Treatment Resistant DepressionNCT03428828
Neurofeedback for Treatment Resistant Depression
A study testing Amygdala Neurofeedback and Parietal Neurofeedback in people with Treatment Resistant Depression, run by Kymberly Young at 1 site in United States.
Trial summary
The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Amygdala Neurofeedback and Parietal Neurofeedback
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2018to 1 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- right-handed adults (ages 18 - 55) with a primary diagnosis of MDD according to diagnostic criteria DSM-5 for recurrent MDD who are currently depressed will be recruited to participate
- must be able to give written informed consent prior to participation
- must have fewer than 45% memories categorized as specific on the Autobiographical Memory Test
- must have a SHAPS score > 4, indicating the presence of anhedonia
- unmedicated or stable on an SSRI antidepressant regime (at least 3 weeks to ensure symptoms are stable)
- previously failed to respond to two previous SSRI medications according to either a medical record review or clinical interview during Visit 1
Who cannot join
- have a clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
- met DSM-IV criteria for alcohol and/or substance dependence (other than nicotine) within 12 months prior to screening
- have a history of traumatic brain injury
- are unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
- are currently pregnant or breast feeding
- are unable to complete questionnaires written in English
Show all 9Show fewer
- current (within 3 weeks of testing) use of any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications (except SSRI antidepressants) likely to influence cerebral blood flow. Effective medications will not be discontinued for the purposes of the study. Inclusion of patients on stable antidepressant medications was decided in order to allow generalization towards a real world population
- have a DSM-5 diagnosis of psychotic or organic mental disorder, bipolar I or II disorder or any past or current manic or hypomanic symptoms, autism, or a primary diagnosis of an anxiety disorder (though co-morbid anxiety will not be excluded)
- have any eye problems or difficulties in corrected vision.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression
The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant
Read the detailed description
Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard pharmacological and psychological interventions and will be considered treatment resistant (TR-MDD). Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall, may be a causal mechanism interfering with recovery from TR-MDD. Previous work in our lab suggests that individuals who do respond to antidepressant medications show increased amygdala activity that is indistinguishable from controls relative to baseline, while TR-MDD individuals fail to show this increase in amygdala activity. Furthermore, the investigators have found that MDD participants (more generally, not specifically TR- MDD) are indeed able to increase their amygdala response during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that this increase is associated with large and rapid reductions in depressive symptoms. Here, the investigators propose to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as an intervention for TR-MDD. 100 TR-MDD individuals will be randomly assigned under double-blind conditions to receive 5 amygdala rtfMRI-nf or 5 control rtfMRI-nf sessions where they are trained to regulate a parietal region putatively not involved in emotional processing or MDD. The investigators will assess changes in amygdala activity, severity of clinical symptoms, and autobiographical memory deficits. Success will suggest a new non- pharmacological, non-invasive intervention for a traditionally treatment-resistant population of MDD individuals.
- Conditions
- Treatment Resistant Depression
- Being tested
- Amygdala Neurofeedback, Parietal Neurofeedback
- Keywords
- Neurofeedback, major depressive disorder, treatment resistant, amygdala
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amygdala NeurofeedbackDevice
Participants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories
Parietal NeurofeedbackDevice
Participants are shown activity from their left horizontal segment of the intraparietal sulcus in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories
| Study group | Role | What they receive |
|---|---|---|
| Amygdala Neurofeedback | Experimental | attempt to up regulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Five sessions will be performed within a 2 month period. Receives: Device: Amygdala Neurofeedback |
| Parietal Neurofeedback | Active comparator | attempt to upregulate the left horizontal segment of the intraparietal sulcus, a region not involved in emotional processing, during positive autobiographical memory recall via real time fMRI neurofeedback. Five sessions will be performed within a 2 month period. Receives: Device: Parietal Neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beck Depression Inventory (BDI-II)
Measured: 12 weeks
Secondary outcomes (1)
Amygdala Activity
% signal change from initial baseline to final transfer run in amygdala activity during ftMRI-nf sessions
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start22 Oct 2018
- Primary completion1 Mar 2026
- Study completion1 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kymberly Young
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Kymberly Young, University of Pittsburgh
- Investigators
- Kymberly Young, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03428828
- Sponsor's protocol ID
- STUDY19020313
- Other IDs
- R61MH115927
- Status last verified
- Mar 2026
- First submitted
- 1 Feb 2018
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: The final data set will include self-reported demographic and behavioral data, clinical-rated information regarding illness course, severity, and comorbidities, and brain-imaging data collected during fMRI. The dataset will be stripped of identifiers prior to release for sharing, and will be shared openly and timely in accordance with the most recent NIH guidelines. Data will be shared every six months on the NIH-supported National Database for Clinical Trials Related to Mental Illness (NDCT) data repository.
Publications
Young KD, Siegle GJ, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall. Am J Psychiatry. 2017 Aug 1;174(8):748-755. doi: 10.1176/appi.ajp.2017.16060637. Epub 2017 Apr 14.
