Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression
Condition: Depression; Hypertension
MeSH terms: Hypertension; Depression; Depressive Disorder
Intervention: Sertraline; Candesartan
Intervention description: 50mg - 200mg daily; 4mg - 32mg daily
Intervention MeSH terms: Candesartan; Candesartan cilexetil; Sertraline
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Depression; Depressive Disorder; Geriatrics; Hypertension

Summary:

      This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and
      cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the
      relationship between vascular disease and depression in older adults. The long-term objective
      of this line of research is to: A) determine the relationship between vascular reactivity,
      cerebral hypoperfusion and the persistence of late-life depression and B) determine if
      improving cerebral perfusion with angiotensin receptor blockers (ARBs) improves depression
      outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 60 years or older

          2. Diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic
             features by Diagnostic and Statistical Manual IV Text Revision (DSMIV-TR) criteria

          3. Presence of hypertension (defined as systolic > 140 or diastolic > 90 or currently
             receiving antihypertensive therapy)

          4. Minimum depression severity of ≥ 15 on the Montgomery-Asberg Depression Rating Scale
             (MADRS)

          5. Cognitively intact or with mild cognitive deficits, with a minimum score ≥ 23 on the
             Montreal Cognitive Assessment (MoCA).

        Exclusion Criteria:

          1. Other psychiatric Axis I disorders

          2. Acute suicidality

          3. Electroconvulsive therapy in the last 6 months

          4. Primary neurological disorder, including dementia and stroke

          5. Significant cardiovascular disease, specifically diagnosis of congestive heart
             failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical
             aortic or mitral stenosis

          6. Myocardial infarction or open-heart surgery in last 6 weeks

          7. Serum creatinine ≥ 265 micromol /L

          8. Serum potassium ≥ 5.5 mmol/L

          9. MRI contraindications

         10. Known allergy to sertraline or candesartan specifically or known allergy to other
             SSRIs or ARBs.

         11. History of prolonged (> 3 weeks) or self-described severe discontinuation syndrome in
             the past after stopping an antidepressant.

         12. Current use of an angiotensin receptor blocker

         13. Current or planned psychotherapy

         14. Need for continuous oxygen use or any medical disorder where the hypercapnia challenge
             would be contraindicated or put the subject at increased risk. This would include
             acute respiratory disease, chronic angina, or other unstable cardiac conditions.