Treatment Resistant DepressionNCT03680781
Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study
A study testing Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC and Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC in people with Treatment Resistant Depression, run by Stanford University at 1 site in United States.
Trial summary
This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC and Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Apr 2018to 2 Dec 2024
- Phase
- Interventional
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, 18 to 75 years of age.
- Able to provide informed consent.
- Diagnosed with Major Depressive Disorder (MDD) or bipolar affective disorder 2 and currently experiencing a Major Depressive Episode (MDE).
- prior exposure to rTMS
- Participants must qualify as "moderate or severe treatment refractory" using the Maudsley staging method.
- Participants may continue antidepressant regimen, but must be stable for 6 weeks prior to enrollment in the study. They must maintain that same antidepressant regimen throughout the study duration.
- Participants are required to have a stable psychiatrist for the duration of study enrollment.
Who cannot join
- History of MI, CABG, CHF, or other cardiac history
- Any neurological conditions
- History of epilepsy
- OCD
- Independent sleep disorder
- Autism Spectrum Disorder
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine
Palo Alto, California, 94305
About this study
This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.
Read the detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as 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 very successful. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will investigate the efficacy of a further modified protocol, creating a more rapid form of the treatment and look at the change in neuroimaging biomarkers. In particular, this study will determine the efficacy of re-treatment in individuals who have already experienced benefit of the accelerated protocol to ensure results can be repeated.
- Conditions
- Treatment Resistant Depression
- Being tested
- Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC, Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFCDevice
Participants will receive iTBS to the left DLPFC and will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField 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 or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.
Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFCDevice
Participants will receive iTBS to bilateral DLPFC. The DLPFC will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField 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 or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.
| Study group | Role | What they receive |
|---|---|---|
| Accelerated theta burst treatment | Experimental | All participants will receive theta-burst TMS. Receives: Device: Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC; Device: Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton Depression Rating Scale 21-Item Score
A 21 item clinical assessment tool used to rate a patient's level of depression. The total scores range from 0 to 63 with higher scores indicating worse depression.
Measured: Difference between baseline and follow up at one month after the final aiTBS treatment (on day 5)
Secondary outcomes (7)
Change in Hamilton Rating Scale for Depression (HAMD-17)
The HAMD-17 is a 17-item rating scale questionnaire administered by clinicians to rate a patient's level of depression . The total scores range from 0 to 52 with higher scores indicating worse depression.
Measured: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in The Scale for Suicide Ideation
A rating scale that measures the current intensity of specific attitudes, behaviors, and plans to commit suicide. The total scores range from 0 to 38 with higher scores indicating greater suicidality.
Measured: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in Hamilton Rating Scale for Depression (HAMD-6)
The HAMD-6 is a shorter, six-item version of the Hamilton Depression Rating Scale (HAMD-D) that measures core symptoms of major depressive disorder, such as depressed mood, guilt and anxiety. The total scores range from 0 to 22 with higher scores indicating worse depression.
Measured: Every day of stimulation on days (visits) 1, 2, 3, 4, and 5
Change From Baseline Functional Connectivity Within the Default Mode Network.
We will assess functional connectivity as seen on resting state fMRI within the default mode network.
Measured: Baseline, immediately post-treatment, 4 weeks post-treatment
Change From Baseline Functional Connectivity of Subcallosal Cingulate Cortex and the Default Mode Network.
We will assess functional connectivity as seen on resting state fMRI of subcallosal cingulate cortex to the default mode network.
Measured: Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Beck Depression Inventory (BDI)
The Beck Depression Inventory (BDI) is a 21-item self-report questionnaire used to measure the severity of depression symptoms. The total scores range from 0 to 63 with higher scores indicating worse depression.
Measured: Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
The MADRS (Montgomery-Åsberg Depression Rating Scale) is a 10-item diagnostic tool used by clinicians to assess the severity of depression by scoring symptoms on a 0-60 scale with higher scores indicating worse depression.
