Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression

• Status: Terminated
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University
• Treatments: Candesartan; Candesartan cilexetil; Sertraline

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.