PubMed 28407727Compere L, Siegle GJ, Lazzaro S, Riley E, Strege M, Canovali G, Barb S, Huppert T, Young K. Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination. Behav Res Ther. 2024 May;176:104523. doi: 10.1016/j.brat.2024.104523. Epub 2024 Mar 15.
PubMed 38513424
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT03428828
- Acronym / sponsor ID
- STUDY19020313
- Conditions
- Treatment Resistant Depression
- Keywords
- Neurofeedback, major depressive disorder, treatment resistant, amygdala
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Kymberly YoungUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 22 Oct 2018 (actual)
- Primary completion
- 1 Mar 2026 (actual)
- Study completion
- 1 Mar 2026 (actual)
- First posted
- 12 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant
Detailed description
Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard pharmacological and psychological interventions and will be considered treatment resistant (TR-MDD). Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall, may be a causal mechanism interfering with recovery from TR-MDD. Previous work in our lab suggests that individuals who do respond to antidepressant medications show increased amygdala activity that is indistinguishable from controls relative to baseline, while TR-MDD individuals fail to show this increase in amygdala activity. Furthermore, the investigators have found that MDD participants (more generally, not specifically TR- MDD) are indeed able to increase their amygdala response during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that this increase is associated with large and rapid reductions in depressive symptoms. Here, the investigators propose to evaluate whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as an intervention for TR-MDD. 100 TR-MDD individuals will be randomly assigned under double-blind conditions to receive 5 amygdala rtfMRI-nf or 5 control rtfMRI-nf sessions where they are trained to regulate a parietal region putatively not involved in emotional processing or MDD. The investigators will assess changes in amygdala activity, severity of clinical symptoms, and autobiographical memory deficits. Success will suggest a new non- pharmacological, non-invasive intervention for a traditionally treatment-resistant population of MDD individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amygdala Neurofeedback | Experimental | Device: Amygdala Neurofeedbackattempt to up regulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Five sessions will be performed within a 2 month period. |
| Parietal Neurofeedback | Active comparator | Device: Parietal Neurofeedbackattempt to upregulate the left horizontal segment of the intraparietal sulcus, a region not involved in emotional processing, during positive autobiographical memory recall via real time fMRI neurofeedback. Five sessions will be performed within a 2 month period. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- right-handed adults (ages 18 - 55) with a primary diagnosis of MDD according to diagnostic criteria DSM-5 for recurrent MDD who are currently depressed will be recruited to participate
- must be able to give written informed consent prior to participation
- must have fewer than 45% memories categorized as specific on the Autobiographical Memory Test
- must have a SHAPS score > 4, indicating the presence of anhedonia
- unmedicated or stable on an SSRI antidepressant regime (at least 3 weeks to ensure symptoms are stable)
Key exclusion criteria (9 listed)
- have a clinically significant or unstable cardiovascular, pulmonary, endocrine, neurological, gastrointestinal illness or unstable medical disorder
- met DSM-IV criteria for alcohol and/or substance dependence (other than nicotine) within 12 months prior to screening
- have a history of traumatic brain injury
- are unable to complete MRI scan due to claustrophobia or general MRI exclusions (e.g., shrapnel inside body)
- are currently pregnant or breast feeding
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 |
|---|---|---|
| Amygdala NeurofeedbackParticipants are shown activity from their left amygdala in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories | Device | Amygdala Neurofeedback |
| Parietal NeurofeedbackParticipants are shown activity from their left horizontal segment of the intraparietal sulcus in real time and are instructed to increase the level of activity in that region by thinking of positive autobiographical memories | Device | Parietal Neurofeedback |
Primary outcome
Beck Depression Inventory (BDI-II)
Time frame: 12 weeks
1 secondary outcome
Amygdala Activity
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Background: PubMed 28407727Young KD, Siegle GJ, Zotev V, Phillips R, Misaki M, Yuan H, Drevets WC, Bodurka J. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall. Am J Psychiatry. 2017 Aug 1;174(8):748-755. doi: 10.1176/appi.ajp.2017.16060637. Epub 2017 Apr 14.
- Derived from this study: PubMed 38513424Compere L, Siegle GJ, Lazzaro S, Riley E, Strege M, Canovali G, Barb S, Huppert T, Young K. Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination. Behav Res Ther. 2024 May;176:104523. doi: 10.1016/j.brat.2024.104523. Epub 2024 Mar 15.
- Individual participant dataSharing planned: Undecided. The final data set will include self-reported demographic and behavioral data, clinical-rated information regarding illness course, severity, and comorbidities, and brain-imaging data collected during fMRI. The dataset will be stripped of identifiers prior to release for sharing, and will be shared openly and timely in accordance with the most recent NIH guidelines. Data will be shared every six months on the NIH-supported National Database for Clinical Trials Related to Mental Illness (NDCT) data repository.
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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.
Kymberly Young, 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 study testing Amygdala Neurofeedback and Parietal Neurofeedback in people with Treatment Resistant Depression, run by Kymberly Young 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 9 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 4 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Beck Depression Inventory (BDI-II) (time frame: 12 weeks). 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 NCT03428828, which also lists 2 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 4 Mar 2026.