DepressionPhase 4ADEPTNCT05487885
Anhedonia, Development, and Emotions: Phenotyping and Therapeutics
A Phase 4 study testing Continuous theta burst stimulation (cTBS), Positive Affect Training and Ketamine Injectable Solution in people with Depression and Anhedonia, run by Erika Forbes at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 15 to 25 years
- Conditions the study is for
- Depression, Anhedonia
- What is being tested?
- Continuous theta burst stimulation (cTBS), Positive Affect Training and Ketamine Injectable Solution
- Type of treatment
- Injection or infusion, Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2022to 1 Jun 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Depression, Anhedonia
- Being tested
- Continuous theta burst stimulation (cTBS), Positive Affect Training, Ketamine Injectable Solution
- Keywords
- depression, anhedonia
- Medical subject headings
- Depression, Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous theta burst stimulation (cTBS)Device
a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC)
Positive Affect TrainingBehavioural
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.
Ketamine Injectable SolutionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| TMS and PAT | Experimental | All open label with no randomization to placebo Receives: Device: Continuous theta burst stimulation (cTBS); Behavioral: Positive Affect Training |
| TMS and PAT, then Ketamine | Experimental | All open label with no randomization to placebo Receives: Device: Continuous theta burst stimulation (cTBS); Behavioral: Positive Affect Training; Drug: Ketamine Injectable Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS) Score
This clinician-rated scale captures depression severity on a scale of 0-60, with higher scores reflecting greater severity
Measured: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)
Secondary outcomes (1)
Snaith Hamilton Pleasure Scale (SHAPS) Score
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.
Measured: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2022
- Study start22 Jul 2022
- Primary completion19 Dec 2024
- Study completion1 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (63)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study has a longitudinal design in which participants complete 2 sets of activities: Phase 1: Phenotyping. This includes assessment with diagnostic interview, questionnaires, behavioral tasks, MRI, app-based digital assessment, and blood draw for inflammatory markers. This set of activities will occur at 4 time points over the course of 1 year/participant (study entry, approximately 4 months, approximately 5 months, and approximately 1 year), and all participants will complete them. Phase 2: Therapeutic activities: (1) 10 theta burst stimulation (TBS) sessions (TBS 2 times/session) plus positive affect (PA) training for all participants; and (2) IV ketamine infusion for those who do not respond to TBS/PA activities.
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erika Forbes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Erika Forbes, University of Pittsburgh
- Investigators
- Erika E Forbes, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05487885
- Sponsor's protocol ID
- STUDY21120080
- Acronym
- ADEPT
- Status last verified
- Feb 2026
- First submitted
- 27 Jul 2022
- Last updated
- 17 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Aquino D, Bizzi A, Grisoli M, Garavaglia B, Bruzzone MG, Nardocci N, Savoiardo M, Chiapparini L. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology. 2009 Jul;252(1):165-72. doi: 10.1148/radiol.2522081399.
PubMed 19561255Belujon P, Grace AA. Dopamine System Dysregulation in Major Depressive Disorders. Int J Neuropsychopharmacol. 2017 Dec 1;20(12):1036-1046. doi: 10.1093/ijnp/pyx056.
PubMed 29106542Berridge KC. Evolving Concepts of Emotion and Motivation. Front Psychol. 2018 Sep 7;9:1647. doi: 10.3389/fpsyg.2018.01647. eCollection 2018.
PubMed 30245654Boyle CC, Kuhlman KR, Dooley LN, Haydon MD, Robles TF, Ang YS, Pizzagalli DA, Bower JE. Inflammation and dimensions of reward processing following exposure to the influenza vaccine. Psychoneuroendocrinology. 2019 Apr;102:16-23. doi: 10.1016/j.psyneuen.2018.11.024. Epub 2018 Nov 20.
PubMed 30496908Brenhouse HC, Schwarz JM. Immunoadolescence: Neuroimmune development and adolescent behavior. Neurosci Biobehav Rev. 2016 Nov;70:288-299. doi: 10.1016/j.neubiorev.2016.05.035. Epub 2016 May 31.
PubMed 27260127Brundin L, Bryleva EY, Thirtamara Rajamani K. Role of Inflammation in Suicide: From Mechanisms to Treatment. Neuropsychopharmacology. 2017 Jan;42(1):271-283. doi: 10.1038/npp.2016.116. Epub 2016 Jul 5.
