Comparison of Anodal Transcranial Direct Current Stimulation (t-DCS) and Sham Stimulation in Patients With Treatment-resistant Depression

Research Plan: 1. Patients who score \>10 on our intake screening questionnaire, the patient Health Questionnaire (PHQ-9) will be advised to call to seek participation in this study. 2. Patients who seek treatment in our treatment resistant depression clinic will be offered to enroll in this study. 3. Patients who have failed to respond to at least two antidepressants in adequate dosage for at least 4 weeks. 4. The aim is to have 20 patients complete the study by enrolling 24 patients and screening another 26 patients who meet the diagnostic and statistical manual, DSM-IV criteria for Major depressive disorder, MDD and have failed treatment with at least two antidepressant medications. 5. Patients will be interviewed by investigators to see if they meet the eligibility for inclusion in the study. The evaluation will consist a medical and psychiatric evaluation if not done in last one year and a monthly urine pregnancy test for women of child bearing potential. If the subjects do not meet the eligibility criteria they will continue to receive routine clinical care or referral for appropriate psychiatric care within or outside of our clinic/department 6. Stimulation parameters: Left prefrontal anodal t-DCS stimulation daily for four weeks. The stimulation parameters: current 2 mA continuously for 30 minutes. Conductive electrodes covered by sponge soaked in saline will be used. The current will gradually be increased to 2mA over 30 seconds to avoid sensation of a flash. 7. Patients will be allotted to receive either active or sham stimulation by using a random numbers assignment (www.randomizer.org). Co-investigator Dr. Holbert will be doing the assessments rating the depressive symptoms and he kept blind as to the type of stimulation received. The same machine will be used to give both active and sham stimulation. 8. At the end of four weeks subjects will be offered to stay in open label extension of this study with active left prefrontal anodal t-DCS for another three weeks to receive any benefits they may otherwise not receive by being in sham stimulation. 9. Materials: Montgomery Asberg depression rating scale, MADRS, Patient Health Questionnaire, PHQ-9, Clinical Global Impression(CGI) at baseline and weekly. Improvement will be considered as 50 % reduction in depressive scores and remission as a score of less than 9 on MADRS. MADRS is a 10 item examiner rated scale that rates various depressive signs and symptoms and has been used extensively in research of brain stimulation techniques.PHQ-9 is a 9 item self-rated questionnaire about depressive symptoms and has been found reliable in studies of depression in primary care and psychiatric settings. CGI is a clinician rated impression about treatment response. Procedure outline: Baseline: diagnostic interview, evaluation of inclusion and exclusion criteria, urine pregnancy test if indicated at baseline and day 31, filling in questionnaires: PHQ-9, MADRS, CGI Daily: t-DCS stimulation for 30 minutes; patients will be asked about any discomfort/side effects. Days: 7,14,21,28,35,42,49: PHQ-9, MADRS, CGI Specifically, the investigators will compare baseline to post treatment depression scores via a two-sample t-test, comparing active treatment to sham using a two-sided P-value \<0.05 to declare significance. The change in MADRS score (MADRS) will be the primary outcome variables. Secondary variables will be analyzed similarly in this pilot study. Significant findings on secondary variables will not be considered as definitive.