Major depression disorder (MDD) is a disorder with a high prevalence. It is one of the leading causes of work disability worldwide (1). For the treatment of MDD, psychotherapy and/or pharmacotherapy are recommended, depending on the severity of the disease. While pharmacotherapy is available almost everywhere, but is not suitable for all patients and is sometimes associated with considerable side effects or even intolerance, psychotherapy is not always readily available, e.g. in more rural parts of Germany. Furthermore, approximately 33% of patients suffering from MDD have a treatment-resistant course even after guideline-appropriate stepwise therapy with psychotropic drugs and do not respond adequately to pharmacological interventions (2).
Possible alternative non-drug therapies for MDD include non-invasive transcranial brain stimulation (NIBS) techniques. NIBS techniques are well established in experimental neurosciences and have been increasingly used in recent years in the treatment of psychiatric diseases, especially depressive disorders (3, 4).
Studies of the antidepressant efficacy of transcranial direct current stimulation (tDCS) show promising, but not fully consistent, results. Two large, randomized, double-blind, placebo-controlled trials (5, 6) demonstrated significant antidepressant effects of several weeks of treatment with tDCS compared with sham stimulation for MDD. Meta-analyses on the topic also confirm the efficacy of tDCS over placebo in the treatment of MDD (7, 8).
The major advantage of tDCS over the other main NIBS technique, transcranial magnetic stimulation (TMS), is its applicability in a wide range of settings from its use in the MRI scanner to its therapeutic application as a treatment at home, the latter being poorly investigated in studies to date (9). TDCS also has a very favourable side effect profile with the incidence of complications from its use being low (10). The possibility of tDCS home-based treatment has been discussed for some years already, and solutions for technical requirements of its implementation have been developed and presented (11, 12). Given the limitation of psychotherapy availability, as well as the current pandemic situation of COVID-19 in which frequent clinic contacts should be avoided, the concept of a treatment at home with tDCS for MDD is a reasonable option.
So far, the few studies and case reports that have been published investigating a tDCS treatment at home have mainly referred to applications in the neurological field. In this context, application modalities are multifold: Home-based application of tDCS is used in the treatment of cognitive impairment and fatigue in Parkinson's disease, cerebellar ataxia, chronic pain, fibromyalgia, tinnitus and in patients in an apallic state (12–18). In sum, results of the described case reports show good feasibility. Severe side effects were not reported, and a satisfactory degree of safety was stated in larger case series. Reviews on the topic confirm the findings and highlight new opportunities for monitoring (9, 19). No serious side effects of this therapy were found in the 19 studies reviewed by Sandran et al.
In the psychiatric field despite previous absolute treatment resistance, successful partial remission of multimodal hallucinations in two patients with paranoid schizophrenia has been reported using a home treatment approach with tDCS (20, 21). Thus, while the home-based treatment with tDCS has been widely applied and studied in neurological and in specific psychiatric disorders, there are few published studies examining the home use of tDCS in the treatment of depression: In a placebo-controlled study, the home-based application of 20 sessions of 20 minute 2 mA prefrontal tDCS in 26 patients with temporal lobe epilepsy and depressive symptoms was investigated. Results showed good feasibility, but no difference between the groups with regard to the reduction of depressive symptoms equally significant in both groups (22). In another tDCS home-application case series, 12 patients with treatment-resistant and chronic depression were treated with tDCS, partly as maintenance therapy after electroconvulsive therapy (ECT) or rTMS. Significant improvements in depressive symptoms were observed after at least 6 weeks of treatment. The effects lasted in part for several months (23). In an open label, home-based tDCS trial by Alonzo and colleagues (24), 34 patients with unipolar and bipolar depression conducted at least 24 tDCS sessions with the same protocol as HomeDC. Overall, this pilot trial addressed the issue of electrode positioning, supervision, training and control of adherence revealing good antidepressant effects: There was improvement in depressive symptomatology (response rate of 38%), the drop-out rate was very low at 6% of sessions, and outcomes in terms of side effects were similar to those of studies using tDCS in the clinic setting (24). However, a control condition was lacking in this pilot study. Another case series combined