Personalized Therapeutic Neuromodulation for Anhedonic Depression

July 1, 2026 updated by: David Spiegel, Stanford University
This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been effective in real world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session, 5 days per week, for 4-8 weeks). Recently, the investigators have pursued modifying the treatment parameters to reduce treatment times with an accelerated treatment paradigm. This study aims to further study the accelerated protocol and examine changes in neuroimaging biomarkers.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

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
    • California
      • Stanford, California, United States, 94305
        • Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

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

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or Female, between the ages of 18 and 80 at the time of screening.
  2. 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.
  3. Currently diagnosed with Major Depressive Disorder (MDD)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).
  4. The patient has demonstrated a failure of one or more trials of a pharmacological medication as treatment for MDD.
  5. MADRS score of ≥20 at screening (Visit 1).
  6. TMS naive.
  7. Access to ongoing psychiatric care before and after completion of the study.
  8. 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.
  9. In good general health, as evidenced by medical history.
  10. 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.
  11. Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

  1. Pregnancy
  2. History of or current psychotic disorder or bipolar disorder
  3. Severe borderline personality disorder
  4. Diagnosis of Intellectual Disability or Autism Spectrum Disorder
  5. Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder
  6. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
  7. Urine screening test positive for illicit substances
  8. Acute suicide risk based on clinical judgement or a suicide attempt within the past 6 months
  9. Any history of ECT (greater than 8 sessions) without meeting responder criteria
  10. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT)
  11. 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
  12. Untreated or insufficiently treated endocrine disorder.
  13. Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
  14. Contraindication to MRI (ferromagnetic metal in their body)
  15. Treatment with an investigational drug or other intervention within the study period
  16. Depth-adjusted aiTBS treatment dose > 65% maximum stimulator output (MSO)
  17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
  18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active TBS-DLPFC
The active group will receive theta-burst TMS stimulation.
Device: Active TBS-DLPFC

Participants in the active stimulation group will receive intermittent TBS to left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004).

Stimulation will be delivered to the L-DLPFC using a MagPro TMS system (MagVenture, Denmark).
Active Comparator: Active TBS-DMPFC
The active group will receive theta-burst TMS stimulation.
Device: Active TBS-DMPFC

Participants in the active stimulation group will receive intermittent TBS to DMPFC. The DMPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004).

Stimulation will be delivered to the DMPFC using a MagPro TMS system (MagVenture, Denmark).
Sham Comparator: Sham Comparator: Sham TBS-DLPFC or DMPFC
The sham group will receive sham theta-burst TMS stimulation.
Device: Sham TBS-DLPFC or DMPFC
The parameters in the sham arm will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage Change in MADRS Score
Time Frame: Baseline, immediate post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment.
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item self-survey administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Score range: 0 to 54, higher scores correspond to more severe depressive symptoms.
Baseline, immediate post treatment (up to 2 weeks post baseline), 4 weeks and 8 weeks post treatment.
Percentage Change in SHAPS Score
Time Frame: Baseline, immediate post treatment (up to 2 weeks post baseline), 4 week and 8 week post treatment.
The Snaith-Hamilton Pleasure Scale is a 14-item self-report questionnaire designed to measure the reduced ability to experience pleasure. Score range: 0 to 14, higher scores indicate higher levels of anhedonia.
Baseline, immediate post treatment (up to 2 weeks post baseline), 4 week and 8 week post treatment.

Collaborators and Investigators

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

Sponsor

Stanford University

Investigators

  • Principal Investigator: David Spiegel, MD, Stanford University

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)

May 31, 2022

Primary Completion (Actual)

June 6, 2025

Study Completion (Actual)

December 31, 2025

Study Registration Dates

First Submitted

November 16, 2021

First Submitted That Met QC Criteria

November 30, 2021

First Posted (Actual)

December 3, 2021

Study Record Updates

Last Update Posted (Actual)

July 29, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 63771

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

No

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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