L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
Condition: Major Depressive Disorder; Dysthymia; Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Dysthymic Disorder
Intervention: L-DOPA; Placebo Oral Tablet
Intervention description: We will be using generic sinemet 25/100 tablets in this study.; 25/100 placebo tablets
Intervention MeSH terms: Levodopa; Carbidopa; Carbidopa, levodopa drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double Blind
Enrollment: 51.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Depressive symptoms; Cognitive problems; Antidepressant non-response; Dopamine system; Older Adults; Motor slowing

Summary:

      Individuals with Late Life Depression (LLD) often have cognitive problems, particularly
      problems with memory, attention, and problem solving, all of which contribute to
      antidepressant non-response. Our group and others have shown that decreased thinking speed is
      the central cause of functional problems in patients with LLD. Similarly, decreased walking
      speed is associated with depression and carries additional risk for falls, hospitalization,
      and death. Available evidence suggests that declining functionality in the brain's dopamine
      system contributes to age-related cognitive and motor slowing. The central hypothesis of this
      study is that by enhancing dopamine functioning in the brain and improving cognitive and
      motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms
      in older adults.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged 60 years and older

          2. DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise
             Specified

          3. Hamilton Rating Scale for Depression (HRSD) > 15

          4. Decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on
             Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed
             (defined as average walking speed over 15' course < 1m/s)

          5. Willing to and capable of providing informed consent and complying with study
             procedures

          6. Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g.,
             antidepressant medication or psychotherapy) have been discussed and the individual
             agrees to be involved in an experimental treatment.

        Exclusion Criteria:

          1. Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the
             past 12 months.

          2. History of or current psychosis, psychotic disorder, mania, or bipolar disorder

          3. Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease
             (PD)

          4. Mini Mental Status Exam (MMSE) < 25

          5. HRSD ≥ 28; HRSD suicide item > 2 or the presence of significant suicide risk as judged
             by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline.

          6. Current or recent (within the past 4 weeks) treatment with antidepressants,
             antipsychotics, dopaminergic agents, or mood stabilizers.

          7. History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA

          8. Acute, severe, or unstable medical or neurological illness

          9. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar
             spine disease, mobility limiting history of joint replacement surgery, or history of
             spine surgery

             FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY:

         10. Having contraindication to MRI scanning (such as metal in body) or unable to tolerate
             the scanning procedures

         11. History of significant radioactivity exposure (nuclear medicine studies or
             occupational exposure)