Globally depression causes 7.5% of all years lived with disability, the largest contributor to disability and is defined as experiencing a low mood and loss of pleasure or interest in activities, and can include symptoms such as poor concentration, feelings of low self-worth, hopelessness, suicidality, disrupted sleep, and fatigue [1] . In Great Britain (GB) around one in six (16%) of the general population experience depression [2] . Depression symptoms can have a severe negative impact on everyday functioning and quality of life [1] [3] and depression is the most common mental illness factor determinant of death by suicide [4] . The mortality risk for suicide among patients with major depression has been calculated to be 20 times that where major depression is not present [5] . Severe mental illnesses (SMI) are psychological problems causing severe functional and occupational impairment, and the prevalence of depression in people experiencing SMI is higher than in the general population [6] .

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation by weak electrical currents (0.5 - 2.5 mA) and has been used in addressing various mental illnesses [7] . Electrode placement for treating depression typically involves the anode over the left dorsolateral prefrontal cortex (DLPFC) (F3) and cathode over the right DLPFC (F4) [8] . tDCS mechanisms of action include significant gray matter increases in brain regions functionally connected with the stimulation target, including the bilateral DLPFC, bilateral posterior cingulate cortex, subgenual anterior cingulate cortex, the right hippocampus, thalamus and left caudate brain regions; tDCS leads to neurostructural changes at predetermined brain targets in depression, and plasticity effects may propagate over brain networks [9] .

Meta-analyses of the results of randomised sham-controlled trials show tDCS can significantly improve depressive symptoms and clinical response, with remission being significantly better than placebo sham stimulation [10] - [13] . tDCS is effective as a standalone treatment or in combination with other anti-depression treatments [13] . tDCS is safe [13] and generally reported by patients as acceptable and well-tolerated, with mild and transient physical sensations that usually do not prevent use: burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%) [7] [14] .

Treatment resistant depression (TRD) can be defined as no response to at least two consecutive courses of antidepressant medication [15] . A systematic review of evidence of tDCS for TRD found favourable evidence that tDCS is clinically effective as measured by response, symptom improvement and remission in comparison to sham treatment [16] .

“Flow” combines tDCS (delivered by Flow FL-100 device) and software application wellbeing behaviour training (physical exercise, nutrition, mindfulness, sleep, and choosing actions). A randomised sham-controlled trial of Flow FL-100 in major depressive disorder (MDD) found significant improvement in depression symptoms following 10 weeks of treatment, with a clinical response of 58.3% and a remission rate of 44.9% [17] . A “real world” health service open-label primary care patient study of Flow found depression reliable improvement and remission rates of 58.1% and 32.3%, and significant improvement in depression, every-day functioning, and quality of life [18] [19] . Qualitative studies undertaken on experience of Flow found most patients reported that Flow improved depression symptoms, was acceptable, and that they would recommend it to others [20] - [22] .

This open-label patient cohort study investigates if Flow FL-100 tDCS and behaviour change wellbeing training can be successfully introduced to the treatments offered by a Crisis Resolution & Home Treatment (CRT) service. It assesses the impact of Flow in treating depression for people with SMI. The study addresses the questions: “what are the depression reliable improvement and remission rates?” and “can Flow significantly reduce depressive symptoms and improve real world functioning (every-day, social and occupational functioning) and health-related quality of life?”

Flow delivered tDCS can be provided to patients by a CRT service, and when offered patients will choose to use Flow. Flow reduced impaired functioning, depression symptoms, and thoughts of suicide/self-harm, and increased health related quality of life in CRT patients with symptoms of depression. This supports the evidence of effectiveness of tDCS in reducing depression symptoms [10] - [13] [17] .

The statistically significant improvements in the “ability to perform usual activity” and “self-care” dimensions were measured by the EQ-5D-5L, and impaired functioning was measured by the WSAS. This indicates the positive impact of Flow on self-management, mental health recovery, and real-world functioning, which are factors highly valued by people in their everyday lives. They can also increase resilience, sense of meaningfulness, and purpose in life [35] .

A high average PHQ-9 baseline score (depression in the highest “severe” range) was seen in this study’s participants, indicating the potential value of Flow for those with severe depression. Many of the participants in this study would meet the definition of TRD, this study’s results add evidence to the potential value of tDCS in treating TRD [16] . In this study, tDCS was delivered to patients, most of whom were on antidepressants, and this combination can possibly enhance overall outcomes [13] .

