Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial

J C Zwiep; P M Bet; D Rhebergen; M T Nurmohamed; C H Vinkers; B W J H Penninx; Y Milaneschi; F Lamers

doi:10.1016/j.bbih.2022.100585

Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial

Brain Behav Immun Health. 2022 Dec 30:27:100585. doi: 10.1016/j.bbih.2022.100585. eCollection 2023 Feb.

Authors

J C Zwiep^{1

2}, P M Bet³, D Rhebergen^{1

2

4}, M T Nurmohamed⁵, C H Vinkers^{1

2

6

7

8}, B W J H Penninx^{1

2

6}, Y Milaneschi^{1

2

6}, F Lamers^{1

2}

Affiliations

¹ Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1117, 1118, 1081 HV, Amsterdam, the Netherlands.
² Amsterdam Public Health, Mental Health Program, Amsterdam, the Netherlands.
³ Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1117, 1118, 1081 HV, Amsterdam, the Netherlands.
⁴ GGZ Centraal Mental Health Care, Department of Research, Amersfoort, the Netherlands.
⁵ Department of Rheumatology, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1117, 1118, 1081 HV, Amsterdam, the Netherlands.
⁶ Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, the Netherlands.
⁷ Department of Anatomy & Neurosciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1118, 1081 HV, Amsterdam, the Netherlands.
⁸ GGZ InGeest Mental Health Care, 1081 HJ, Amsterdam, the Netherlands.

Abstract

Introduction: As the role of (neuro)inflammation in depression pathophysiology is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs have shown beneficial results, but not consistently across all studies. Inconsistencies may be due to depression biological and clinical heterogeneity. Immuno-Metabolic Depression (IMD) has been put forward as a form of depression characterized by the clustering of low-grade inflammation, metabolic dysregulations and atypical, energy-related symptoms (overeating, weight gain, hypersomnia, fatigue and leaden paralysis). IMD features are present in ∼30% of patients with Major Depressive Disorder (MDD). By selecting these specific patients, directly targeting inflammation may reduce depressive symptoms.

Methods: and analysis INFLAMED is a double-blind randomized controlled trial. 140 MDD patients with IMD characteristics (MDD with Inventory of Depressive Symptomatology (IDS) ≥ 26, IDS atypical, energy related symptoms ≥6, C-Reactive Protein (CRP) > 1 mg/L) will receive either 400 mg celecoxib per day or matching placebo for a period of 12 weeks. Biological, physical and interview data will be collected after 2, 6 and 12 weeks of starting the intervention. Questionnaires will be sent out bi-weekly during the study period. The main study outcome is the IDS (30-item self-report) total score during 12-week follow-up. Secondary study outcomes include response, remission, adverse side effects, symptom profiles (atypical, energy-related symptoms), fatigue, food craving, sleep, anxiety symptoms, functioning, pain, and optionally, microbiome composition. Explorative analyses will be performed on the role of CRP, IL-6, TNF-α, cholesterol, triglycerides, glucose, BMI, waist and hip circumference.

Ethics and dissemination: This protocol has been approved by the Medical Ethics Review Board of the Amsterdam UMC, location VUmc (2022.0015) on 2-6-2022, as well as by the competent authority in The Netherlands: CCMO, on 3-8-2022.

Registration details: Trail registration numbers NCT05415397, EudraCT 2021-003850-21.

Keywords: Anti-inflammatory medication; Celecoxib; Inflammation; Major depressive disorder; Metabolism; Randomized controlled trial; Treatment.

Associated data

ClinicalTrials.gov/NCT05415397