Using anti-inflammatory drugs to treat major depressive disorder

INflammation-based Stratification for Immune-Targeted Augmentation in Major Depressive

This study is testing whether two anti-inflammatory medications can help people with major depressive disorder who haven't found relief with regular antidepressants.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Universiteit Antwerpen (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 3 sites (Duffel, Antwerpen and 2 other locations)
• Trial ID: NCT05644301 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of two established anti-inflammatory medications, minocycline and celecoxib, as adjunct therapies for patients with major depressive disorder who have not responded to standard antidepressant treatments. The study employs a randomized, double-blind, placebo-controlled design to assess the efficacy of these drugs in a specific subgroup of patients characterized by inflammation-related depression. By stratifying patients based on their inflammatory status, the trial aims to identify which individuals may benefit most from these treatments, ultimately paving the way for personalized approaches in managing depression.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with a diagnosis of major depressive disorder who have not responded to current antidepressant therapy.

Not a fit: Patients with primary diagnoses of bipolar disorder, psychotic spectrum disorders, or obsessive-compulsive disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide new treatment options for patients with treatment-resistant major depressive disorder.

How similar studies have performed: Previous studies have shown promise in using anti-inflammatory drugs for depression, but this specific approach of stratifying by inflammatory status is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Male or female, 18-65 years inclusive.
* Able and willing to give informed consent and take oral medication.
* Physically healthy.
* Diagnosis of Major Depressive Disorder by DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI).
* The current episode of depression has failed to remit to the current antidepressant treatment at the adequate dose (as defined in the Maudsley Prescribing guidelines). Relapse while taking an antidepressant is also considered a treatment failure.
* Tolerant to the current antidepressant and having no planned changes in their current therapy for the duration of the study.
* Stable on current treatment for a minimum of 4 weeks (6 weeks for fluoxetine) prior to baseline.
* If female and of childbearing age, willing to use adequate contraceptive precautions and willing to take a pregnancy test at baseline.

Exclusion Criteria:

* Primary diagnosis of a bipolar disorder, psychotic spectrum disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or alcohol and/or substance use disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (\< 4 weeks before screening, excl. nicotine and caffeine).
* Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.).
* History of peptic ulcer disease or gastrointestinal (GI) bleeding.
* Having an acute infection or inflammatory bowel disorder.
* Current severe cardiovascular disease, congestive heart failure (NYHA-class II-IV), ischemic or thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery),
* Liver impairment (alanine aminotransferase \> 2x upper limit, serum albumin \< 25 g/l or Child-Pugh Score ≥ 10)
* Renal impairment (creatinine clearance \< 30 mL/min).
* Having received \>14 days of tetracycline or non-steroidal anti-inflammatory medication within the previous 2 months, or having a history of sensitivity or intolerance to these classes of drugs.
* Chronic severe hypertension (systolic BP \> 170 mmHg).
* Serology positive for hepatitis-B surface antigen, hepatitis-C antibodies or HIV antibodies.
* Received electroconvulsive therapy \< 2 months prior to screening.
* Blood donation in 30 days prior to screening.
* Pregnancy or breastfeeding.
* Currently enrolled in an intervention study.

Where this trial is running

Duffel, Antwerpen and 2 other locations

• UPC Duffel — Duffel, Antwerpen, Belgium (Recruiting)
• UZ Brussel — Brussels, Belgium (Recruiting)
• Katholiek Universiteit Leuven Campus Kortenberg — Leuven, Belgium (Recruiting)

Study contacts

• Principal investigator: Manuel Morrens, MD PhD — Professor
• Study coordinator: Jonas Janssens, MD

Conditions Major Depressive Disorder; Inflammation; Immunopsychiatry; Celecoxib; Minocyclin; Randomised Controlled Clinical Trial