Home-Based Transcranial Direct Current Stimulation In Major Depressive Disorder (HOME)

Official title

Home-Based Transcranial Direct Current Stimulation in Major Depressive Disorder: a Multi-Centre, Two-Parallel Group, Superiority Randomised Controlled Trial

Overview

Depression is a prevalent and debilitating disorder. The most common treatments are antidepressant medications and talking therapies. However, for many individuals, these are not their treatment of choice. Furthermore, even following a full course of treatment with an antidepressant or talking therapy, over one third of patients continue to be unwell. The novel brain stimulation treatment, transcranial direct current stimulation (tDCS), is a potential first-line treatment for major depression. The present research question is whether home-based tDCS is an effective treatment for major depression for adults with major depression. Participants will be randomised to receive either a 10-week course of active tDCS treatment in addition to their standard care (Treatment as Usual), or to only receive Treatment as Usual. Participants will be followed up for 6-months after the start of the treatment began. After the 6-month follow-up visit, all participants from both groups can choose to continue/start the tDCS treatment. There will be a final follow-up visit 3 months later (9 months from the original treatment start of the trial).

Detailed description

Current pharmacotherapy and psychotherapy treatments for major depressive disorder (MDD) often fall short in efficacy and patient satisfaction, highlighting a critical need for innovative, effective and acceptable treatment options. Transcranial direct current stimulation (tDCS) has emerged as a promising treatment, offering a non-invasive method to modulate brain activity and alleviate depressive symptoms that can be provided at home.

This trial builds on our work and aims to evaluate the effectiveness and cost-effectiveness of home-based tDCS as a treatment for MDD in the NHS. The trial is a multi-centre pragmatic RCT to evaluate the real-life clinical effectiveness and cost-effectiveness of tDCS combined with treatment as usual (TAU) as compared to TAU alone following a 10-week treatment period and at a 6-month follow up. Depressive symptoms will be measured by the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS). We will further assess impact on self-report depressive symptoms, anxiety symptoms, remission, acceptability and quality of life. We will conduct in-depth process evaluation, economic evaluation, and implementation work to investigate operational challenges of integrating home-based tDCS into existing NHS care pathways and to inform scalability in primary care settings.

438 Participants will be aged 18 years or over, diagnosed with MDD with at least moderate severity of depressive symptoms and medication free or taking stable antidepressant medication or in psychotherapy for at least 6 weeks before enrolment. Participants will be randomly assigned in a 1:1 ratio to either TAU or TAU+tDCS.

Participants randomised to the TAU treatment arm will continue with standard care including psychotherapy and/or antidepressant medication, as decided by participant and treating clinician. Participants randomised to the tDCS treatment arm will use a tDCS device which is a headset with the anode positioned over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC (EEG positions F3 and F4, respectively). Treatment protocol consists of 5 tDCS sessions per week for 3 weeks followed by 3 tDCS sessions per week for 7 weeks, for a total of 36 sessions in 10 weeks. tDCS stimulation is 2 mA for 30 minutes with gradual ramp up over 30 seconds at the start and end of each session.

The primary outcome is the difference in depressive symptoms between treatment arms at 10-week end of treatment as measured by MADRS and the key secondary outcome is the long term clinical effectiveness as measured by difference in depressive symptoms between treatment arms at 6-month follow up as measured by MADRS.

After the 6-month follow up, a 3-month extension follow up phase will give all participants the opportunity to use the tDCS device.

This research addresses an unmet need for new treatment options for MDD, thereby benefiting people with MDD, improving NHS care pathways, and expanding scientific knowledge.

