SAINT for Treatment of Preoperative Depression to Reduce Opioid Use Following Arthroplasty

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.