Dose-Optimized and Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. People between the ages of 18 and 85 at the time of screening.

2. Able to read, understand, and provide written, dated informed consent prior toscreening. Proficiency in English sufficient to complete questionnaires / followinstructions during interventions. Stated willingness to comply with all studyprocedures, including availability for the duration of the study, and to communicatewith study personnel about adverse events and other clinically importantinformation.

3. Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for aMajor Depressive Episode, according to the criteria defined in the Diagnosis andStatistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).

4. Medical records confirming a history of at least moderate treatment-resistance asdefined an Antidepressant Treatment History Form (ATHF) score for thatantidepressant trial of > 2 in the current episode OR have been unable to tolerateat least 2 separate trials of antidepressants of inadequate dose and duration (ATHFscore of 1 or 2 on those 2 separate antidepressants) OR have a combination of onefailed trial and one not tolerated trial, per the definitions above.

5. MADRS score of ≥20 at screening (Visit 1).

6. Existing relationship with mental health provider and access to ongoing psychiatriccare before and after completion of the study.

7. Must be on a stable antidepressant therapeutic regimen, or not receiving treatmentfor 4 weeks prior to study enrollment and agree to continue this regimen throughoutthe study period.

8. In good general health, as evidenced by medical history.

9. For persons of child-bearing potential: use of highly effective contraception for atleast 1 month prior to screening and agreement to use such a method during studyparticipation.

10. Agreement to adhere to Lifestyle Considerations (i.e. must continue with anyexisting treatments) throughout study duration.

11. For persons of child-bearing potential: must take a pregnancy test at the screeningvisit, with results confirmed as negative by study staff.

Exclusion Criteria:

An individual will be excluded from participation in this study if they meet any of the following criteria, as determined from a review of medical records prior to screening or at the screening visit:

1. Pregnancy;

2. History of psychotic or bipolar disorder or depression with psychotic features;

3. Significant borderline personality disorder;

4. Significant comorbid obsessive-compulsive or post-traumatic stress disorder;

5. Previously diagnosed Intellectual Disability or Autism Spectrum Disorder;

6. Current moderate or severe substance use disorder or demonstrating signs of acutesubstance withdrawal;

7. Clinically significant suicidality;

8. Any history of tDCS;

9. Any history of ECT;

10. History of TMS (greater than 15 sessions) without a clinically meaningful response.

11. History of ketamine (greater than 4 sessions) without a clinically meaningfulresponse;

12. Chronic depression (defined as of over 5 years duration);

13. History of significant neurologic disease, including dementia, Parkinson's orHuntington's disease, brain tumor, seizure disorder, subdural hematoma, multiplesclerosis, or history of significant head trauma with persistent symptoms;

14. Untreated or insufficiently treated endocrine disorder;

15. Contraindication to receiving tDCS (e.g., ferromagnetic implant, history of seizure,known brain lesion);

16. Treatment with an investigational drug or other intervention within the studyperiod;

17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change inMADRS score;

18. Require a benzodiazepine with a dose > lorazepam 2 mg/day

19. Has started a new psychotherapeutic process in the past 3 months from screening;

20. Use of potentially irritant topical treatments (ex: retinoids, alpha hydroxy acids)

21. Aesthetic procedure the area of the forehead directly below the stimulation areawithin the last 6 months (laser, fillers, surgery, etc.)

22. Any active dermatological condition on face or scalp that would in the opinion ofthe PI represent a contraindication to the treatment.