Depression is a common condition that has a significant disease burden on those affected. While medication and psychotherapy are very effective for many patients, they do not work for everyone and can cause some undesirable side-effects, such as gastrointestinal symptoms (e.g., nausea), decreased sex drive or weight gain.

Non-invasive brain stimulation techniques, including transcranial direct current stimulation (tDCS), represent an alternative or add-on treatment option for depression that may have fewer side effects. Treatment with tDCS involves the application of a mild electrical current to the scalp to change how excitable certain parts of the brain are.

Meta-analyses – including two of my own (Mutz J. et al, 2018, 2019) – have generally found tDCS to be effective for treating depressive symptoms. While considered an experimental treatment in most countries, its use in clinical practice is more common in Brazil and parts of Europe. However, one barrier to more widespread use of tDCS is the need for patients to attend frequent visits to the clinic to receive treatment, usually five times per week for several weeks. Therefore, there is now considerable interest in exploring the potential for tDCS use at home.

Studies have demonstrated that home-based tDCS is feasible, however, none of the three previous randomised controlled trials (RCTs) found that tDCS was superior to sham treatment (Borrione L. et al, 2024; Kumpf U. et al, 2023; Oh J. et al, 2022). Two of these trials had a small sample size (less than 60 participants), all were limited to a treatment duration of six weeks and none were fully remote (i.e., all included in-person appointments).

In this new trial, Woodham and colleagues aimed to evaluate a 10-week tDCS treatment protocol in 174 patients and found promising results – spoiler: nearly half the patients in the active treatment group achieved remission, compared to just over 20% in the sham control group. However, as two of the largest tDCS trials conducted to date in clinical settings have yielded negative results (Loo C. et al, 2018; Burkhardt G. et al, 2023), one is left wondering: Is tDCS ready for widespread use?

Methods

The trial included 174 participants (69% women) randomly allocated to active tDCS or sham treatment. tDCS was completed by the participants in their home environment. A researcher was present via videoconferencing only for the initial session. The electrodes were placed over the left and right dorsolateral prefrontal cortex (i.e., on the forehead area), a brain region which is linked to neurophysiological differences observed in depression and is involved in regulating mood and cognitive functions. Sham stimulation involved a brief ramp-up and down to mimic the sensations of real treatment (e.g., tingling) so that the participants’ blinding would be maintained. This means gradually increasing the electrical current at the start of the session and then gradually decreasing it again.

Participants completed five 30-minute tDCS treatment sessions per week for the first three weeks and three sessions per week for the remaining seven weeks. Remote supervision was provided via videoconferencing to ensure appropriate device use. Two-thirds of patients were on stable antidepressant medication for at least six weeks prior to participation. Patients and researchers, including the outcome assessors, were blinded to treatment group (i.e., the trial design was double-blind).

Results

Patients in both the active tDCS and sham treatment groups experienced a decrease in depressive symptoms. However, reductions were greater in the active group, with statistically significant differences in the primary outcome, the Hamilton Depression Rating Scale (HDRS), at week 10 (95% confidence interval 0.51 to 4.01, p = 0.012). Differences between groups were also statistically significant at week four, but not at week seven. The reasons for the latter are unclear, but it is worth noting that the difference in symptoms assessed using the Montgomery-Åsberg Depression Rating Scale was also statistically significant at week seven.

Response rates, defined as a symptom decrease of at least 50%, were 58.3% in the active group and 37.8% in the sham group. Clinical remission rates, defined as a HDRS score of 7 or less, were 44.9% in the active group and 21.8% in the sham group. These effects were observed across both clinician-rated scales and a self-report scale. The trial was discontinued early based on the results of a pre-specified blinded interim analysis suggesting the treatment is efficacious.

tDCS treatment had a good safety profile. There was no overall difference in discontinuation rates between groups (14.9% and 13.7% in the active and sham groups, respectively). While transient side effects, such as skin redness, irritation and trouble concentrating, were more common in the active group, no serious adverse events were reported. Two participants in the active group experienced skin burns, which the authors speculate may be due to use of dried sponges. There was no evidence of differences in neuropsychological function, assessed using standardised tests, between the active and sham groups, suggesting that tDCS had neither beneficial nor adverse cognitive effects.

The authors also examined the effect of tDCS treatment on several other outcomes, such as anxiety and manic symptoms. One outcome that I found worth highlighting is quality of life. The authors observed no difference in overall quality of life between the active and sham groups. However, it is not obvious that a difference is to be expected after just 10 weeks of treatment. The measure of quality of life included items on five dimensions (mobility, self-care, usual activities, pain and discomfort), most of which reflect long-term, fairly stable factors. Moreover, the quality-of-life scores of the patients in this trial were high to start with, meaning there was limited room for improvement in these domains.

Challenges with blinding were notable: 77.6% of the participants in the active treatment group correctly guessed their treatment allocation, compared to 59.3% in the sham group. This could have influenced outcomes and may, in part, be due to visible side effects, such as skin redness, occurring more frequently in the active treatment group.

Conclusions

This RCT provides evidence supporting the feasibility and efficacy of fully remote home-based tDCS for treating depressive episodes of at least moderate severity. The treatment had a good safety profile, and no serious adverse events were reported.

The authors concluded that home-based tDCS offers a promising, non-invasive option that may serve as a first-line treatment for some patients (for example, those who do not prefer drug treatment), particularly given its portability and ease of administration. Identifying patient and/or treatment-related characteristics that predict a favourable treatment response in future research could further improve patient outcomes.

Strengths and limitations

The sample size of the trial was comparable to the largest tDCS trials completed to date in clinical settings. The use of both clinician-rated and patient-reported outcomes provides a good overview of treatment efficacy, and the 10-week duration distinguishes this trial from prior home-based tDCS trials, which were only up to six weeks long. The authors also report how many patients in their study received psychotherapy while participating in this trial (10.3% of the sample), which is an important variable rarely reported in brain stimulation trials.

