A Phase 3 interventional study of Celecoxib 400mg and Placebo in Depressive Disorder, Major and Inflammation, sponsored by Amsterdam UMC, location VUmc. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Amsterdam UMC, location VUmc · Phase 3, Interventional, and Treatment
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.
Rationale: 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. The investigators of the present study 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. In this study IMD will be applied as a tool to personalize treatment, by matching depressed subjects with IMD with a targeted anti-inflammatory add-on treatment. The underlying hypothesis is 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.
Objective: Among patients under treatment for depression, 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.
Study design:12-week double-blind placebo-controlled randomized clinical trial Study population: 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.
Intervention: celecoxib add-on (400 mg/d) vs placebo Main study parameters/endpoints: Primary outcome parameter is the difference in trajectories of depression symptoms, as measured with the 30-item Inventory of Depressive Symptomatology - self-report during follow-up. Secondary outcome parameters include amongst others, response on the IDS, remission, anxiety, fatigue, food craving, sleep and adverse side events.
2,740 studies on the registry are indexed under Depressive Disorder, Major; 558 are open to participants now.
This study's enrollment of 94 is above the median of 80 across 2,282 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Amsterdam UMC, location VUmc is the lead sponsor of 302 studies on the registry; 84 are open to participants now.
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Exclusion Criteria:
Celecoxib 400 mg/day, 2 capsules (200 mg) daily, 12 weeks
Drug: Celecoxib 400mg
Placebo, 2 capsules daily, 12 weeks
Drug: Placebo
Celecoxib add-on (400mg daily) add-on to treatment as usual (standard antidepressant treatment)
Also known as: Celecoxib, ATC M01AH01
Placebo add-on to treatment as usual (standard antidepressant treatment)
Depressive symptoms severity
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
Time frame: 12 weeks
Number of participants achieving Response
Response is defined as 50% reduction in depressive symptoms severity measured with Inventory of Depressive Symptomatology - Self Report (IDS-SR; score ranging from 0 to 84, higher scores indicate higher severity of depressive symptoms)
Time frame: 12 weeks
Number of participants achieving Remission
Remission is defined as absence of DSM-5 Major Depressive Disorder (MDD), identified using the Mini International Neuropsychiatric Interview - Simplified (MINI-S voor DSM-5 Nederlandse versie 2019)
Time frame: 12 weeks
Symptom profile: atypical, energy-related depressive symptoms (AES)
AES measured with 5 items (N 4, 12, 14, 20, 30) of the Inventory of Depressive Symptomatology - Self Report (IDS-SR). AES score ranging from 0 to 15, higher scores indicate higher severity of depressive symptoms.
Time frame: 12 weeks
Fatigue
Fatigue measured by the Checklist Individuele Spankracht (CIS), which assess fatigue in 4 subscales: subjective experience of fatigue, reduction in motivation, reduction in activity and reduction in concentration. In each domain, higher scores indicate higher fatigue
Time frame: 12 weeks
Food craving
Food craving measured with General Food Craving Questionnaire Trait (G-FCQ-T; score ranging from 21 to 126, higher scores indicate more intense food craving)
Time frame: 12 weeks
Daytime sleepiness
Daytime sleepiness measured with the Epsworth Sleepiness Scale (ESS; score ranging from 0 to 24, higher scores indicates higher propensity to daytime sleepiness)
Time frame: 12 weeks
Night-time sleep
Sleep Duration measured with items 1,2,3 and 4 (self reports of bed time, asleep time, wake-time, sleep duration) of the Pittsburgh Sleep Quality Index (PSQI)
Time frame: 12 weeks
Anxiety symptoms
Anxiety symptoms measured with General Anxiety Disorder-7 (GAD-7, score ranging from 0 to 21, higher scores indicate higher anxiety)
Time frame: 12 weeks
Functionality
General functioning and disability measured with the WHO Disability Schedule (WHODAS, score ranging from 12 to 60, higher scores indicate more disability)
Time frame: 12 weeks
Pain severity
Pain measured by numeric rating scale (score ranging from 0 to 10, higher scores indicate higher pain)
Time frame: 12 weeks
Therapy compliance
Pill count
Time frame: 12 weeks
Inflammatory and metabolic blood markers
CRP, IL-6, TNF-α, cholesterol, triglycerides, glucose
Time frame: 12 weeks
Side effects
Side effects measured with the list applied in the PREDDICT RCT and theThe Antidepressant Side-Effect Checklist (ASEC-21)
Time frame: 12 weeks
Plan to share: Yes — Individual data collected during the study of participants explicitly agreeing on this possibility trough written informed consent; data will be de-identified
Supporting information: Study protocol
This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Amsterdam UMC, location VUmc