L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
| Status: | Recruiting |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 59 - Any |
| Updated: | 2/8/2019 |
| Start Date: | January 9, 2019 |
| End Date: | November 30, 2021 |
| Contact: | Emily Valente, MS |
| Email: | emily.valente@nyspi.columbia.edu |
| Phone: | 646-774-6704 |
Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression
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.
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.
90 adults aged > 60 years with (1) a DSM 5 depressive disorder, (2) significant depressive
symptoms, and (3) decreased thinking or walking speed will receive 8 weeks of treatment with
L-DOPA up to 450mg. We will test whether L-DOPA increases brain dopamine release using
neuroimaging and whether it speeds up thinking and walking speed. Data collected in the
proposed studies may help identify a new treatment for LLD, which could have large public
health ramifications given the prevalence, frequent treatment resistance, and chronicity
characteristic of LLD. This project also will elucidate the neurobiology of slowing at
molecular, structural, and functional levels of analysis, increasing our understanding of the
interplay between these aging-associated processes and the pathophysiologic changes
underlying late life neuropsychiatric disorders. Exploring patient characteristics that
predict response to L-DOPA may provide useful information to guide differential therapeutics
and develop personalized medicine for LLD
symptoms, and (3) decreased thinking or walking speed will receive 8 weeks of treatment with
L-DOPA up to 450mg. We will test whether L-DOPA increases brain dopamine release using
neuroimaging and whether it speeds up thinking and walking speed. Data collected in the
proposed studies may help identify a new treatment for LLD, which could have large public
health ramifications given the prevalence, frequent treatment resistance, and chronicity
characteristic of LLD. This project also will elucidate the neurobiology of slowing at
molecular, structural, and functional levels of analysis, increasing our understanding of the
interplay between these aging-associated processes and the pathophysiologic changes
underlying late life neuropsychiatric disorders. Exploring patient characteristics that
predict response to L-DOPA may provide useful information to guide differential therapeutics
and develop personalized medicine for LLD
Inclusion Criteria:
- Age >59 years
- DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise
Specified
- Center for Epidemiological Studies Depression (CES-D) Rating Scale >9
- 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)
- willing to and capable of providing informed consent and complying with study
procedures
- prefer not to be treated with a standard treatment for MDD, Dysthymia, or Depression
NOS (e.g., antidepressant medication or psychotherapy).
Exclusion Criteria:
- diagnosis of substance abuse
- history of or current psychosis, psychotic disorder, mania, or bipolar disorder
- diagnosis of probable Alzheimer's Disease, Vascular Dementia, or PD
- Mini Mental Status Exam (MMSE) < 25
- HRSD ≥ 25 or the presence of significant suicide risk
- current or recent (within the past 4 weeks) treatment with antidepressants,
antipsychotics, dopaminergic agents, or mood stabilizers
- history of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA
- acute, severe, or unstable medical or neurological illness
- 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:
- having contraindication to MRI scanning (such as metal in body) or unable to tolerate
the scanning procedures
- history of significant radioactivity exposure (nuclear medicine studies or
occupational exposure)
We found this trial at
1
site
1051 Riverside Dr
New York, New York 10032
New York, New York 10032
646-774-5000
Principal Investigator: Bret R Rutherford, MD
Phone: 646-772-6704
New York State Psychiatric Institute The New York State Psychiatric Institute (NYSPI), established in 1895,...
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