Blinding challenges are a limitation in this study. The high rate of correct guesses in the active group (77.6%) compared to the sham group (59.3%) suggests that side effects, for example skin redness, may have influenced participant perceptions. The occurrence of electrical burns in two patients highlights the practical challenges in ensuring safe device use at home. This trial was remotely supervised and not full do-it-yourself tDCS. Interestingly, the sham response was about 10% lower in the present trial than in two previous home-based tDCS trials, likely because of it being fully remote and thus did not involve the experience of attending a clinical setting.

The sample’s relatively young (mean age ~37-38 years) and highly educated (1/4 of participants had a Masters or Doctoral degree) demographic could limit the generalisability of these findings to other populations. The sample composition likely reflects the trial’s recruitment strategy, which was done, in part, through the website of the device manufacturer. The moderate depression severity of the sample limits generalisability to more severe episodes of depression. The range of the HDRS is 0 to 52, and the sample average was 19.07 (SD = 2.73). Mild depression is usually defined by scores between 8 and 16, moderate depression by scores of 17 to 23 and severe depression by scores of at least 24. Patients with ‘treatment-resistant’ depression, according to the most common definition of at least two failed prior treatment attempts, were excluded from this trial.

Finally, it is worth keeping in mind that some investigators had financial ties to the device manufacturer and sponsor of the trial, Flow Neuroscience.

Implications for practice

tDCS is an alternative or add-on treatment option for patients with depression of at least moderate severity. A barrier to more widespread use of tDCS, and other non-invasive brain stimulation techniques, is the need to attend frequent visits to the clinic. tDCS delivered in the home setting, which resulted in higher response and remission rates than sham treatment in this trial, could increase accessibility to this treatment.

These positive results are encouraging but must be considered in the context of other tDCS trials. Two of the largest tDCS trials conducted in clinical settings yielded negative results (Loo et al., 2018; Burkhardt et al., 2023) and none of the previous home-based tDCS trials found the treatment to be superior to sham (Borrione L. et al, 2024; Kumpf U. et al, 2023; Oh J. et al, 2022).

The safety profile of home-based tDCS is good, with no serious adverse events reported. However, the occurrence of skin burns in two patients in the active treatment group highlights the need for careful safety monitoring and guidance. Policymakers should consider developing safety monitoring frameworks to support home-based tDCS treatment and to minimise risks.

Is home-based tDCS ready for widespread use? I am cautiously optimistic given that this trial supports treatment efficacy and suggests a good safety profile. No existing treatment option, whether drugs, psychotherapy or other brain stimulation technique, works in all patients. tDCS should thus be considered as an alternative or add-on treatment, depending on patient preference and clinician guidance, in those with depressive symptoms of at least moderate severity.

Future studies should focus on further improving patient outcomes by identifying predictors of response, and clarify which patients are most likely to respond to which type of treatment.

Statement of interests

I have previously co-authored publications with three of the authors of the current paper (Woodham, Young and Fu) but have not been involved in this trial.

Links

Primary paper

Woodham, R. D., Selvaraj, S., Lajmi, N., Hobday, H., Sheehan, G., Ghazi-Noori, A. R., … & Fu, C. H. (2024). Home-based transcranial direct current stimulation treatment for major depressive disorder: a fully remote phase 2 randomized sham-controlled trial. Nature Medicine, 31, 87-95. https://doi.org/10.1038/s41591-024-03305-y

Other references

Borrione, L., Cavendish, B. A., Aparicio, L. V., Luethi, M. S., Goerigk, S., Ramos, M. R., … & Brunoni, A. R. (2024). Home-use transcranial direct current stimulation for the treatment of a major depressive episode: a randomized clinical trial. JAMA Psychiatry, 81(4), 329-337. https://doi.org/10.1001/jamapsychiatry.2023.4948

Burkhardt, G., Kumpf, U., Crispin, A., Goerigk, S., Andre, E., Plewnia, C., … & Padberg, F. (2023). Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial. The Lancet, 402(10401), 545-554. https://doi.org/10.1016/S0140-6736(23)00640-2

Kumpf, U., Palm, U., Eder, J., Ezim, H., Stadler, M., Burkhardt, G., … & Padberg, F. (2023). TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. European Archives of Psychiatry and Clinical Neuroscience, 273(7), 1403-1420. https://doi.org/10.1007/s00406-023-01620-y

Loo, C. K., Husain, M. M., McDonald, W. M., Aaronson, S., O’Reardon, J. P., Alonzo, A., … & Galvez, V. (2018). International randomized-controlled trial of transcranial direct current stimulation in depression. Brain stimulation, 11(1), 125-133. https://doi.org/10.1016/j.brs.2017.10.011

Mutz, J., Edgcumbe, D. R., Brunoni, A. R., & Fu, C. H. (2018). Efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression: a systematic review and meta-analysis of randomised sham-controlled trials. Neuroscience & Biobehavioral Reviews, 92, 291-303. https://doi.org/10.1136/bmj.l1079

Mutz, J., Vipulananthan, V., Carter, B., Hurlemann, R., Fu, C. H., & Young, A. H. (2019). Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: systematic review and network meta-analysis. The BMJ, 364. https://doi.org/10.1016/j.neubiorev.2018.05.015

Oh, J., Jang, K. I., Jeon, S., & Chae, J. H. (2022). Effect of self-administered transcranial direct stimulation in patients with major depressive disorder: a randomized, single-blinded clinical trial. Clinical Psychopharmacology and Neuroscience, 20(1), 87-96. https://doi.org/10.9758/cpn.2022.20.1.87

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