Interventions

• Device transcranial direct current stimulation (tDCS)
  Participants randomised to the tDCS treatment arm will use a tDCS device which is a headset with the anode positioned over left dorsolateral prefrontal cortex (DLPFC) and cathode over right DLPFC (EEG positions F3 and F4, respectively). Treatment protocol consists of 5 tDCS sessions per week for 3 weeks followed by 3 tDCS sessions per week for 7 weeks, for a total of 36 sessions in 10 weeks. tDCS stimulation is 2 mA for 30 minutes with gradual ramp up over 30 seconds at the start and end of each

Primary outcome measures

• Montgomery-Åsberg Depression Rating Scale (MADRS) [Time frame: 10 weeks]

Secondary outcome measures (11)

• Montgomery-Åsberg Depression Rating Scale (MADRS) [Time frame: 6 months]
• Hamilton Depression Rating Scale (HDRS) [Time frame: 10 weeks]
• Hamilton Anxiety Rating Scale (HAMA) [Time frame: 10 weeks]
• Montgomery-Åsberg Depression Rating Scale-Self Report (MADRS-S) [Time frame: 10 weeks]
• Hamilton Depression Rating Scale (HDRS) [Time frame: 6 months]
• Hamilton Anxiety Rating Scale (HAMA) [Time frame: 6 months]
• Montgomery-Åsberg Depression Rating Scale-Self Report (MADRS-S) [Time frame: 6 months]
• Montgomery-Åsberg Depression Rating Scale (MADRS) clinical response [Time frame: 10 weeks]
• Montgomery-Åsberg Depression Rating Scale (MADRS) treatment remission [Time frame: 10 weeks]
• Montgomery-Åsberg Depression Rating Scale (MADRS) clinical response [Time frame: 6 months]
• Montgomery-Åsberg Depression Rating Scale (MADRS) treatment remission [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Adults aged 18 years or over
• Current episode of depression based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (APA, 2013) for major depressive disorder (MDD) as assessed by structured clinical assessment, Mini-International Neuropsychiatric Interview (MINI) (Sheehan et al., 1998)
• Having at least a moderate severity of depressive symptoms as measured by a score of at least 18 in MADRS
• Either not taking antidepressant medication or taking a stable dose of antidepressant medication for at least 6 weeks before enrolment.
• Either not currently in psychotherapy or in ongoing psychotherapy for at least 6 weeks before enrolment.
• Being under the care of GP
• Agreeable for GP to be regularly informed about study participation
• Able to provide written, informed consent

Exclusion criteria

• Significant suicide risk as measured by answering 'yes' to questions 4, 5 or 6 on the Columbia Suicide Severity Rating Scale (C-SSRS) Screen (Posner et al., 2011)
• Primary comorbid psychiatric disorder (e.g. obsessive compulsive disorder) based on DSM-5 criteria as assessed in MINI
• Current daily use of medications that affect cortical excitability (e.g. benzodiazepines)
• Current illicit drug use or heavy alcohol use with high risk of alcohol use disorder as measured by a score of 8 or more in Alcohol use disorders identification test consumption (AUDIT C) (Khadjesari et al., 2017; NICE, 2023)
• History of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain stimulation
• History of esketamine / ketamine for treatment of depression
• History of psychosurgery for depression
• Having cognitive impairment (e.g. dementia)
• Current medical disorder or neurological disorder that may mimic mood disorder (e.g. hormonal disorder, unstable heart disease)
• Have any implant in the brain or neurocranial defect
• Have shrapnel or any ferromagnetic material in the head
• Have any active implantable medical device (e.g. pacemaker)
• If female and of child-bearing potential, currently pregnant or planning to become pregnant during the study
• Concurrent enrolment in another interventional study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United Kingdom · 6 centers

• Cardiff and Vale Health Board — Cardiff
• South London and Maudsley NHS Foundation Trust — London
• Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust — Newcastle
• Northamptonshire Healthcare NHS Foundation Trust — Northampton
• Nottinghamshire Healthcare NHS Foundation Trust — Nottingham
• Hampshire and Isle of Wight Healthcare NHS Foundation Trust — Southampton

Identifiers

NCT: NCT07228468 · NIHR165425 · NIHR165425

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