Home-based transcranial direct current stimulation in major depressive disorder: a multi-centre, two-parallel group, superiority randomised controlled trial

Research question: What is the clinical effectiveness and cost-effectiveness of home-based tDCS treatment for major depressive disorder (MDD)? Background: Major depressive disorder (MDD) is a prevalent and debilitating mental health disorder, significantly exacerbated by the Covid-19 pandemic, particularly in women, younger adults, and individuals in deprived areas. While pharmacotherapy and psychotherapy are first-line treatments, their limitations in efficacy, tolerability, and acceptability necessitate additional treatment options. This need is strongly endorsed by our patient and public involvement group. Aims and Objectives: Aims are to assess the clinical effectiveness, cost-effectiveness and NHS implementation of home-based transcranial direct current stimulation (tDCS) treatment for MDD. The primary objective is to evaluate clinical effectiveness as the difference in depressive symptoms at 10-week end of treatment between the two treatment arms: those receiving treatment as usual (TAU) alone and those receiving TAU plus tDCS (TAU+tDCS), as measured by clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS). Key secondary objective is to evaluate sustained clinical effectiveness as the difference in depressive symptoms at 6 months between the treatment arms as measured by MADRS. Additional secondary objectives include effectiveness on self-reported mood, anxiety and quality of life at end of treatment and longer term at 6 months and cost-effectiveness analysis. Process evaluation will assess adherence, safety and fidelity, and implementation will explore scalability and integration within NHS care pathways. Methods: Multi-centre, pragmatic, two-parallel group, superiority randomised controlled trial (RCT) will include 438 participants diagnosed with MDD based on DSM-5 criteria by structured clinical interview. Inclusion criteria include first episode MDD to recurrent MDD and treatment resistant depression as defined by lack of response to two or more previous treatments. Participants will be randomly assigned to receive either TAU or TAU+tDCS. tDCS device is headset with anode positioned over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC (EEG positions F3 and F4). Treatment consists of 5 tDCS sessions per week for 3 weeks then 3 tDCS sessions per week for 7 weeks in addition to TAU, for a total of 36 sessions in 10 weeks. tDCS stimulation is 2 mA for 30 minutes per session. TAU standard care consists of psychotherapy and/or antidepressant medication. Timelines for delivery: With our implementation toolkit, we expect that this treatment option will be available in day-to-day care within 5 years. Anticipated impact and dissemination: This research addresses an unmet need for more treatment options for MDD, which will benefit individuals with MDD and improve NHS care pathways. This research addresses the NHS Long Term Plan for NHS service models to boost 'out-of-hospital' and to personalise care for MDD. Dissemination will be through academic publications, social media, stakeholder events, and implementation toolkit.