Stony Brook Medicine Anti-Inflammatory Trial

This is an experimental study designed to measure the effect of celecoxib or minocycline on depressive symptoms in unipolar and bipolar depression. Participants will be equally randomized to either celecoxib or minocycline. All participants will complete a battery of clinical and psychological assessments prior to treatment assignment, and again after treatment completion, to assess any changes or improvements in depression.

Inclusion Criteria: * Current consent form signed * Capacity to give informed consent * Age range 18-65 (inclusive) * Diagnosis of MDD or bipolar depression and currently in a major depressive episode * Score of at least 29 on the MADRS (at least moderate depression) Exclusion Criteria: * Hypersensitivity to celecoxib, minocycline, tetracyclines, sulfonamides, aspirin, other NSAIDs, or any component of the formulation; previous asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs * History of myocardial infarction or current cardiac condition * Heptic impairment, heart failure, severe renal impairment, recent GI bleed, history of peptic ulcer disease, anemia or any other contraindication for celecoxib or minocycline * Poor CYP2C9 metabolizer * Currently taking medications that interact with celecoxib (digoxin, antihypertensives, diuretics, anticoagulant or anti-platelet treatment, including aspirin), or minocycline (isotretinoin, ergot alkaloids) without providing physicians approval * Use of herbs, drugs, or medications with anti-inflammatory or immunomodulatory properties (within 5 half-lives of starting celecoxib or minocycline treatment) * Unlikely to tolerate medication washout or the medication-free period following washout. * Participant considered at significant risk for suicide. * Electroconvulsive therapy (ECT) within 1 month * High potential for excessive drug/alcohol use during the treatment period (excluding nicotine or cannabis) * Significant active physical illness or neurological deficit that may affect brain functioning. * If participant is currently pregnant, breastfeeding, or planning to conceive during the course of study participation. * Need for medications that control mania.