NICE has developed a medtech innovation briefing (MIB) on Flow transcranial direct current stimulation for treating depression.

The information provided includes a description of the technology, how it’s used, and its potential role in the treatment pathway. A MIB also includes a review of relevant published evidence and the likely costs of using the technologies, but they are not NICE guidance and do not make any recommendations on the value of using the technologies.

What are NIBs?

Medtech Innovation Briefings

Please note, from April 2023 NICE will no longer produce Medtech Innovation Briefings (MIBs) on behalf of NHS England.

MIBs were commissioned by NHS England and produced in support of the NHS5-year Forward View (2014), as one of a number of steps to accelerate innovation in new treatments and diagnostics.

MIBs are NICE advice designed to support NHS and social care commissioners and staff when considering using new medical devices and other medical or diagnostic technologies.

The information provided in a briefing includes:

• a description of the technology
• how the technology is used
• the potential role in the treatment pathway
• a review of relevant published evidence
• the likely costs of using the technology.

Summary

• The technology described in this briefing is the Flow transcranial direct current stimulation (tDCS) headset and behavioural therapy app. It is used for treating depression.
• The innovative aspects are that it targets the physical causes of depression and delivers medication-free treatment at home. A clinician monitors treatment and response through a remote monitoring portal.
• The intended place in therapy would be as a first treatment for moderate to severe depression, or if the condition has not responded to other treatments.
• The main points from the evidence summarised in this briefing are from 4 studies (1 multicentre, double-blind, superiority randomised controlled trial, 1 open-label, single-arm feasibility study, 1 acceptability study, and 1 retrospective case series) including a total of 206 people. The studies show that Flow does improve symptoms of depression. There are also many published studies on tDCS systems other than Flow.
• A key uncertainty around the evidence is that it is yet to be published in peer-reviewed papers.
• Experts advised that Flow is an innovative technology, which would particularly benefit people whose symptoms have not improved with existing interventions or who have side effects with commonly prescribed medicines, such as antidepressants. They said that it can also be used as a first treatment. The clinical experts also said that Flow could be used at home rather than people needing to attend primary and secondary care appointments, which would further reduce the cost of treating depression.
• The cost of the Flow headset is £399, which includes a 6‑week supply of electrode pads. There is also an option for rental, which is £79 per month including the headset and a month’s supply of electrode pads. The Flow app is free.

NICE is committed to promoting equality of opportunity, eliminating unlawful discrimination, and fostering good relations between people with particular protected characteristics and others.

Depression can have a significant effect on people’s daily lives. Someone is disabled if their depression has a substantial and long-term adverse effect on their ability to do daily activities. Some groups of people may be less likely to access psychological interventions, such as ethnic minority groups, older people, people in prison, or people who are in contact with the criminal justice system, and ex-service personnel. Women are more likely than men to have depression. Disability, race, age, and sex are protected characteristics under the Equality Act 2010.

A literature search was carried out for this briefing in accordance with the interim process and methods statement for MedTech innovation briefings. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting [email protected].

Published evidence
Four studies are summarised in this briefing, which include a total of 206 people.

The evidence consists of:

• 1 multicentre, double-blind, superiority randomised controlled trial
• 1 open-label, single-arm feasibility study (Woodham et al. 2022), which has 1 accompanying study in which people completed questionnaires and had interviews to determine acceptability (Rimmer et al. 2022)
• 1 retrospective case series (Sobral et al. 2022).

There is also 1 expert opinion paper (Borrione et al. 2020) and 1 case series reported in a research letter (Borrione et al. 2021), which are not summarised here.

The clinical evidence and its strengths and limitations are summarised in the overall assessment of the evidence.

Overall assessment of the evidence
The existing evidence for the technology is of high, moderate and low quality. There is high-quality, comparative evidence from the UK that Flow can improve symptoms of depression and lead to remission. This evidence is from people using the technology at home.

There is also evidence from supervised sessions of transcranial direct current stimulation (tDCS) in the UK. There are further large-scale comparative studies due to finish in 2023.

Empower trial (2023)
Study size, design and location
A multicentre, double-blind, superiority randomised controlled trial in 173 adults with non-treatment-resistant unipolar depression. The study was done in the UK and US.

Intervention and comparator
Flow FL‑100 tDCS compared with sham tDCS.

Key outcomes
In the trial, 86 people had active tDCS and the other 87 people had sham tDCS. In a modified intention-to-treat analysis, the mean (plus or minus standard deviation) change in the score from baseline to week 10 was -10.2 plus or minus 5.4 points in the active tDCS group, and -7.8 plus or minus 5 points in the sham group. Active tDCS was superior to sham; the adjusted difference compared with sham was -2.2 points (95% confidence interval [CI] -3.9 to -0.5; p=0.013). The Hamilton Depression Rating Scale‑17 (HDRS‑17) response rate (defined as at least a 50% reduction from baseline) was 53.6% and 28.6% (odds ratio [OR] 2.88; 95% CI 1.42 to 5.84; p=0.003), respectively. The HDRS‑17 remission rate (a score of 7 or less) was 45.2% versus 22.7% (OR 2.80; 95% CI 1.37 to 5.72; p=0.005). The Montgomery–Åsberg Depression Rating Scale (MADRS) response and remission rates (a score of 10 or less) for the active group versus the sham group were 62.6% versus 32.7% (OR 3.45; 95% CI 1.66 to 7.18; p<0.001) and 57.1% versus 30.2% (OR 3.08; 95% CI 1.44 to 6.57; p<0.003), respectively. The active tDCS group had significantly higher instances of dry skin and skin irritation, and no serious adverse events related to the device were reported.

