Comparison of Anodal Transcranial Direct Current Stimulation (t-DCS) and Sham Stimulation in Patients With Treatment-resistant Depression
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
Study type: Interventional
Phase: Phase 4

Summary: 
      Major depressive disorder (MDD) is a significant public health problem. Existing treatment
      modalities are not always sufficient to alleviate this disorder. Treatment refractoriness is
      a common clinical problem. Transcranial direct current stimulation (t-DCS), a non-invasive
      brain stimulation technique, has been shown to be effective in alleviating depressive
      symptoms in preliminary studies. There is need to explore the role of t-DCS in
      Treatment-resistant depression (TRD). Therefore, the investigators aim to undertake this
      exploratory study.

      Aim:

      Compare the role of left prefrontal cortex anodal t-DCS daily stimulation of 4 weeks (20 week
      days) with sham stimulation in alleviating depressive symptoms in patients with TRD.

      Methodology: Patients who seek treatment in our treatment resistant depression clinic and who
      have failed to respond to treatment with two antidepressant medications will be offered to
      enroll in this study. The aim is to study 20 patients who meet the Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for MDD between the ages of 21-65
      years. Those subjects that receive sham stimulation will be offered to have active t-DCS
      stimulation for additional 3 weeks to get any benefit that they may have otherwise missed by
      being in the sham stimulation group.

      Results and Conclusions: The investigators will compare the mean baseline and end of
      treatment Montgomery Asberg depression rating scale between the two groups. The investigators
      will compare the change in mean depression scores between the baseline and end of treatment
      in those receiving active t-DCS for a total of 7 weeks duration. This study is innovative and
      of significance in exploring the role of this novel, easy to administer, safe and cost
      effective treatment modality.
    

Detailed description: 
      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.
    

Intervention name(s): Transcranial direct current stimulation (t-DCS); Sham Controlled Arm
Intervention type(s): Device; Other
Intervention description(s): The subjects randomized to this group will receive anodal t-DCS stimulation daily for four weeks. The stimulation parameters: current 2 mA continuously for 30 minutes.; The subjects randomized to this group will not receive stimulation daily for four weeks.
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment