The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Seventy male and female participants with depression, between 25-55 years of age, with higher levels of inflammation and anhedonia will be randomized to receive L-DOPA or matched placebo over 8 weeks. Participants will complete lab tests, medical and psychiatric assessments, motivation and motor tasks, and MRI scans as part of the study. The total length of participation is approximately 10 to 12 weeks.
Depression is a widespread disorder (lifetime prevalence \>20%). Current antidepressant medications are effective for many patients; however, more than 30% fail to respond. Of the patients that do respond to treatment, some continue to suffer with primary symptoms of depression like an inability to experience pleasure, called anhedonia. In this regard, one biological pathway that may contribute to symptoms of depression and particularly anhedonia is inflammation. The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Despite evidence of low dopamine function in patients with depression, the ability of existing dopaminergic therapies, like L-DOPA, to affect brain circuits in depression has yet to be explored. This study will help determine whether an FDA-approved medication, Sinemet (L-DOPA), might be used in the future to treat sub-groups of depressed individuals. Seventy male and female participants with depression, between 25-55 years of age, with higher levels of inflammation and anhedonia will be randomized to receive L-DOPA or matched placebo over 8 weeks. Participants will complete lab tests, medical and psychiatric assessments, motivation and motor tasks, and MRI scans as part of the study. The total length of participation is approximately 10 to 12 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
70
Patients will receive between one and three tablets per day of 150 mg L-DOPA (administered with 37.5 mg carbidopa) to achieve doses ranging from 150 to 450 mg/day.
A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive between one and three placebo tablets per day matching the Carbidopa Levodopa tablet.
Emory University Hospital
Atlanta, Georgia, United States
RECRUITINGChange in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)
The HAM-D-17 is a 17-item, clinician administered scale, that rates severity of depression. Each item is rated on a scale 0-4 with higher scores indicating greater pathology.
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in corticostriatal functional connectivity (FC) in reward circuits
Patients will undergo resting-state and task-based functional magnetic resonance imaging (fMRI) to calculate functional connectivity (FC) between the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions. Higher FC Z scores reflect stronger connectivity.
Time frame: Baseline, week 4 post-intervention, week 8 post-intervention
Change in objective motivation assessed by Effort-Expenditure for Rewards Task (EEfRT)
The EEfRT is a widely used, multi-trial task in which participants are given an opportunity on each trial to choose between two different task difficulty levels in order to obtain monetary rewards. EEfRT will be used as an objective measure of motivation, and will be administered following MRI scans during the study. The EEfRT is reported as the percent of high effort trials selected. A higher percentage reflects higher motivation for effort expenditure.
Time frame: Baseline, week 4 post-intervention, week 8 post-intervention
Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)
Anhedonia will be assessed from a subscale of the IDS-SR. Scores on this 3-question scale range from 0-9 with higher scores reflecting greater anhedonia.
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)
The SHAPS-C is a clinician administered tool to assess symptoms of anhedonia. The SHAPS-C uses14 questions each rated on a Likert scale of 1-4, with higher scores reflecting greater pathology.
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
Change in Motivation and Pleasure-Self-Report (MAP-SR)
The MAP-SR will be used to capture self-reported aspects of anhedonia and reduced motivation. The scale uses 18 questions each rated on a Likert scale of 0-4, with higher scores reflecting greater pathology.
Time frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
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