Frontal Hypoperfusion Effects on Antidepressant Outcomes in Late-Life Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: Sertraline
Intervention description: 50-200mg daily
Intervention MeSH terms: Sertraline
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Depression; Antidepressants; Elderly; Geriatrics

Summary:

      The long-term goal of this line of research is to determine if decreased vascular reactivity
      and frontal hypoperfusion is associated with poor response antidepressants. Such perfusion
      deficits could contribute to antidepressant nonresponse as they would hinder improvements in
      dorsal system metabolism seen with antidepressant treatment. The objective of the current
      proposal is to determine if decreased vascular reactivity and frontal hypoperfusion in
      depressed elders predicts and persists with antidepressant nonremission. The investigators
      will pursue the primary aim testing the hypothesis that decreased reactivity and
      hypoperfusion, specifically in the dorsolateral prefrontal cortex and dorsal anterior
      cingulate cortex, predict antidepressant nonremission. The investigators will enroll 40
      depressed elders who will complete clinical, cognitive, and MRI assessments before and after
      a 12-week open-label antidepressant trial of sertraline.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 60 years or older.

          2. Current diagnosis of major depressive disorder (DSM-IV-TR), single episode, recurrent
             or chronic, without psychotic features, as detected by MINI and clinical exam.

          3. Minimum MADRS score ≥ 15.

          4. Mini-Mental State Exam ≥ 22.

          5. Ability to read and write English.

        Exclusion Criteria:

          1. Current or past diagnoses of other Axis I psychiatric disorders, including panic
             disorder and substance dependence.

          2. Any use of illicit substances (such as marijuana or cocaine) or abuse of prescription
             medications (such as benzodiazepines or opiates) within the last three months.

          3. Presence of acute suicidality

          4. Current or past psychosis

          5. Known primary neurological disorder, including dementia, brain tumors, epilepsy,
             Parkinson's disease, or demyelinating diseases

          6. Chronic untreated medical disorders (including but not limited to hypertension,
             hyperlipidemia, fibromyalgia, hypothyroidism, or any other disorder) where treatment
             is warranted

          7. 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
             active respiratory disease, chronic angina or other unstable cardiac conditions.

          8. Any physical or intellectual disability affecting completion of assessments

          9. MRI contraindications

         10. Electroconvulsive therapy in last 6 months

         11. Use of fluoxetine in the last 6 weeks. Occasional use of benzodiazepines or
             non-benzodiazepine sedatives (such as zolpidem, eszopiclone, or zaleplon) during the
             last month is allowable.

         12. Known allergy or hypersensitivity to sertraline

         13. A failed therapeutic trial of sertraline in the current depressive episode (defined as
             at least 6 weeks of treatment at a daily dose of 100mg or higher)

         14. Current or planned psychotherapy