Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT)

February 23, 2026 updated by: Erika Forbes

Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT) Study

The goal of the ADEPT Study is to understand anhedonia in young people and how it changes based on treatments targeting the brain circuit underlying it. Anhedonia is a challenging mental health symptom that involves difficulty with motivation to experience pleasant events. This study could help develop treatments for people whose depression does not improve with traditional treatments.

The ADEPT Study includes two phases. In Phase 1, participants are asked to go through a series of activities to measure anhedonia, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and app-based assessments of experiences and behaviors. Phase 2 involves therapeutic activities, such as transcranial magnetic stimulation (TMS), positive affect training, and, for some people, ketamine administration. If the participant qualifies and is interested, they may choose to do Phase 2 activities in addition to Phase 1.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In this research study, the investigators are trying to understand and change anhedonia in young people with depression. Anhedonia is experienced by many people who have depression, and it involves difficulty with motivation, energy, and anticipation of pleasant events. People who experience anhedonia often have more severe depression, experience depression for longer periods of time, and don't easily get better with traditional treatments. The investigators want to understand anhedonia early in life in order to help young people develop along healthy pathways and avoid chronic illness. Anhedonia is related to function in the brain's reward circuit, inflammation in the body, and people's experiences and behaviors, and will measure all of these. The investigators also want to understand anhedonia by using treatments that could improve it. To do that, activities will be used that have been used to treat depression and target the brain's reward circuit, which is believed to be the source of anhedonia. Finally, anhedonia will be measured over approximately 1 year to see how it changes with time, development, or treatment-based experiences. Eventually, the findings of this study might be useful for treating depression and improving people's quality of life.

The study is looking for 300 young people (aged 15-25) who are currently experiencing depression to participate in our research study. In Phase 1 of our study, a series of activities will be conducted to understand the characteristics of anhedonia, including MRI scans, blood draws, behavioral tasks, clinical interviews, questionnaires, and measurement of real-life experiences and behavior using a phone app. This is called "phenotyping" because these characteristics are also called phenotypes.

The eligibility process for Phase 1 will include an interview with questions about the participant's mood, experiences, and behaviors. This interview will take approximately 2-3 hours. With permission, interviews will be video recorded to facilitate training and supervision of study staff. Participants will also be asked questions about health, including treatment history.

Study procedures include 4 visits over approximately 1 year. These may be broken into two sessions per visit for scheduling reasons. In addition, the study will include an ongoing smartphone app-based assessment of mood, experiences, and behavior.

Visit 1 consists of an MRI scan, questionnaires about thoughts, emotions, and experiences, tasks on a computer and a blood draw by a trained phlebotomist. Visits 2-4 consists of a second MRI scan, questionnaires, tasks on a computer, a blood draw by a trained phlebotomist, and an interview about mood, experiences, and behaviors.

Phase 2 of this study involves procedures that are therapeutic, meaning they can treat depression and anhedonia. These include transcranial magnetic stimulation (TMS), which is a noninvasive procedure to treat depression that uses magnetic fields to stimulate nerve cells in the brain. Visits with TMS will include Positive Affect Training, which involves changing behaviors and thoughts to build positive emotions. People whose depression does not improve with TMS may receive a single intravenous (IV, or into the vein) infusion of ketamine, a medicine that is used in hospitals for anesthesia and that can improve depression quickly.

Study Type

Interventional

Enrollment (Actual)

123

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Loeffler Building

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Phase 1 (all participants)

  • Current DSM-5 depressive disorder
  • Severity ≥ 12 on MADRS
  • Moderate-severe anhedonia (75% of sample) or low anhedonia (25% of sample)

Phase 2 (for participants in TBS and ketamine phase, in addition to above)

• ≥ 1 failed antidepressant trial (for qualification for Phase 2 of study and definition of non-response to TMS in order to be eligible for ketamine) = Treatment for at least 6 weeks with an antidepressant medication reaching recommended dosage for adults for at least 3 weeks of the treatment (e.g., 20 mg fluoxetine)

Exclusion Criteria:

Phase 1 (all participants)

  • Lifetime psychosis, bipolar disorder, or developmental disorder
  • Serious, unstable neurological disorder (e.g., seizure disorder)
  • Brain injury with loss of consciousness
  • Moderate-severe substance use disorder, past 6 mos.
  • MRI contraindications (e.g., metal in body)

Phase 2 (for participants in TBS and ketamine phase, in addition to above)

  • Serious, unstable respiratory or cardiovascular illness
  • Pre-TBS: Alcohol binge in past week or > 3 drinks/day in past 3 days
  • Pre-ketamine: use of MAOIs in past 2 weeks
  • Pregnancy
  • High blood pressure
  • Current illicit stimulant use
  • Lifetime recreational ketamine or PCP use

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMS and PAT
All open label with no randomization to placebo
Device: Continuous theta burst stimulation (cTBS)
a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)
Behavioral: Positive Affect Training
Psychosocial add-on intervention that could enhance the effects of TBS. PA Therapy (Craske et al., 2016) is an innovative cognitive and experiential technique developed to address anhedonia specifically and, ideally, change altered patterns of frontostriatal function. Standing in contrast to Cognitive Behavioral Therapy, PA training has efficacy for enhancing positive affect and reducing negative affect (Craske et al., 2018). This treatment can be easily applied, and we propose that it will enhance neural circuit-level changes elicited by TBS.
Experimental: TMS and PAT, then Ketamine
All open label with no randomization to placebo
Device: Continuous theta burst stimulation (cTBS)
a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)
Behavioral: Positive Affect Training
Psychosocial add-on intervention that could enhance the effects of TBS. PA Therapy (Craske et al., 2016) is an innovative cognitive and experiential technique developed to address anhedonia specifically and, ideally, change altered patterns of frontostriatal function. Standing in contrast to Cognitive Behavioral Therapy, PA training has efficacy for enhancing positive affect and reducing negative affect (Craske et al., 2018). This treatment can be easily applied, and we propose that it will enhance neural circuit-level changes elicited by TBS.
Drug: Ketamine Injectable Solution
Ketamine is FDA-approved as an anesthetic agent that will be used off-label in this study. It is used routinely in both pediatric and adult patients and is considered extremely safe in substantially higher, anesthetic doses. The dose to be administered here (0.5 mg/kg) is a much lower, subanesthetic dose, and the administration route (intravenous) is the standard when used in anesthesia. Published studies and metaanalyses of this dose of intravenous ketamine as an off label use in depression show clearly that there are no increased risks in this population, including a recent study in adolescents (Dwyer et al, 2021, American Journal of Psychiatry). A single dose of ketamine will be used to determine if it alters the functioning of the anhedonia-related reward functioning and frontostriatal biomarkers assessed in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time Frame: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)
This clinician-rated scale captures depression severity on a scale of 0-60, with higher scores reflecting greater severity
pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Snaith Hamilton Pleasure Scale (SHAPS) Score
Time Frame: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)
This 14-item self-report questionnaire measures anhedonia, or difficulty with motivation toward or enjoyment of pleasant events. Total scores range from 14-56, with higher scores reflecting greater severity.
pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erika Forbes

Investigators

  • Principal Investigator: Erika E Forbes, PhD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 22, 2022

Primary Completion (Actual)

December 19, 2024

Study Completion (Actual)

June 1, 2025

Study Registration Dates

First Submitted

July 27, 2022

First Submitted That Met QC Criteria

August 3, 2022

First Posted (Actual)

August 4, 2022

Study Record Updates

Last Update Posted (Actual)

March 17, 2026

Last Update Submitted That Met QC Criteria

February 23, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY21120080

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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