Treatment Resistant Depression
Conditions
Keywords
transcranial magnetic stimulation, theta burst
Brief summary
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.
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 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, researchers have pursued modifying the treatment parameters to reduce treatment times with some preliminary successes. This study aims to further modify the parameters to create a more rapid form of the treatment and look at the change 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 stimulator.
DEVICESham TBS-DLPFC
The parameters in the active arms will be as above with the internal randomization of the device internally switching to sham in a blinded fashion.
DEVICEOpen label TBS-DLPFC
Patients will have the option of receiving active, open label aTBS treatment following sham. Stimulation will be delivered to the L-DLPFC using a MagPro stimulator or Nexstim TMS device.
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 22 to 80 years of age. * Able to provide informed consent. * Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE). * Participants may currently be on a stable and adequate dose of SSRI antidepressant therapy. Participants may choose to not be on antidepressant therapy for the study duration, or to be switched from other classes to a medication from the SSRI class. * Participants may also have a history of intolerance to at least 2 antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication. * Participants must qualify as Moderately Treatment Refractory or High Treatment Refractory using the Maudsley staging method. * Meet the threshold on the total HAMD17 score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * Meet the threshold on the total MADRS score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * Meet the threshold on the total BDI-II score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * In good general health, as ascertained by medical history. * If female, a status of non-childbearing potential or use of an acceptable form of birth control. The form of birth control will be documented at screening and baseline. * Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable.
Exclusion criteria
* Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. * Female that is pregnant or breastfeeding. * Female with a positive pregnancy test at participation. * Total HAMD17 score of \< 20 at the screen or baseline visits. * Total MADRS score of \< 20 at the screen or baseline visits. * Total BDI-II score of \< 20 at the screen or baseline visits. * Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence, at screening or within six months prior to screening. * Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more). * History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes. * Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening. * Considered at significant risk for suicide during the course of the study. * Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. * Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. * Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. * History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. * Current (or chronic) use of opiates. * History of epilepsy. * History of rTMS exposure. * History of any implanted device or psychosurgery for depression. * History of ECT intolerance. * History of shrapnel or metal in the head or skull. * Low Treatment Refractory using the Maudsley staging method. * History of cardiovascular disease or cardiac event. * History of OCD. * History of autism spectrum disorder. * History of intractable migraine * History of independent sleep disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from pre-treatment to 1-month post-treatment. | Pretreatment to 1-month posttreatment | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in the Columbia Suicide Severity Rating Scale (C-SSRS) | Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment | A suicidal ideation rating scale created by researchers at Columbia University. |
| Percentage change in the Hamilton Rating Scale for Depression (HAM-6) | Follow-up every 2 weeks for 6 months by telephone | A 6 item questionnaire used to score the severity of depression. |
| Percentage change in the Hamilton Rating Scale for Depression (HAMD-17) | 4 weeks posttreatment | A provider administered questionnaire used to assess remission and recovery from depression. |
| Change in baseline functional connectivity to 1-month post-treatment | Pretreatment to 1-month post-treatment | The investigators will assess functional connectivity as seen on resting state fMRI, between the subcallosal cingulate to the default mode network and within the default mode network. |
| Change in baseline heart rate variability through immediate post treatment and 1-month post treatment | Pretreatment, immediately posttreatment and 1-month post treatment | Heart rate variability measures will be compared baseline, immediate post treatment and 1-month post treatment |
| Change in baseline functional connectivity to immediate post-treatment using functional MRI | Pretreatment to immediately posttreatment | MR imaging of the brain to measure the functional connectivity between the subcallosal cingulate to the default mode network. |
Countries
United States
Outcome results
None listed