abstract
In 2018, 6% of people over the age of 15 had a depressive disorder in the Flemish Region (Statistiek Vlaanderen). In 2019, this was 36 million people per year for Europe, good for 92 billion euros in annual costs (WHO Global Burden of Disease 2019). The WHO estimates that depression will be one of the leading causes of disease burden by 2030. Depression, however, is very heterogeneous, with an estimate of 33-40% responding poorly or not at all to gold standard treatment. Innovation in the field of treatment could therefore have a major impact for this subgroup.
This project aims to repurpose two established anti-inflammatory compounds as adjuvant therapy for immune-mediated depression, in line with state-of-the-art research of the last 10 years. Immune-mediated depression represents a subtype which accounts for approximately 30% of depressive disorders (Osimo et al., 2019). Patients with this immunosubtype are more likely to have a higher severity of depression, a lower quality of life and more somatic symptoms (Foley et al., 2021). Furthermore, it is accompanied by a high incidence of treatment resistance (Carvalho et al., 2013). While their mechanisms of action completely differ from those of existing antidepressant treatment options, immunomodulatory drugs celecoxib and minocycline have proven their merit as add-on treatment in depressive episodes. They have been on the Belgian market for years and come with a known pharmacological and safety profile. Patient stratification at baseline based on inflammatory status will reveal which inflammatory subpopulation benefits most from each of the two investigated anti-inflammatory compounds. Additionally, our distinctive study design allows head-to-head comparison of both add-on therapies and will as such provide the last stepping stones towards clinical implementation of individualised treatment strategies in depression.
The novelty and clinical relevance of this project reside in (1) the direct comparison of each compound separately as well as (2) the selection of patients who may benefit from anti-inflammatory treatment via stratification based on baseline inflammatory levels. Hence, this project will tackle a knowledge gap vital for the development of clinical practice guidelines. The addition of this treatment option to the psychiatric arsenal and the inflammation-based stratification prior, opens the way to a pragmatic strategy in the form of personalised medicine in biological psychiatry. This could support and optimise the choice of psychiatric treatment, thus limiting exposure to ineffective treatments and shortening the length of hospital stay. As a result, this repurposing strategy will significantly reduce the associated health care costs, without the additional costs associated with bringing new compounds to market.
Objectives
Validate the efficacy of immune-targeted augmentation with minocycline or celecoxib in a Flemish cohort of patients with MDD who failed to remit with one or two trials of antidepressant treatment;
Compare the respective acceptability, treatment response and remission rates of minocycline and celecoxib as adjunctive therapy;
Compare the efficacy of both compounds as adjunctive therapy in an immune-mediated subtype of MDD versus an unstratified patient sample;
Evaluate the use of hsCRP as a predictor for treatment response to minocycline and celecoxib.
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