PubMed 27377015Cassidy CM, Zucca FA, Girgis RR, Baker SC, Weinstein JJ, Sharp ME, Bellei C, Valmadre A, Vanegas N, Kegeles LS, Brucato G, Kang UJ, Sulzer D, Zecca L, Abi-Dargham A, Horga G. Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5108-5117. doi: 10.1073/pnas.1807983116. Epub 2019 Feb 22.
PubMed 30796187Chase HW, Fournier JC, Bertocci MA, Greenberg T, Aslam H, Stiffler R, Lockovich J, Graur S, Bebko G, Forbes EE, Phillips ML. A pathway linking reward circuitry, impulsive sensation-seeking and risky decision-making in young adults: identifying neural markers for new interventions. Transl Psychiatry. 2017 Apr 18;7(4):e1096. doi: 10.1038/tp.2017.60.
PubMed 28418404Chen X, Huddleston DE, Langley J, Ahn S, Barnum CJ, Factor SA, Levey AI, Hu X. Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach. Magn Reson Imaging. 2014 Dec;32(10):1301-6. doi: 10.1016/j.mri.2014.07.003. Epub 2014 Jul 31.
PubMed 25086330Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia. 1996 Jun;17(2):83-93. doi: 10.1002/(SICI)1098-1136(199606)17:23.0.CO;2-7.
PubMed 8776576Cosgrove KT, Burrows K, Avery JA, Kerr KL, DeVille DC, Aupperle RL, Teague TK, Drevets WC, Simmons WK. Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry. Brain Behav Immun. 2020 Jan;83:163-171. doi: 10.1016/j.bbi.2019.10.006. Epub 2019 Oct 8.
PubMed 31604141Craske MG, Meuret AE, Ritz T, Treanor M, Dour HJ. Treatment for Anhedonia: A Neuroscience Driven Approach. Depress Anxiety. 2016 Oct;33(10):927-938. doi: 10.1002/da.22490.
PubMed 27699943Craske MG, Meuret AE, Ritz T, Treanor M, Dour H, Rosenfield D. Positive affect treatment for depression and anxiety: A randomized clinical trial for a core feature of anhedonia. J Consult Clin Psychol. 2019 May;87(5):457-471. doi: 10.1037/ccp0000396.
PubMed 30998048Der-Avakian A, Barnes SA, Markou A, Pizzagalli DA. Translational Assessment of Reward and Motivational Deficits in Psychiatric Disorders. Curr Top Behav Neurosci. 2016;28:231-62. doi: 10.1007/7854_2015_5004.
PubMed 26873017Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci. 2012 Jan;35(1):68-77. doi: 10.1016/j.tins.2011.11.005. Epub 2011 Dec 15.
PubMed 22177980
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anhedonia, Development, and Emotions: Phenotyping and Therapeutics (ADEPT) Study
- ClinicalTrials.gov ID
- NCT05487885
- Acronym / sponsor ID
- ADEPT / STUDY21120080
- Conditions
- Depression, Anhedonia
- Keywords
- depression, anhedonia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Erika ForbesUniversity, hospital or other
- Study start
- 22 Jul 2022 (actual)
- Primary completion
- 19 Dec 2024 (actual)
- Study completion
- 1 Jun 2025 (actual)
- First posted
- 4 Aug 2022 (actual)
- Results
- Posted 17 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study has a longitudinal design in which participants complete 2 sets of activities: Phase 1: Phenotyping. This includes assessment with diagnostic interview, questionnaires, behavioral tasks, MRI, app-based digital assessment, and blood draw for inflammatory markers. This set of activities will occur at 4 time points over the course of 1 year/participant (study entry, approximately 4 months, approximately 5 months, and approximately 1 year), and all participants will complete them. Phase 2: Therapeutic activities: (1) 10 theta burst stimulation (TBS) sessions (TBS 2 times/session) plus positive affect (PA) training for all participants; and (2) IV ketamine infusion for those who do not respond to TBS/PA activities.
| Arm | Type | Receives |
|---|---|---|
| TMS and PAT | Experimental | Device: Continuous theta burst stimulation (cTBS), Behavioral: Positive Affect TrainingAll open label with no randomization to placebo |
| TMS and PAT, then Ketamine | Experimental | Device: Continuous theta burst stimulation (cTBS), Behavioral: Positive Affect Training, Drug: Ketamine Injectable SolutionAll open label with no randomization to placebo |
Who may qualify
- Ages
- 15 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous theta burst stimulation (cTBS)a form of transcranial magnetic stimulation, to dorsomedial prefrontal cortex (dmPFC) | Device | TMS and PAT, TMS and PAT, then Ketamine |
| Positive Affect TrainingPsychosocial 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. | Behavioural | TMS and PAT, TMS and PAT, then Ketamine |
| Ketamine Injectable SolutionKetamine 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. | Drug | TMS and PAT, then Ketamine |
Primary outcome
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
1 secondary outcome
Snaith Hamilton Pleasure Scale (SHAPS) Score
Time frame: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19561255Aquino D, Bizzi A, Grisoli M, Garavaglia B, Bruzzone MG, Nardocci N, Savoiardo M, Chiapparini L. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology. 2009 Jul;252(1):165-72. doi: 10.1148/radiol.2522081399.
