Spinal Cord Stimulation for the Treatment of Major Depressive Disorder

This study aims to 1) determine the efficacy and safety of tsDCS in adult patients with MDD
and 2) investigate interoceptive awareness, somatic symptoms, autonomic and metabolic
regulation as potential mediators of antidepressant response to tsDCS. We predict that 1)
Active tsDCS treatment will result in a greater decrease in depressive symptom severity
compared to Sham tsDCS in adult patients with MDD, 2) active tsDCS will be safe and well
tolerated in adult patients with MDD and 3) change in interoceptive awareness, somatic
symptoms, and autonomic and metabolic parameters will be associated with change in depressive
symptom severity. To accomplish these aims, we will conduct an 8-week, double blinded,
randomized, sham controlled, parallel group, pilot clinical trial study design. A total of 20
adult antidepressant-free MDD patients will be randomized to receive Active (n=10) or Sham
(n=10) tsDCS protocols for 8 weeks in a 1:1 ratio. We will combine the use of a tsDCS device,
psychometric instruments to diagnose MDD, and measures of depressive symptom severity,
somatic symptoms, interoceptive awareness, autonomic function (blood pressure, heart rate),
and potential metabolic markers as predictors of response.

Inclusion criteria:

1. age 18-55 yrs., inclusive

2. female or male

3. BMI 18.5 to 35 kg/mts2, inclusive

4. current MDD episode diagnoses confirmed by Mini International Neuropsychiatric
Interview (MINI) 5.0 with a duration of ≥1 month and ≤24 months

5. moderate MDD symptoms according to Montgomery-Asberg Depression Rating Scale (MADRS)
score ≥ 20 to ≤35

6. no current or recent (past month) antidepressant pharmacological treatment

7. GAD and other anxiety symptoms will be permitted

8. using an effective contraceptive method (all participants of childbearing potential).

Exclusion criteria:

1. Current or lifetime MDD episode non-responsive to two or more antidepressant
treatments at adequate doses and time (including ECT)

2. Current or lifetime bipolar disorder or schizophrenia diagnosis

3. current (past month): PTSD, psychotic or substance use disorder (nicotine and caffeine
allowed)

4. significant risk of suicide according to CSSRS or clinical judgment, or suicidal
behavior in the past year

5. current chronic severe pain conditions

6. current chronic use of: opioids analgesics, medications that affect blood pressure or
drugs with significant autonomic effects (stimulants and antipsychotics allowed if
dose stable for 1 month)

7. neurological, endocrinological, cardiovascular (including diagnosed hypertension) or
other clinically significant medical conditions as judged by the clinician

8. skin lesions on electrode placement region

9. implanted electrical medical devices

10. Pregnancy

11. suspected IQ<80

12. any other clinically relevant reason as judged by the clinician.