Home-Based Randomized Trial of Spaced Transcranial Direct Current Stimulation for Treatment-Resistant Depression

Inclusion Criteria: * People between the ages of 18 and 70 at the time of screening. * Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information. * Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5). * Medical records confirming a history of at least moderate treatment-resistance as defined on Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of \> 2 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above. * MADRS score of ≥20 at screening. * Existing relationship with mental health provider and access to ongoing psychiatric care before and after completion of the study. * Must be on a stable antidepressant therapeutic regimen for at least 4 weeks prior to study enrollment and agree to continue this regimen throughout the study period. Participants who are not currently on antidepressant treatment are eligible, provided that no discontinuation occurred within the 4 weeks preceding study enrollment. * For persons of child-bearing potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation. * Agreement to adhere to Lifestyle Considerations (i.e. must continue with any existing treatments) throughout study duration. * For persons of childbearing potential: must take a pregnancy test prior to initiating treatment, with results confirmed as negative by study staff * Participants will need to have a stable internet connection and a device compatible with UCSD Microsoft Teams or UCSD Zoom to facilitate remote communication and engagement in study activities. Exclusion Criteria: * Pregnancy this includes breastfeeding or trying to becoming pregnant. * History of psychotic or bipolar disorder or depression with psychotic features. * Significant borderline personality disorder. * Significant comorbid obsessive-compulsive or post-traumatic stress disorder. * Previously diagnosed Intellectual Disability or Autism Spectrum Disorder. * Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal. * Clinically significant suicidality. * Any history of tDCS. * Any history of ECT. * History of TMS (greater than 15 sessions) without a clinically meaningful response. * History of ketamine (greater than 4 sessions) without a clinically meaningful response. * History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma with persistent symptoms. * Untreated or insufficiently treated endocrine disorder. * Contraindication to receiving tDCS (e.g., ferromagnetic implant, history of seizure, known brain lesion). * Treatment with an investigational drug or other intervention within the study period. * Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score. * Require a benzodiazepine with a dose \> lorazepam 2 mg/day * Has started a new psychotherapeutic process in the past 3 months from screening. * Use of potentially irritant topical treatments (ex: retinoids, alpha hydroxy acids).