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Norepinephrine-Dopamine Reuptake Inhibitor

Antidepressants for Depression

Phase 4
Recruiting
Led By Diego A. Pizzagalli, PhD
Research Sponsored by Mclean Hospital
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Diagnosis of Major Depressive Disorder (MDD) via the Structured Clinical Interview for DSM-5 (SCID-5)
Normal or corrected-to-normal vision and hearing
Must not have
Serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems (contraindication to bupropion)- confirmed with ECG at physicians' discretion
Serious or unstable medical illness
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 8-10 weeks
Awards & highlights
Drug Has Already Been Approved
No Placebo-Only Group
Pivotal Trial

Summary

This trial will help researchers understand how different types of antidepressants affect people with depression before treatment begins.

Who is the study for?
Adults aged 18-64 with Major Depressive Disorder and high anhedonia symptoms, fluent in English, with good vision/hearing. Must be right-handed and able to consent to the study. Excludes pregnant women, those with metal implants or severe medical conditions, substance abuse issues, certain mental health disorders, history of adverse reactions to trial drugs (Sertraline/Bupropion), treatment-resistant depression or specific medication use.
What is being tested?
The SMART Trial is testing whether Sertraline or Bupropion is more effective for treating anhedonia in depression. It uses behavioral assessments and brain imaging to predict which antidepressant will work best before starting treatment.
What are the potential side effects?
Possible side effects include nausea, headaches, dry mouth for Sertraline; seizures risk (rare), dry mouth, insomnia for Bupropion. Both can cause changes in weight/appetite and mood swings.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I have been diagnosed with Major Depressive Disorder.
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My vision and hearing are normal, or corrected to be normal.
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I am between 18 and 64 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have serious heart problems as confirmed by an ECG.
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I do not have any serious or unstable illnesses.
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I have tried sertraline and bupropion without improvement.
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I am receiving or have received electroconvulsive therapy for my current health condition.
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I used marijuana regularly before I turned 15.
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I have had bad reactions or am considered unsafe to take bupropion or sertraline.
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I have tried at least two antidepressants without improvement.
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I am pregnant or might be pregnant.
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I have hemophilia, poorly controlled diabetes, chronic migraines, or a history of dementia.
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I have had a severe head injury or concussion with significant aftereffects.
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I haven't taken any blood flow or pressure medication in the last 3 weeks.
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I have a history of seizures.
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I have taken Metformin in the last 6 months.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~8-10 weeks
This trial's timeline: 3 weeks for screening, Varies for treatment, and 8-10 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Mental Depression
Secondary study objectives
Cortico-insular activation during an effort-based task
Effort-based decision making during an effort-based task
Resting state functional connectivity between the NAc and mPFC during an fMRI scan
+2 more

Side effects data

From 2002 Phase 4 trial • 110 Patients • NCT00000378
3%
orthostatic hypotension
100%
80%
60%
40%
20%
0%
Study treatment Arm
Sertaline
Nortriptyline

Awards & Highlights

Drug Has Already Been Approved
The FDA has already approved this drug, and is just seeking more data.
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Pivotal Trial
The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups
Experimental Treatment
Group I: MDD with SERT+ Response MarkerExperimental Treatment2 Interventions
Participants with MDD who have been classified as high sertraline responders based on behavioral and brain data.
Group II: MDD with BUP+ Response MarkerExperimental Treatment2 Interventions
Participants with MDD who have been classified as high bupropion responders based on behavioral and brain data.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Bupropion
2011
Completed Phase 4
~3310
Sertraline
2002
Completed Phase 4
~5470

Find a Location

Who is running the clinical trial?

Mclean HospitalLead Sponsor
216 Previous Clinical Trials
21,690 Total Patients Enrolled
47 Trials studying Depression
3,679 Patients Enrolled for Depression
Diego A. Pizzagalli, PhDPrincipal InvestigatorMclean Hospital
2 Previous Clinical Trials
187 Total Patients Enrolled
2 Trials studying Depression
187 Patients Enrolled for Depression

Media Library

Bupropion (Norepinephrine-Dopamine Reuptake Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05537584 — Phase 4
Depression Research Study Groups: MDD with BUP+ Response Marker, MDD with SERT+ Response Marker
Depression Clinical Trial 2023: Bupropion Highlights & Side Effects. Trial Name: NCT05537584 — Phase 4
Bupropion (Norepinephrine-Dopamine Reuptake Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05537584 — Phase 4
Depression Patient Testimony for trial: Trial Name: NCT05537584 — Phase 4
~58 spots leftby Dec 2025