Treatment Resistant Depression
Conditions
Keywords
transcranial magnetic stimulation, theta burst
Brief summary
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).
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.
Interventions
DEVICEActive 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).
DEVICEActive 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).
DEVICESham 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.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in MADRS Score | 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. |
| Percentage Change in SHAPS Score | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDavid Spiegel, MD
Stanford University
Participant flow
Recruitment details
Participants received treatment over a period of 1 week starting approximately 3 - 6 days after baseline, and had follow up assessments at 4 weeks and 8 weeks post treatment.
Pre-assignment details
Two participants who completed screening withdrew prior to assignment to a study arm.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants |
| Age, Continuous | 47.2 years STANDARD_DEVIATION 15.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 26.97 score on a scale STANDARD_DEVIATION 5.93 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 52 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 12 Participants |
| Snaith-Hamilton Pleasure Scale (SHAPS) | 9.19 score on a scale STANDARD_DEVIATION 2.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 22 |
| other Total, other adverse events | 0 / 23 | 0 / 23 | 0 / 22 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 22 |
Outcome results
None listed