JAK Signaling in Depression

Exclusion Criteria24

• history or evidence (clinical and laboratory) of an autoimmune disorder
• history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection;
• history of any type of cancer requiring treatment with more than minor surgery;
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
• significant hematological abnormalities at screening (ANC < 1500, Hgb<10, platelet< 100,000)
• history of progressive multifocal leukoencephalopathy,
• history of deep venous thrombosis,
• history of cardiovascular disease (coronary artery disease, congestive heart failure, stroke - controlled hypertension is OK),
• major surgery within 8 weeks prior to screening or will require major surgery during the study,
• current or recent (<4 weeks prior to randomization) viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection,
• symptomatic herpes zoster infection at or within 12 weeks of randomization,
• history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement),
• cirrhosis of the liver from any cause,
• any of the following specific abnormalities on screening laboratory tests: ALT or AST >2 x upper limits of normal (ULN), alkaline phosphatase (ALP) ≥2 x ULN, total bilirubin ≥1.5 x ULN (with the exception of patients on atazanavir, who must have total bilirubin <2 x ULN),
• chronic kidney disease with eGFR <60 mL/min/1.73 m2,
• history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by standardized clinician interview);
• active suicidal plan as determined by a score >3 on item #3 on the HAM-D; g. an active eating disorder (except for patients with binge eating disorder in whom binging is clearly associated with worsening of mood symptoms);
• history of a cognitive disorder or traumatic head injury involving loss of consciousness;
• pregnancy or lactation,
• use of gender affirming hormone therapy;
• chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), immunosuppressive (e.g., biologics), glucocorticoid containing medications or minocycline within 6 months, or non-prescription supplements with known or suspected anti-inflammatory properties (e.g. fish oil supplements) within 2 weeks of baseline, or at any time during the study;
• any contraindication for MRI scanning;
• failure of more than 2 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime; and
• BMI >45 (to exclude severe obesity) or at the PI's discretion based on the patient's ability to fit comfortably in the MRI scanner.