INSTA-MD: INflammation-based Stratification for immune-Targeted Augmentation in Major Depressive disorder

Prior treatment

• Primary diagnosis of bipolar disorder, psychotic spectrum disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or alcohol and/or substance use dependence according to DSM-5 (< 4 weeks before screening, excl. nicotine and caffeine)
• Received ECT < 2 months prior to screening
• Blood donation in 30 days prior to screening
• Concomitant penicillin or anticoagulant therapy
• Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.)
• Use of (Vitamin K) anticoagulant therapy
• Having received >14 days of tetracycline or NSAID within the previous 2 months, or having a history of sensitivity or intolerance to this classes of drugs

Other illness

• Serology positive for hep-B surface antigen, hep-C antibodies or HIV antibodies
• History of peptic ulcer disease or gastrointestinal (GI) bleeding
• Having an acute infection or having an inflammatory bowel disorder.
• Current severe cardiovascular disease (e.g. congestive heart failure (NYHA-class II–IV), ischemic or thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery))
• Chronic severe hypertension (systolic BP > 170 mmHg)

Lab values

• Having an acute infection in the last two weeks, neutrophilia or leukocytosis at screening (i.e. neutrophils ≥ 10 x10^9 /L or white blood cell count ≥ 12 x10^9 /L)

Other

• The current episode of depression has failed to remit after four trials of antidepressant treatment.
• Pregnancy or breastfeeding
• Being diagnosed with Familial Adenomatous Polyposis (FAP).
• Currently enrolled in an intervention study

• 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 pregnancy tests.
• A score of 14 or higher on the Hamilton Depression Rating scale (HDRS-17)