Measured: Baseline, immediate post-treatment, 4 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start13 Apr 2018
- Primary completion2 Dec 2024
- Study completion2 Dec 2024
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 (6)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gregory Sahlem, Stanford University
- Investigators
- Gregory Sahlem, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03680781
- Sponsor's protocol ID
- IRB-44150
- Status last verified
- Jun 2026
- First submitted
- 10 Sep 2018
- Last updated
- 22 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
PubMed 20439832George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
PubMed 8547583Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
PubMed 8684201Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.
PubMed 26850210Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.
PubMed 25281475Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.
PubMed 25450537
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study
- ClinicalTrials.gov ID
- NCT03680781
- Acronym / sponsor ID
- IRB-44150
- Conditions
- Treatment Resistant Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 13 Apr 2018 (actual)
- Primary completion
- 2 Dec 2024 (actual)
- Study completion
- 2 Dec 2024 (actual)
- First posted
- 21 Sep 2018 (actual)
- Results
- Posted 21 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.
Detailed description
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as 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 very successful. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will investigate the efficacy of a further modified protocol, creating a more rapid form of the treatment and look at the change in neuroimaging biomarkers. In particular, this study will determine the efficacy of re-treatment in individuals who have already experienced benefit of the accelerated protocol to ensure results can be repeated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Accelerated theta burst treatment | Experimental | Device: Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC, Device: Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFCAll participants will receive theta-burst TMS. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, 18 to 75 years of age.
- Able to provide informed consent.
- Diagnosed with Major Depressive Disorder (MDD) or bipolar affective disorder 2 and currently experiencing a Major Depressive Episode (MDE).
- prior exposure to rTMS
- Participants must qualify as "moderate or severe treatment refractory" using the Maudsley staging method.
Key exclusion criteria (6 listed)
- History of MI, CABG, CHF, or other cardiac history
- Any neurological conditions
- History of epilepsy
- OCD
- Independent sleep disorder
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 |
|---|---|---|
| Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFCParticipants will receive iTBS to the left DLPFC and will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField 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 or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device. | Device | Accelerated theta burst treatment |
| Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFCParticipants will receive iTBS to bilateral DLPFC. The DLPFC will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField 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 or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device. | Device | Accelerated theta burst treatment |
Primary outcome
Change in Hamilton Depression Rating Scale 21-Item Score
Time frame: Difference between baseline and follow up at one month after the final aiTBS treatment (on day 5)
A 21 item clinical assessment tool used to rate a patient's level of depression. The total scores range from 0 to 63 with higher scores indicating worse depression.
7 secondary outcomes
Change in Hamilton Rating Scale for Depression (HAMD-17)
Time frame: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in The Scale for Suicide Ideation
Time frame: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in Hamilton Rating Scale for Depression (HAMD-6)
Time frame: Every day of stimulation on days (visits) 1, 2, 3, 4, and 5
Change From Baseline Functional Connectivity Within the Default Mode Network.
Time frame: Baseline, immediately post-treatment, 4 weeks post-treatment
Change From Baseline Functional Connectivity of Subcallosal Cingulate Cortex and the Default Mode Network.
Time frame: Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Beck Depression Inventory (BDI)
Time frame: Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: Baseline, immediate post-treatment, 4 weeks post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20439832George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
- Background: PubMed 8547583George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
- Background: PubMed 8684201Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
- Background: PubMed 26850210Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.
- Background: PubMed 25281475Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.
- Background: PubMed 25450537Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.
- Individual participant dataSharing planned: No
Related trials for Treatment Resistant Depression
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression
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.
Gregory Sahlem, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC and Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC in people with Treatment Resistant Depression, run by Stanford University 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 7 inclusion and 6 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 22 Jul 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?
Yes. Results are posted in the registry (first posted 21 Apr 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?
Change in Hamilton Depression Rating Scale 21-Item Score (time frame: Difference between baseline and follow up at one month after the final aiTBS treatment (on day 5)). 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 NCT03680781, which also lists 6 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 22 Jul 2026.