Noninvasive brain stimulation for treating anhedonic depression

Individualized Neuromodulation for Anhedonic Depression

Not applicable Interventional University of California, San Diego · NCT05537285

This study is testing different types of brain stimulation to see if they can help people with anhedonic depression feel better compared to a placebo treatment.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment129 (estimated)
Ages18 Years to 80 Years
SexAll
SponsorUniversity of California, San Diego Academic / other
Locations1 site (San Diego, California)
Trial IDNCT05537285 on ClinicalTrials.gov

What this trial studies

This research involves a three-arm, randomized, placebo-controlled trial that tests noninvasive brain stimulation techniques for patients suffering from anhedonic depression. Participants will be recruited at UCSD and randomized to receive either individualized or standard forms of accelerated intermittent theta burst stimulation, or a sham treatment. The study aims to compare the effectiveness of these interventions and develop brain-behavior biomarkers to better identify suitable treatment options for anhedonic depression. Additionally, the research seeks to phenotype anhedonic depression based on the collected data.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 diagnosed with Major Depressive Disorder or Bipolar Disorder type II, experiencing moderate to severe treatment-resistant depression.

Not a fit: Patients who do not meet the criteria for Major Depressive Disorder or those with other forms of depression may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a novel treatment option for patients with anhedonic depression, potentially improving their quality of life.

How similar studies have performed: Other studies utilizing noninvasive brain stimulation techniques have shown promise, suggesting potential success for this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Male or Female, between the ages of 18 and 80 at the time of screening.
* Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
* Currently diagnosed with Major Depressive Disorder (MDD) or Bipolar Disorder type II and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
* Medical records confirming a history of moderate to severe treatment-resistance as defined an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
* MADRS score of ≥20 at screening (Visit 1).
* Access to ongoing psychiatric care before and after completion of the study.
* Access to open label neuromodulation treatment after study completion.
* Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
* In good general health, as evidenced by medical history.
* For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
* Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

* Pregnancy
* History of or current psychotic disorder or depression with psychotic features
* Severe borderline personality disorder.
* Diagnosis of Intellectual Disability or Autism Spectrum Disorder
* Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
* Urine screening test positive for illicit substances
* Clinically significant suicidal ideation with plan
* Any history of ECT (greater than 8 sessions) without a clinical meaningful response.
* Recent (during the current depressive episode) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days
* History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
* Untreated or insufficiently treated endocrine disorder.
* Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
* Contraindication to MRI (ferromagnetic metal in their body)
* Treatment with an investigational drug or other intervention within the study period
* Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
* Require a benzodiazepine with a dose \> lorazepam 2 mg/day or equivalent or any anticonvulsant.

Where this trial is running

San Diego, California

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions MDDAnhedonia
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.