Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

NCT ID: NCT04352101

Last Updated: 2023-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-23
• Study Completion Date: 2022-07-25

Brief Summary

This study is designed to determine whether bupropion (vs escitalopram) increases functional connectivity (FC) within reward-related neurocircuits and decreases motivational deficits in depressed patients with increased inflammation and anhedonia. Participants will be randomized to take bupropion extended release (XL) or escitalopram for 8 weeks.

Detailed Description

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.

Conditions

Major Depression

Keywords

Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Bupropion

Participants randomized to take bupropion for 8 weeks.

Group Type: EXPERIMENTAL

Bupropion XL

Intervention Type: DRUG

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.

Escitalopram

Participants randomized to take escitalopram for 8 weeks.

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Escitalopram

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.

Intervention Type: DRUG

Other Intervention Names

Wellbutrin; Lexapro

Eligibility Criteria

Inclusion Criteria

• willing and able to give written informed consent
• a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) MD, current as diagnosed by the Structured Clinical Interview for DSM-V Axis I Disorders (SCID-V)
• score of ≥16 on the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)
• off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine); concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments
• CRP>2mg/L
• Inventory of Depressive Symptomatology (IDS-SR) anhedonia subscale score ≥5

Exclusion Criteria

• history of any autoimmune disorder
• history of hepatitis B or C infection or human immunodeficiency virus infection
• history of any type of cancer requiring treatment with more than minor surgery
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing)
• history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by SCID)
• an active eating disorder or antisocial personality disorder
• a history of a cognitive disorder or ≤28 on the Mini-Mental State Exam unless otherwise approved by the PI
• pregnancy or lactation
• chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications
• use of NSAIDS or oral glucocorticoids at any time during the study
• any contraindication for MRI scanning
• failure of more than 2 antidepressant trials in the current episode
• Intolerance of bupropion or escitalopram
• BMI >40 (to exclude severe obesity)
• due to the high co-morbidity between anxiety disorders and depression, the study team plans to include patients with anxiety-related disorders excluding obsessive-compulsive disorder (OCD) if depression is the primary diagnosis. Patients with stable medical conditions and on medications for those conditions will not be excluded. Concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments.
• sexually active participants are required to use medically approved birth control methods as defined in the Birth Control Method Form for the duration of the study

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Andrew H Miller

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory Clinic

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21MH121891

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00117673

Identifier Type: -

Identifier Source: org_study_id