home-based tDCS (bifrontal montage, 21 sessions over 6 weeks) with an app-based psychological intervention in five patients with MDD (25). Safety and feasibility were good with a response rate of 80% even in combination with the app-based intervention. Technical parameters were not monitored. In the largest home-based tDCS trial for MDD to date, a placebo-controlled, single-blinded design was used to stimulate the prefrontal cortex in 58 patiens with MDD (2mA, 30 min, 6 weeks (26). Results showed feasibility and a reduction in the Beck Depression Inventory (BDI), significantly higher in the active tDCS group. Some methodological limitations, e.g. the single-blinded design and simultaneous administration of escitalopram of varying dosages, have to be considered. In a small pilot study with in the end only three patients undergoing the study protocol to investigate the safety and feasibility of a home-based, “study companion-administered” tDCS intervention (27). Another very recent study confirmed the feasibility and safety of home treatment with tDCS in an open label design without placebo control using the same parameters as the HomeDC trial for 6 weeks in 26 patients with MDD. Antidepressant effects were promising and long lasting with 91.3% clinical response and 73.9% remission rates even in the 6-month follow up (28). In addition to the results of these pilot studies, case reports, and smaller monocentric single blinded trials, study protocols of larger RCTs on this topic even with the combination of tDCS with cognitive training or behavioural therapy have been published, though the results of these trials are expected in the future (29, 30).
Guidelines for the home-based use of tDCS have emphasized the issues already encountered during the development of the homeDC study design (31):
-
Training and supervision. For the training a checklist (24) and video-training are helpful for standardizing the procedure. Tele-health solutions play an important role at this point (32). The often used approach of an assisted home treatment (27) with a third person (caregiver or family member) seems to be effective especially in the treatment of physically impairing e.g. neurological diseases but less reasonable especially in the treatment of MDD with the idea to save resources and to allow the patient as much autonomy as possible at home.
-
Electrode positioning. Different technical solutions were tested and found for this purpose (20, 21, 33–36). The aim is to combine the highest possible degree of accuracy and individuality with ease of use.
-
Monitoring adherence to the tDCS protocol. Here, too, as described, there are various options ranging from personal consultation to technical options for monitoring stimulation duration and stimulation times as well as a pre-programmed blocking time.
-
Safety monitoring and assessment of targeted outcomes. Outcomes in the psychiatric field are most accurately measurable in the context of a personal rating. Monitoring of the technical stimulation parameters could contribute to safety monitoring and stimulation quality; the more personnel-intensive option is the assisted stimulation.
Based on these critical points particular strengths of the HomeDC trial design are: Cloud-based supervision of technical data and timing, standardized electrode positioning with new caps, and post hoc individual MRI based modeling of electric field (E-field) intensity as putative proxy of the individual dosage needed.
With the cloud-based monitoring and supervision of the technical data, the study provides a contribution to technical achievements, which will allow us to draw objective conclusions about the quality of the stimulations performed. Variability in impedance, current and voltage will be correlated with clinical outcome to find further possible factors influencing the effectiveness of tDCS. It will also be possible to compare the technical data of the HomeDC trial with that of the DepressionDC trial (37) and thus compare stimulation quality between home-based, self-administered tDCS and the on-site application by an operator (DepressionDC). The time tag of the stimulations will be used to check the adherence.
For correct and easy electrode montage in the HomeDC trial, caps with integrated electrodes have been developed. Unlike most contemporaries, these take into account not only the head circumference, but also the distance between the external eye angle and the Cz electrode point; important in the tDCS field as the exact positioning of the electrodes is decisive for the correct stimulation of the target (38).
Based on these standards, the HomeDC trial aims to investigate the feasibility, safety and effectiveness of prefrontal tDCS as a treatment at home for MDD in a placebo-controlled, double-blind, randomized design. In addition, the HomeDC trial implements and tests a cloud based approach for supervising timing and technical data, recently developed in the framework of a large RCT on tDCS in MDD, i.e. the DepressionDC trial (37).