The participants in this study had high rates of self-harm, which is typical of people with SMI [36] . People who self-harm have high rates of depression [37] [38] . Depression is a predicting factor in suicide attempts in those with histories of self-harm [39] . Treating depression is particularly important for those self-harming, as self-harm increases the risk of suicide [40] . A systematic review and meta-analysis examining the efficacy of suicide and self-harm psychosocial interventions found interventions were no more effective than in control groups in reducing self-harm, suicidality, depression, hopelessness, or suicide attempts [41] . Meta-analyses of RCTs found that psychotropic medications to treat and prevent self-injurious thoughts and behaviours produce only small treatment effects [42] , and there is no treatment effect on repetition of self-harm for newer generation antidepressants [43] . These findings highlight the need for effective self-harm treatment. tDCS at the right inferior frontal gyrus may have a positive influence on emotional regulation, i.e., lower impulsiveness agitation and, by doing so, has the potential to decrease non-suicidal self-injury frequency [44] . The potential for tDCS to reduce depression and specifically suicidal and self-harm thoughts seen in this study indicates the potential value of using tDCS.

In this study, there was a relatively quick (six-week) improvement in depression symptoms, and another study showed Flow provided good rates of depression remission at three weeks [19] . Serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs) antidepressants time course of response around 2 to 4 weeks to achieve significant benefits; but it may take longer to achieve most of the improvement [45] . Therefore, Flow might be considered as a treatment where a relatively quick relief of depression symptoms is required, of particular value in CRT patients to address or prevent a mental crisis which may lead to suicide attempt, self-harm, or acute mental health ward admission.

A systematic review and meta-analysis showed that tDCS plus SSRI antidepressant medication provided significant improvement in depression and achieved a significantly higher response rate than sham intervention, and that this was more effective than tDCS treatment alone [46] . This finding is important for clinical practice, as it indicates that patients should continue their existing prescribed SSRI antidepressant use during tDCS treatment, and that patients can start using both tDCS and SSRIs at the same time (Wang et al., 2021) [46] . The majority of patients in this current study were prescribed antidepressants.

For those who have failed to respond to antidepressant medication or psychotherapy or who find medication side effects intolerable, or factors related to psychotherapy unacceptable (e.g., waiting times, travel costs, time required, other commitments preventing attendance), Flow tDCS can be an alternative treatment option. The NHS “Mental Health and Wellbeing Plan” states: “We know there are limitations to the current treatment offer. More needs to be done… to diversify the range of treatments available” [47] . CRT service is well-placed to deliver Flow tDCS treatment as they provide patients with a named keyworker, access to a psychiatrist, and seeks to understand a patient’s individual circumstances and provide individualised support and treatment.

Not all participants experience remission or reliable change following the use of Flow. In a CRT patients are told they may need to try a number of antidepressant treatment options and a combination of treatments. A CRT service’s active engagement with its patients enables it to prepare them for non-treatment response and ensure that they receive ongoing support, and access to other antidepressant treatments.

There were several limitations of the study. There was no control group, a relatively small sample size, and the treatment with Flow tDCS was open-label and adjunct to any existing depression or other treatments or therapies. The sample was over-represented by females, and so the results are less generalisable to males. This study collected outcome measures after six weeks of treatment, with no later follow-up data collection; it is recommended that future studies employ additional follow-up data collection points: 12, 24 and 36 weeks. The participants were from a single UK county reducing generalisability; however, this county has the most ethnically diverse population in the UK outside of London.

Flow tDCS can be fully and effectively integrated into CRT depression treatment. CRTs are willing to offer, and their patients will choose to use Flow, providing evidence of the acceptability of and demand for Flow FL-100 delivered tDCS and software app behaviour change wellbeing training. Flow tDCS can be effective against depression symptoms when offered through a CRT for patients with depression symptoms. Treating depression symptoms, thoughts of self-harm and suicide, improving functioning and quality of life using tDCS in a CRT service may prevent mental health in-patient admission, reduce A&E attendance, and prevent the need for more costly transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT) depression treatment; and, therefore, may reduce healthcare costs. Patient delivered antidepressant treatment at their home reduces burden on patients attending outpatient depression treatment options such as TMS or ECT.

There is a need to offer patients a wide choice of effective depression treatment options. This study’s results support the use of Flow tDCS as a treatment option for people in a CRT service with symptoms of depression. More evidence is required on the long-term effectiveness of tDCS and the potential need for ongoing maintenance sessions to sustain benefits. Future studies could also look into the patient-experience of Flow tDCS for patients in CRT services through qualitative interviews.

We wish to thank the participants and the staff at the NHS Trust for their support in recruitment.

Funding was provided by Flow Neuroscience AB, but study design, analysis, interpretation, and reporting were independent of Flow Neuroscience AB’s involvement.