Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
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|ClinicalTrials.gov Identifier: NCT04352101|
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : January 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Major Depression||Drug: Bupropion XL Drug: Escitalopram||Phase 4|
The goal of the proposed research is to determine the mechanism of action of an antidepressant of known efficacy (bupropion) and to tie this mechanism of action to a biomarker of inflammation in support of precision medicine for the treatment of major depression (MD). MD is a devastating disease affecting approximately 10% of US adults and being the leading cause of disability worldwide. Despite availability of several classes of antidepressant medications, initial treatment response is low (around 30%), and approximately 1/3 of depressed patients are non-responsive to conventional antidepressant therapies. Although extensive reviews of the literature suggest that available antidepressant medications are equally effective, recent studies suggest that there may be differential responsiveness to conventional antidepressants among subgroups of depressed patients. One subgroup of depressed patients who may exhibit differential antidepressant responsiveness are those with increased markers of inflammation. Data from previous studies support the notion that differential responsiveness to conventional antidepressants exists and may be revealed by pretreatment levels of inflammation as indexed by the inflammatory biomarker C-reactive protein (CRP).
This study proposes to use a mechanistic clinical trial design with drugs of known efficacy to take the first step toward establishing whether antidepressants that target dopamine (e.g. bupropion) might be a better choice for depressed patients with increased inflammation and anhedonia than an selective serotonin reuptake inhibitor (SSRI). Accordingly, 50 depressed patients with a CRP>2mg/L and increased anhedonia will be randomized to 8 weeks of bupropion or escitalopram in order to analyze data from 40 patients (accounting for drop outs). All depressed patients will undergo functional magnetic resonance imaging (fMRI) to examine functional connectivity in reward-related circuits at baseline and 4 and 8 weeks along with objective and clinical assessments of Research Domain Criteria (RDoC) positive (motivational) valence constructs at baseline and 2, 4, 6 and 8 weeks.
The researchers hypothesize that patients who receive bupropion versus escitalopram will exhibit increased functional connectivity between ventral striatum and ventromedial prefrontal cortex in association with decreased motivational deficits and anhedonia.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Effects of Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits in Patients With Major Depression and Increased Inflammation and Anhedonia|
|Actual Study Start Date :||September 23, 2020|
|Estimated Primary Completion Date :||May 2022|
|Estimated Study Completion Date :||May 2022|
Participants randomized to take bupropion for 8 weeks.
Drug: Bupropion XL
Participants will take 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose will be increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.
Other Name: Wellbutrin
Active Comparator: Escitalopram
Participants randomized to take escitalopram for 8 weeks.
Participants will take 10mg/d of escitalopram for two weeks, then the dose will be increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Other Name: Lexapro
- Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC) [ Time Frame: Baseline, Week 4, Week 8 ]Targeted FC will be calculated as the degree of correlation in activity between a 3mm3 radius sphere in VS and the vmPFC cluster identified as being reward-sensitive in neuroimaging meta-analyses and as used to define vmPFC in previous work. Z-scores will be extracted and the change in mean FC values compared to baseline will be calculated.
- Change in Effort-Expenditure for Rewards Task (EEfRT) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]The EEfRT task is a multi-trial game in which participants are given an opportunity to choose different task difficulty levels to obtain monetary rewards (easy tasks have low rewards while hard tasks have higher rewards). The task is 20 min, and first 50 trials are analyzed. Each trial has a high, medium, or low probability of success, and this information is given to the participant when they are deciding between easy and hard tasks. The proportion of hard-task choices across each level of probability is calculated. Lower proportions of hard task choices indicate decreased motivation.
- Change in Snaith-Hamilton Pleasure Scale (SHAPS-C) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]The SHAPS-C is a 14-item clinician-administered scale assessing the amount of pleasure during common daily activities that the participant has experienced in the past week. Responses are given on a scale of 1 to 4 where 1 = lots of pleasure and 4 = no pleasure. Total scores range from 14 to 56 with lower scores indicating greater enjoyment of activities.
- Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]The MAP-SR is an 18-item self-report inventory that has been validated in psychiatric populations and is designed to disentangle motivational and consummatory components of everyday activities over a 24-hr period. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 72 and higher scores indicate greater motivation and pleasure during everyday activities.
- Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]The 16 item QIDS-SR is a self-reported measurement of depression severity. Responses are given on a 4-point scale where 0 = no problems and 3 = severe problems. Respondents provide answers for 14 of the 16 items (depending on their symptoms). Total scores range from 0 to 42 with higher scores indicating more severe symptoms of depression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04352101
|Contact: Bobbi Woolwine, LCSWfirstname.lastname@example.org|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Andrew Miller, MD||Emory University|