NCT05415397: INFLAMED

Precision Psychiatry: Anti-inflammatory Medication in Immuno-metabolic Depression

Active, enrolled Phase 3 Last updated 2 April 2026

What this trial tests

Phase 3 trial testing Celecoxib 400mg in Depressive Disorder, Major in 140 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

28 September 2022

Primary endpoint
1 July 2026

1 July 2026

Quick facts

Lead sponsor	Amsterdam UMC, location VUmc
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	140
Start date	28 September 2022
Primary completion	1 July 2026
Estimated completion	1 July 2026
Sites	1 location across Netherlands

Drugs / interventions tested

• Celecoxib 400mg — full drug profile →
• Placebo

Conditions studied

• Depressive Disorder, Major — all drugs for Depressive Disorder, Major →
• Inflammation — all drugs for Inflammation →

Sponsor

Amsterdam UMC, location VUmc — full company profile →

Who can join

Adults 18 to 65, any sex, with Depressive Disorder, Major or Inflammation. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Depressive symptoms severity
  Time frame: 12 weeks
  Depressive symptoms severity measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR; score ranging from 0 to 84, higher scores indicate higher severity of depressive symptoms). Trajectories of depressive symptoms will be modeled via mixed models including bi-weekly assessments

Sponsor's own description

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. The investigators of the present trial 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 approximately 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. In this trial IMD will be applied as a tool to personalize treatment, by matching depressed subjects with IMD with a targeted anti-inflammatory add-on treatment.

In this study, 140 persons with IMD will be selected. In this specific group of patients, the investigators 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. By selecting specifically depressed patients with IMD, the proposed treatment selectively targets key inflammatory pathophysiological pathways to enhance clinical outcome for depression. This personalized approach is expected to lead to large health gains for a sizable proportion of patients. The main hypothesis is that the group of patients with IMD receiving TAU + celecoxib, as compared to the TAU + placebo, will show a better symptom course over the 12-week follow-up.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial.
   Zwiep JC, Bet PM, Rhebergen D, Nurmohamed MT, et al · · 2023 · cited 15× · PMID 36655056 · DOI 10.1016/j.bbih.2022.100585
2. Botulinum Toxin: An Unconventional Tool for the Treatment of Depression?
   Gambini M, Gurrieri R, Russomanno G, Cecchini G, et al · · 2025 · PMID 41008331 · DOI 10.3390/brainsci15090971