SMART Trial to Predict Anhedonia Response to Antidepressant Treatment

NCT05537584 | Completed Phase 4 FDA Drug

• 1 other identifier: 2022P000896
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this research is to use behavioral, brain, and clinical data to determine which type of antidepressant might be optimal before people with depression start treatment.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Score on Montgomery-Asberg Depression Rating Scale (MADRS)

  Symptoms of depression

  8-10 weeks

Secondary Outcomes (5)

• Ventral-striatal activation during reward related tasks in an fMRI scan

  8-10 weeks

• Effort-based decision making during an effort-based task

  8-10 weeks

• Reward positivity during a guessing monetary reward task

  8-10 weeks

• Cortico-insular activation during an effort-based task

  8-10 weeks

• Resting state functional connectivity between the NAc and mPFC during an fMRI scan

  8-10 weeks

Study Arms (2)

MDD with SERT+ Response Marker

EXPERIMENTAL

Participants with MDD who have been classified as high sertraline responders based on behavioral and brain data.

Drug: Sertraline; Drug: Bupropion

MDD with BUP+ Response Marker

EXPERIMENTAL

Participants with MDD who have been classified as high bupropion responders based on behavioral and brain data.

Drug: Sertraline; Drug: Bupropion

Interventions

Sertraline DRUG

Subjects will receive 8 weeks of sertraline while monitored by the study physician

Also known as: Zoloft

MDD with BUP+ Response Marker; MDD with SERT+ Response Marker

Bupropion DRUG

Subjects will receive 8 weeks of bupropion while monitored by the study physician

Also known as: Wellbutrin

MDD with BUP+ Response Marker; MDD with SERT+ Response Marker

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ages 18 to 64
• Any gender and all ethnic/racial origins
• Diagnosis of Major Depressive Disorder. MDD diagnosis will be decided by clinicians via the Structured Clinical Interview for DSM-5 (SCID-5).
• Elevated depression severity
• Elevated anhedonia symptoms
• Fluency in written and spoken English
• Ability to give signed, informed consent either written or electronic
• Normal or corrected-to-normal vision and hearing
• Ability to adhere to the study schedule

You may not qualify if:

• Patient is currently enrolled in any treatment program except psychotherapy (transcranial magnetic stimulation, other antidepressants etc.).
• Any contraindication to bupropion or sertraline considered unsafe by the study physician, or any history of adverse reaction to either drug.
• Failure to respond to an adequate course of treatment with both of the study medications (sertraline or bupropion) during the current episode.
• Participants who are determined to be treatment resistant, (i.e., having failed to respond to at least two adequate antidepressant trials in the current episode)
• Pregnant women, or women of childbearing potential who have a positive result on a urine pregnancy test
• Failure to meet MRI safety requirements, including any metal implants or prostheses that cannot be removed, or exposure to shrapnel
• Claustrophobia or severe anxiety that might affect participation in neuroimaging
• Injury or movement disorder that may make it difficult to lie still in the scanner
• Any current recreational/illicit drug use, with the exception of THC, as assessed by a urine drug test (covering cocaine, cannabinoids, opiates, amphetamines, methamphetamines, phencyclidine, MDMA, benzodiazepines, methadone, oxycodone, tricyclic antidepressants, and barbiturates). Participants who use THC regularly will be allowed to continue in the study provided they have abstained for the three days prior to visits involving the MRI scan.
• Use of Monoamine Oxidase Inhibitors (MAOIs) either currently or within the past two weeks
• Participants who are currently stopping the use of tobacco products. Participants who cannot abstain from tobacco products for eight hours without cravings.
• More than 15 alcohol-induced lifetime blackouts.
• History of regular use (5-7xs per week) of marijuana before the age of 15
• Lifetime history of other recreational drug use beyond the following limits (for each drug individually) and/or last use within the past 3 months:
• Hallucinogens (mushrooms, LSD): exclude for12 uses in the past year, or 15 uses lifetime (unless last use was 5+ years ago, then allow up to 25 lifetime uses)

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Sertraline; Bupropion

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Propiophenones; Ketones

Study Officials

• Diego A. Pizzagalli, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Psychiatry, Harvard Medical School

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 13, 2022
• Study Start: September 30, 2022
• Primary Completion: August 26, 2025
• Study Completion: August 26, 2025
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 12 months after data collection is completed
• Access Criteria: Access will be governed by the Multi-Channel Psych department of the Wellcome Leap foundation.

Locations

US (1)