Stress and Inflammation in Late-Life Depression
Condition: Depression; Inflammation
MeSH terms: Inflammation; Depression; Depressive Disorder
Intervention: Escitalopram + Celecoxib; Escitalopram + Placebo
Intervention description: Participants will receive celecoxib in addition to escitalopram; Participants will receive a placebo in addition to escitalopram.
Intervention MeSH terms: Celecoxib; Dexetimide; Citalopram; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 119.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Depression; Geriatric; Inflammation

Summary:

      Over 18% of Americans aged 65 years and older have depression. Recent evidence suggests that
      there is a link between depression and inflammatory disease. This study investigates the
      relationship between inflammation in the brain and depression. Comparing biological and
      psychological differences in depressed and non-depressed people allows researchers to find
      better ways to treat and prevent depression. All participants will have: neuropsychological
      tests, an EKG, a spinal tap, a blood draw, and, if depressed, given either an antidepressant
      coupled with an anti-inflammatory medication or an anti-depressant coupled with a placebo for
      six weeks. The investigators are trying to correlate brain function with depression levels
      and biomarkers from the blood and spinal fluid.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18-80, male or female, any race;

          2. Absence of clinical dementia

          3. English speaking

          4. Blood pressure not exceeding 150/90 mmHg, treated or untreated

          5. Weight greater than 110 lbs

          6. Normal result on liver-function test

          7. No history of ulcer disease or GI bleeding

          8. No renal insufficiency

        Additional Inclusion Criteria for Depressed Participants:

          1. DSM-IV criteria for Major Depressive Disorder

          2. HAM-D greater than 18

        Exclusion Criteria:

          1. Known history of relevant severe drug allergy or hypersensitivity (e.g. to Citalopram
             or Escitalopram, and/or to celecoxib, aspirin, or other NSAIDs only for Phase 2; known
             demonstration of allergic-type reactions to sulfonamides);

          2. Does not speak English;

          3. Cannot give informed consent;

          4. MRI contraindications (e.g., foreign metallic implants, pacemaker);

          5. Known primary neurological disorders, such as Parkinson's disease, Alzheimer's
             disease, traumatic brain injury, cognitive impairment or dementia,

          6. Known severe inflammatory disease such as systemic lupus erythematosis, known
             autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis; Screen + for
             RF, ANA, HIV, Hepatitis B or C.

          7. Clinical Dementia Rating Scale score greater than 0;

          8. Diagnosis of a chronic psychiatric illness other than MDD at the discretion of the
             study doctor;

          9. Significant handicaps (e.g. uncorrected hearing or visual impairment, mental
             retardation) that would interfere with testing;

         10. Bleeding diathesis;

         11. Severe Medical problem, which in the opinion of the investigator would pose a safety
             risk to the subject;

         12. Clinically significant cardiovascular disease that will be assessed on a case-by-case
             basis. Clinically significant cardiovascular disease usually includes one or more of
             the following: cardiac surgery or myocardial infarction within the last 4 weeks;
             unstable angina; acute decompensated congestive heart failure or class IV heart
             failure; current significant cardiac arrhythmia or conduction disturbance,
             particularly those resulting in ventricular fibrillation, or causing syncope or near
             syncope; uncontrolled high blood pressure; QTc greater than 450msec (by history for
             subjects with cardiac disease); documented prior stroke;

         13. Clinically significant abnormalities on EKG. Primary AV block or Right bundle branch
             block are not necessarily exclusionary;

         14. Current diagnosis of cancer

         15. Current diagnosis of HIV, active Hepatitis B and/or Hepatitis C

         16. Use of an Investigational medicine within the past 30 days;

         17. Use of Coumadin, Warfarin within the past 2 months;

         18. Current treatment with psychotropic drugs or drugs that affect the CNS such as
             beta-blockers, mood stabilizers, antipsychotics, steroids or non-steroidal
             anti-inflammatory medications or other antidepressants. No subjects will be included
             in the study unless they have been off all psychotropics for at least 3 weeks, except
             in the case of fluoxetine, where 5 weeks off treatment will be required;

         19. Current alcohol or substance abuse disorder, schizophrenia or other psychotic
             disorder, bipolar disorder, or current OCD;

         20. Abnormal liver-function test

         21. History of ulcer disease, Chron's disease, GI bleeding or anemia

         22. Weight less than 110 lbs

         23. Renal insufficiency

         24. Any other factor that in the investigator's judgment may affect patient safety or
             compliance (e.g. distance greater than 100 miles from this facility);

        Additional Exclusion Criteria for Depressed Subjects:

        1) Active suicidality or current suicidal risk as determined by the investigator