Precision psychiatry: Anti-inflammatory medication in Immuno-metabolic depression (INFLAMED)

Depression is a major driver of disability and related health-care costs. Available treatment options are far from optimal, with only ~60% response. Developing effective treatments requires new treatment targets to depression pathophysiology. As the role of (neuro)inflammation in depression is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs such as celecoxib has shown encouraging preliminary results.

However, inflammation is not present in all depressed patients. Depression is heterogeneous: patients express diverse and sometimes opposing symptoms and biological profiles. We recently introduced the concept of ImmunoMetabolic Depression (IMD), characterized by the clustering of inflammatory/metabolic dysregulations and atypical, energy-related symptoms (hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis), and present in 30% of cases. Converging evidence suggests that in this subgroup of depression cases, inflammation may exert a crucial pathobiological mechanism, representing therefore an actionable therapeutic target. We will apply IMD as a tool to personalize treatment, by matching depressed subjects with IMD with a targeted anti-inflammatory add-on treatment. We expect that this personalized intervention in subjects with IMD, through a reduction of inflammation, lowers depressive symptoms and associated physical fatigue, while increasing functioning compared to placebo.

Among patients under treatment for depression, we will select 140 persons with IMD. In this specific group of patients, we will test whether celecoxib add-on (400 mg/d) is more effective than placebo in the treatment of depression through a 12-week double-blind, randomized (1:1), placebo-controlled trial.

Study design & population
12-week double-blind placebo-controlled randomized clinical trial in 140 persons with major depressive disorder (DMS-5)with atypical, energy-related symptoms (≥6 on IDS atypical, energy-related symptoms) AND low-grade inflammation (CRP>1mg/L)(e.g. ImmunoMetabolic Depression), and under treatment with SSRI or SNRIs.

This study is funded by the The Brain Foundation Netherlands (Hersenstichting)


Joël Zwiep, MSc