Dopaminergic Dysfunction in Late-Life Depression

Completed · Phase 2 · Has a placebo group

Conditions studied: Late Life Depression, Cognitive Decline, Depressive Disorder, Treatment-Resistant, Levodopa, Gait Impairment

In brief

Late-Life Depression (LLD), or depression in older adults, often presents with motivational deficits, deficits in performance in cognitive domains including processing speed and executive dysfunction, and mobility impairments. This triad of findings implicate dopaminergic dysfunction as a core pathophysiologic feature in depression, and may contribute to cognitive decline and motor disability. Normal aging results in brain-wide dopamine declines, decreased D1/D2 receptor density, and loss of dopamine transporters. Although brain changes associated with depression and aging converge on dopamine circuits, the specific disturbances in LLD and how responsive the system is to modulation remain unclear. In this study, investigators are testing integrative model that aging, in concert with pro-inflammatory shifts, decreases dopamine signaling. These signally changes affects behaviors supported by these circuits, in the context of age-associated cortical atrophy and ischemic microvascular changes, resulting in variable LLD phenotypes. Investigators propose a primary pathway where dopaminergic dysfunction in depressed elders contributes to slowed processing speed and mobility impairments that increase the effort cost associated with voluntary behavior. The central hypothesis of this study is that late-life depression is characterized by dysfunction in the dopamine system and, by enhancing dopamine functioning in the brain. By improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms.

Key facts

Study ID: NCT04469959
Run by: Vanderbilt University Medical Center
People needed: 79
Starts: 2021-02-15
Expected to finish: 2026-04-29
Last updated by the study team: 2026-08-06

Who can join

Age: 60 and older. Sex: any. Healthy volunteers: accepted.

You may qualify if…

Age ≥ 60 years
Diagnostic and Statistical Manual-5 (DSM5) diagnosis of Major Depressive Disorder, Persistent Depressive Disorder, or Depression Not Otherwise Specified (NOS)
MADRS score ≥ 15
Decreased processing speed (0.5 SD below age-adjusted norms on the WAIS-IV Coding task or Trail Making Test, Part A) or decreased motor speed (gait speed/average walking speed on 15' course ≤ 1m/s, or 0.5 SD below age-, gender- and education-adjusted norms on the grooved pegboard test)
Capable of providing informed consent and adhering to study procedures

You may not qualify if…

Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) in the past 12 months
Other psychiatric disorders including a history of psychosis, psychotic disorder, mania, or bipolar disorder. Other comorbid psychiatric disorders are allowable if the depressive disorder diagnosis is considered to be the primary problem
Primary neurological disorder, including dementia, stroke, Parkinson's disease, epilepsy, etc
SBT > 10
MADRS suicide item > 4 or other indication of acute suicidality
History of inpatient psychiatric hospitalization in the last year;
History of suicidal ideation in the last 6 months, operationalized as a 'yes' response to item 4 or 5 in the "Suicidal Ideation" section of the Columbia-Suicide Severity Rating Scale (CSSRS)
Any suicidal behavior in the last year (operationalized as a 'yes' response to any item in the "Suicidal Behavior" section of the CSSRS, including actual interrupted, aborted, or preparatory acts)
Current or recent (within the past 2 weeks) treatment with antipsychotics or mood stabilizers, or use of antidepressants where washout is not advisable
History of hypersensitivity, allergy, or intolerance to Carbidopa/levodopa
Any physical or intellectual disability adversely affecting ability to complete assessments
Unstable medical illness
Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, or history of joint replacement / spine surgery that limits mobility
Diagnosis of HIV
History of significant radioactivity exposure (nuclear medicine studies or occupational exposure).

Where it is running

University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States
Vanderbilt Psychiatric Hospital — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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