Remote, home-based tDCS shows modest symptom relief and higher remission in major depression, with generally good safety but burn risks to watch.
TRANSLATING RESEARCH INTO PRACTICE
Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP, Column Editor
A monthly column dedicated to reviewing the literature and sharing clinical implications.
Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates cortical excitability, particularly in the dorsolateral prefrontal cortex (DLPFC). This treatment has been studied as a potential treatment for several psychiatric disorders, including major depressive disorder (MDD). Most prior studies of tDCS efficacy and safety have involved daily visits to a clinic. However, tDCS devices are portable, which has spurred recent interest in home-based care delivery. Woodham et al sought to explore the possibility of MDD treatment with tDCS outside of the traditional clinical setting. This approach could improve access to care, particularly for patients who face barriers to frequent in-person visits.
Woodham RD, Selvaraj S, Lajmi N, et al.
The study was funded by Flow Neuroscience, the National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Substance Abuse and Mental Health Services Administration, the Baszucki Brain Research Fund (Milken Institute), the Rosetrees Trust, the International Psychoanalytical Association, the Medical Research Council (UK), the Brain & Behavior Research Foundation, the Wellcome Trust, the National Institute for Health and Care Research Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London, and the Pfizer Foundation. Notably, since the publication of this study, Flow Neuroscience has obtained FDA clearance for its home-based tDCS device.
To evaluate whether 10 weeks of home-based, remotely supervised tDCS treatment is superior to sham stimulation for adults currently experiencing depressive symptoms with MDD.
This double-blind, sham-controlled, phase 2 randomized trial was conducted at multiple sites in England, Wales, and Texas. Participants were adults with MDD with a current depressive episode of at least moderate severity as determined by a structured diagnostic interview. Exclusion criteria included a history of mania or psychosis, high risk of suicide, history of hospital admission for suicidality, history of poor response to 2 or more treatments, starting antidepressant medication within less than 6 weeks before screening, and active substance abuse. Participants were randomly assigned 1:1 to active tDCS or sham tDCS treatment arms. Active stimulation was delivered at 2 mA for 30 minutes per session using a bifrontal montage (anode over left DLPFC, cathode over right DLPFC), while the sham used 0 mA with brief ramp-up/ramp-down periods to mimic the sensation of active stimulation.
The treatment protocol consisted of 5 sessions per week for the first 3 weeks, followed by 3 sessions per week for the remaining 7 weeks, for a total of 10 weeks in the blinded phase. This was followed by a 10-week open-label phase in which all participants received active tDCS (outcomes from this phase were not reported in this paper). The primary outcome studied was the change in depressive symptoms measured by the Hamilton Depression Rating Scale (HAM-D). Secondary outcomes included depression response (≥50% reduction in symptoms) and remission rates at week 10 (as measured by HAM-D, Montgomery-Åsberg Depression Rating Scale [MADRS], and MADRS self-report [MADRS-s] scores), quality of life (measured by EQ-5D-3L), anxiety symptom improvement (Hamilton Anxiety Rating Scale [HAM-A]), and safety. Analysis was conducted with a modified intention-to-treat protocol, excluding 1 participant who withdrew before starting any treatment. The entire trial—including enrollment, consent, device setup, treatment delivery, and outcome assessments—was conducted remotely using videoconference supervision.
Of the 173 participants in the study, 69% were women and 84% were White. They had a mean baseline HAM-D score of 19.07 ± 2.73. The proportion of patients in each group concurrently taking antidepressant medications and/or undergoing psychotherapy was similar.
The investigators noted a statistically significant difference (P=.012; d=.37) between the groups’ primary outcome (depressive symptom improvement): HAM-D scores in the active tDCS group improved by a mean of 9.41 ± 6.25 points (10-week mean HAM-D = 9.58 ± 6.02) compared with a sham arm improvement of 7.14 ± 6.10 points (10-week mean HAM-D = 11.66 ± 5.96). Secondary outcomes also consistently favored active treatment: 10-week MADRS scores improved by 11.31 vs 7.74 points (P=.006), and MADRS-s scores improved by 9.90 vs 6.23 points (P=.009).
Clinical response rates were significantly higher with active tDCS across all measures: HAM-D 58.3% vs 37.8% (P=.017), MADRS 64.2% vs 32.3% (P<.001), and MADRS-s 51.8% vs 25.1% (P=.002). Active tDCS remission rates were similarly superior: HAM-D 44.9% vs 21.8% (P=.004), MADRS 57.5% vs 29.4% (P=.002), and MADRS-s 53.8% vs 23.4% (P=.002). Number needed to treat (NNT) based on response and remission rates ranged from 3 to 5. No significant difference in quality of life was observed between groups (P=.326).
Anxiety symptom improvement was not significantly different between the 2 groups (week 10 HAM-A 6.62-point reduction for active tDCS vs 4.88-point reduction for sham, P=.08). No participants developed mania or hypomania, and week 10 Young Mania Rating Scale scores were low in both groups. Neuropsychological assessments testing verbal learning/memory and psychomotor speed/visuospatial attention revealed no significant differences between treatment arms.
Adverse effects significantly associated with tDCS treatment were skin redness (63.5% active vs 18.5% sham; P<.001), skin irritation (6.9% vs 0%; P=.03), and trouble concentrating (14.1% vs 3.7%; P=.03). Two participants in the active group reported developing “burns” at the left anode site, which the authors believe may have been due to using sponges that had dried out.
At week 10, there was a significant difference between 77.6% of participants in the active treatment arm and 59.3% in the sham treatment arm who guessed they had received active tDCS (P=.01).
This double-blind, randomized controlled trial of adults with moderate to severe MDD demonstrated that a 10-week course of home-based, remotely supervised tDCS is associated with improvements in depressive symptoms and higher response and remission rates compared with sham treatment. Overall, the intervention appears safe and well tolerated.
Home-based tDCS could become a viable and more accessible neuromodulation option for patients with MDD. There were 2 incidents of probable electrode burns associated with home-based tDCS in this trial of supervised in-home treatment; this raises concerns about feasibility and safety, particularly in unsupervised settings. Given the modest effect size, further research is needed to compare tDCS against existing treatments and to more specifically evaluate its efficacy in antidepressant augmentation.
Home-based, remotely supervised tDCS is a safe and modestly effective MDD treatment with the potential to improve access to neuromodulation therapies.
Dr Perez Meek is a fourth-year psychiatry resident at Creighton University in Omaha, Nebraska. Dr Al-Khalila is a second-year psychiatry resident at Creighton University. Dr Bing-Bauer is a first-year psychiatry resident at Creighton University. Dr Dickan is a fourth-year psychiatry resident at Creighton University. Dr Schuster is an assistant professor of psychiatry at Creighton University School of Medicine. Dr Mullen is an assistant professor of psychiatry at Saint Louis University School of Medicine in Missouri. Dr Tampi is a professor and the chair of the Department of Psychiatry at Creighton University School of Medicine and Catholic Health Initiatives Health Behavioral Health Services. He is also an adjunct professor of psychiatry at Yale School of Medicine in New Haven, Connecticut, and a member of the Psychiatric Times editorial board.
Reference
1. Woodham RD, Selvaraj S, Lajmi N, et al.
