| Eligibility |
Inclusion Criteria:
1. women and men ages 18-80,
2. with MDD, of at least 12 weeks duration, according to Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5) criteria confirmed by the Mini
International Neuropsychiatric Interview (MINI; Sheehan et al, 1998),
3. have a Montgomery-Asberg Depression Rating Scale (MADRS - Montgomery and Asberg, 1979)
score of at least 20 at screen and baseline as assessed by site clinicians,
4. meet criteria for TRD during the current major depressive episode documented in the
MGH Antidepressant Treatment History Questionnaire (ATRQ) (Chandler et al., 2010),
which will be defined as being non-responders (less than 50% of symptom improvement)
to two or more depression treatment trials of adequate dose and duration as defined by
the MGH ATRQ,
5. are currently on an antidepressant of adequate dose (as defined by the MGH ATRQ) and
duration (at least 8 weeks), with the antidepressant dose being stable over the past
four weeks, and with documented (in the MGH ATRQ) non-response (less than 50%
improvement) to the current antidepressant.
6. Patients who have passed the MGH CTNI remote assessment, with documentation provided
to sites by MGH CTNI.
Exclusion Criteria:
1. pregnant or breastfeeding women, women of childbearing potential who are not using an
accepted means of birth control, or women with a positive urine pregnancy test,
2. patients who have received treatment with rTMS, aripiprazole, electroconvulsive
therapy (ECT), or venlafaxine during the current episode,
3. patients who express an objection to receiving treatment with at least one of the
three treatment arms of our study,
4. patients with any history of bipolar disorder or psychosis (diagnosed by MINI),
5. patients with active alcohol or substance abuse disorders within the past 6 months
(diagnosed by MINI),
6. patients with suicidal ideation of the degree that, in the opinion of the evaluating
clinician, participation in the study would place them at significantly increased risk
of suicide,
7. patients with unstable medical issues of such degree that, in the opinion of the
evaluating clinician, participation in the study would place them at significant risk
of a serious adverse event, or patients with a screening hemoglobin A1c level greater
than 7.5%, or patients with epilepsy, dementia, Parkinson's disease, or Huntington's
Disease,
8. patients who have received treatment with vagus nerve stimulation (VNS),
9. patients who have not responded to more than five FDA-approved antidepressant
treatment trials of adequate dose and duration during the current episode, or who did
not respond to ECT in previous episodes
10. patients on excluded medications,
11. patients with a positive urine screen drug test for a substance for which they do not
have a valid prescription for a valid medical reason,
12. patients with currently abnormal thyroid function tests,
13. patients who have received at least one dose of a monoamine oxidase inhibitor (MAOI)
four weeks or less prior, and
14. for patients on concomitant psychotropic agents (anticonvulsants, benzodiazepines,
hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone,
melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine,
lithium) not on the same dose for at least four weeks prior to study entry or who do
not agree to continue at the same dose during the acute phase of the study.
15. Patients who do not meet safety criteria for TMS: history of seizures, cardiac
pacemaker, DBS or VNS, brain aneurism clips or other metallic implants in the
intracranial space.
16. Also excluded is an individual who has received any administration of ketamine in the
current episode for the treatment of depression.
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