- Background: PubMed 29106542Belujon P, Grace AA. Dopamine System Dysregulation in Major Depressive Disorders. Int J Neuropsychopharmacol. 2017 Dec 1;20(12):1036-1046. doi: 10.1093/ijnp/pyx056.
- Background: PubMed 30245654Berridge KC. Evolving Concepts of Emotion and Motivation. Front Psychol. 2018 Sep 7;9:1647. doi: 10.3389/fpsyg.2018.01647. eCollection 2018.
- Background: PubMed 30496908Boyle CC, Kuhlman KR, Dooley LN, Haydon MD, Robles TF, Ang YS, Pizzagalli DA, Bower JE. Inflammation and dimensions of reward processing following exposure to the influenza vaccine. Psychoneuroendocrinology. 2019 Apr;102:16-23. doi: 10.1016/j.psyneuen.2018.11.024. Epub 2018 Nov 20.
- Background: PubMed 27260127Brenhouse HC, Schwarz JM. Immunoadolescence: Neuroimmune development and adolescent behavior. Neurosci Biobehav Rev. 2016 Nov;70:288-299. doi: 10.1016/j.neubiorev.2016.05.035. Epub 2016 May 31.
- Background: PubMed 27377015Brundin L, Bryleva EY, Thirtamara Rajamani K. Role of Inflammation in Suicide: From Mechanisms to Treatment. Neuropsychopharmacology. 2017 Jan;42(1):271-283. doi: 10.1038/npp.2016.116. Epub 2016 Jul 5.
- Background: PubMed 30796187Cassidy CM, Zucca FA, Girgis RR, Baker SC, Weinstein JJ, Sharp ME, Bellei C, Valmadre A, Vanegas N, Kegeles LS, Brucato G, Kang UJ, Sulzer D, Zecca L, Abi-Dargham A, Horga G. Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. Proc Natl Acad Sci U S A. 2019 Mar 12;116(11):5108-5117. doi: 10.1073/pnas.1807983116. Epub 2019 Feb 22.
- Background: PubMed 28418404Chase HW, Fournier JC, Bertocci MA, Greenberg T, Aslam H, Stiffler R, Lockovich J, Graur S, Bebko G, Forbes EE, Phillips ML. A pathway linking reward circuitry, impulsive sensation-seeking and risky decision-making in young adults: identifying neural markers for new interventions. Transl Psychiatry. 2017 Apr 18;7(4):e1096. doi: 10.1038/tp.2017.60.
- Background: PubMed 25086330Chen X, Huddleston DE, Langley J, Ahn S, Barnum CJ, Factor SA, Levey AI, Hu X. Simultaneous imaging of locus coeruleus and substantia nigra with a quantitative neuromelanin MRI approach. Magn Reson Imaging. 2014 Dec;32(10):1301-6. doi: 10.1016/j.mri.2014.07.003. Epub 2014 Jul 31.
- Background: PubMed 8776576Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia. 1996 Jun;17(2):83-93. doi: 10.1002/(SICI)1098-1136(199606)17:23.0.CO;2-7.
- Background: PubMed 31604141Cosgrove KT, Burrows K, Avery JA, Kerr KL, DeVille DC, Aupperle RL, Teague TK, Drevets WC, Simmons WK. Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry. Brain Behav Immun. 2020 Jan;83:163-171. doi: 10.1016/j.bbi.2019.10.006. Epub 2019 Oct 8.
- Background: PubMed 27699943Craske MG, Meuret AE, Ritz T, Treanor M, Dour HJ. Treatment for Anhedonia: A Neuroscience Driven Approach. Depress Anxiety. 2016 Oct;33(10):927-938. doi: 10.1002/da.22490.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erika E Forbes, PhD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuous theta burst stimulation (cTBS), Positive Affect Training and Ketamine Injectable Solution in people with Depression and Anhedonia, run by Erika Forbes at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) Score (time frame: pre- to post-TMS (over 2 weeks) and pre- to post-ketamine (24 hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05487885, which also lists 63 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.