Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression - 2
Overview
- Phase
- Phase 4
- Intervention
- Carbidopa Levodopa
- Conditions
- Anhedonia
- Sponsor
- Emory University
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Jennifer Felger
Associate Professor
Emory University
Eligibility Criteria
Inclusion Criteria
- •a. willing and able to give written informed consent
- •b. men or women, 25-55 years of age
- •c. a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), current, as diagnosed by the Structured Clinical Interview for DSM-5
- •d. score of \>10 on the Patient Health Questionnaire-9 (PHQ-9) or HAM-D score ≥18
- •e. off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine)
- •f. c-reactive protein (CRP) ≥2 mg/L
- •g. PHQ-9 anhedonia score ≥2
Exclusion Criteria
- •a. history or evidence (clinical or laboratory) of an autoimmune disorder
- •b. history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection
- •c. history of any type of cancer requiring treatment with more than minor surgery
- •d. unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing)
- •e. history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; history or current bipolar disorder; history or current gambling disorder; substance abuse/dependence within 6 months of study entry (as determined by standardized clinician interview)
- •f. active suicidal plan as determined by a score \>3 on item #3 on the HAM-D
- •g. an active eating disorder (except for patients with binge eating disorder in whom binging is clearly associated with worsening of mood symptoms)
- •h. a history of a cognitive disorder or traumatic head injury involving loss of consciousness
- •i. pregnancy or lactation
- •j. use of gender affirming hormone therapy
Arms & Interventions
Carbidopa Levodopa Group
Patients randomized to the Carbidopa Levodopa Group will receive one tablet per day of L-DOPA (150 mg levodopa administered with 37.5 mg carbidopa) for 4 weeks. Patients that respond after the initial 4 weeks will continue on the same dose for an additional 4 weeks to determine whether clinical response at the 150 mg dose is sustained over time compared to placebo. Patients that do not exhibit a clinical response (50% reduction in HAM-D scores from baseline) after 4-weeks on the 150 mg dose will escalate to 450 mg L-DOPA (three tablets per day of 150 mg levodopa administered with 37.5 mg carbidopa) and studied over an additional 4 weeks (8 weeks total in the study).
Intervention: Carbidopa Levodopa
Placebo Group
Participants will receive placebo tablet. Placebo-treated non-responders at 4 weeks will remain on placebo but with the same instructions to increase daily pill intake.
Intervention: Placebo
Outcomes
Primary Outcomes
Change in depressive symptom severity measured by Hamilton Depression Rating Scale (HAM-D)
Time Frame: Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention
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.
Secondary Outcomes
- Change in objective motivation assessed by Effort-Expenditure for Rewards Task (EEfRT)(Baseline, week 4 post-intervention, week 8 post-intervention)
- Change in Inventory of Depressive Symptomatology- Self-Report (IDS-SR)(Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention)
- Change in corticostriatal functional connectivity (FC) in reward circuits(Baseline, week 4 post-intervention, week 8 post-intervention)
- Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)(Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention)
- Change in Motivation and Pleasure-Self-Report (MAP-SR)(Baseline, weeks 1-4 post-intervention, weeks 5-8 post-intervention)