Strengths and limitations
The study shows that tDCS leads to improvements in clinical symptoms of depression. All the people in the study had the treatment unsupervised at home, as would be expected with actual treatment. Most people were recruited in the UK (115 in the UK and 58 in the US). The study is of high methodological quality because it is a double-blind randomised controlled trial. But according to the Empower entry in the clinical trials database, this study is still active and not recruiting, and the full results from the trial are awaiting publication. The evidence presented here is limited by the results only being published as a non-peer-reviewed abstract on the company’s website.

Woodham et al. (2022)
Study size, design and location
An open-label, single-arm feasibility study of 26 people with moderate to severe depression who had tDCS. The study was done in the UK.

Intervention and comparator
Flow or Starstim (Neuroelectrics), no comparator.

Key outcomes
Two tDCS devices were used in the study: Neuroelectrics Starstim 8 system (n=3) and Flow (n=23). tDCS was used in addition to existing treatment (for example, antidepressants or cognitive behavioural therapy). Starstim needs a second person to place the electrodes on the scalp, while Flow uses a fully remote protocol with real-time remote supervision. Results were not reported separately for each device. For all 4 time points (baseline, 6 weeks, 3 months and 6 months), 88.5% of people (n=23) completed clinical assessments. Data was missing for 7.7% of people (n=2) at the end of treatment (week 6) and 11.5% (n=3) at the 3- and 6‑month follow up.

At week 6, mean HDRS‑17 score was 5.33; 22 people (91.7%) showed a significant clinical response and 21 people (87.5%) had clinical remission. At the 3‑month follow up, mean HDRS‑17 score was 5.65; 20 out of 23 people (87.0%) had a clinical response, and 18 out of 23 people (78.2%) had clinical remission. At the 6‑month follow up, mean HDRS‑17 score was 5.43; 21 out of 23 people (91.3%) had a clinical response, and 17 out of 23 people (73.9%) had remission. Four people (16.7%) showed an early clinical response after 2 weeks of treatment (10 tDCS sessions), and 3 people had remission (12.5%). Significant clinical improvements from baseline were maintained at the 6‑month follow-up in the intention-to-treat analysis.

Strengths and limitations
The study suggests that using tDCS can lead to improvements in clinical symptoms of depression. All of the people in the study were based in the UK. The lack of a control treatment arm is a limitation of the study. The authors said that the trial protocol was not designed to establish efficacy, which would have needed a control treatment group. Real-time supervision for each session is likely to have contributed to symptom improvement, and this would not be available for people using the technology outside of research.

Rimmer et al. (2022)
Study size, design and location
A study examining the acceptability of tDCS treatment for depression using questionnaires and individual interviews from 26 people who had a 6-week trial of community-based tDCS. This study was done in the UK.

Intervention and comparator
Flow, no comparator.

Key outcomes
Responses to the survey were gathered at 3 time points: before the start of treatment, at the end of treatment (6 weeks), and at the 6‑month follow up. The questionnaire included 5 questions on:

• general acceptability
• perceived effectiveness
• side effects
• ethics (how ethical tDCS is)
• burden (how much effort is needed for each tDCS session).

Responses were rated on a 7‑point anchored Likert scale ranging from, for example, ‘very acceptable’ to ‘very unacceptable’, with the opportunity for open-ended responses.

Median acceptability was ‘very acceptable’ at each time point, with no significant changes over time. Median response to the question on ethics was ‘very ethical’ for all time points, with no significant changes over time. Burden remained consistent at ‘little bit more than usual’, with no significant changes. Ratings for perceived effectiveness increased from ‘quite helpful’ at baseline to ‘very helpful’ at follow up, but this increase was not significant. Similarly, there was an insignificant decrease in response to the side effects question, from being ‘a bit unlikely’ at baseline to being ‘very much unaffected’ or ‘quite unaffected’ at follow up. There was a significant increase in endorsements of the technology, from ‘would recommend tDCS’ at the end of treatment (20.8% of people) to ‘would strongly recommend’ at follow up (55.6% of people).

Strengths and limitations
This study used people from the Woodham et al. (2022) study, so there was no control treatment arm. Each session had real-time supervision, and this additional support, compared with actual clinical practice, may have contributed to the high response rates and increased perceived effectiveness of the treatment.

Sobral et al. (2022)
Study size, design and location
A retrospective case series from 7 people who presented with mild to moderate depression that was resistant to medication or who showed a preference for non-pharmacological treatments. The study was done in Portugal.

Intervention and comparator
Flow, no comparator.

Key outcomes
The case series reported the effect of 6 to 10 weeks of self-administered tDCS with Flow. Symptoms of depression were assessed using MADRS and the Beck Depression Inventory (BDI‑II). Anxiety symptoms were measured using State–Trait Anxiety Inventory (STAI). The significance of clinical improvement was assessed using the Reliable Change Index (RCI). A significant improvement in depressive symptoms was found in 5 out of 7 people (RCI -1.45), with a range of percentage change in MADRS of 37.9% to 66.7%. A significant improvement in BDI‑II score was seen in 4 people (-3.61), ranging from a 57.1% change to 100%. For anxiety symptoms, significant improvement was seen in 5 people (RCI -1.79), with a percentage change in STAI score ranging from 12.3% to 46.4%. The most common side effects were found to be a mild tingling sensation and scalp discomfort, but tDCS was generally accepted and well tolerated.

Strengths and limitations
This was a case series of a relatively small number of people with depression and anxiety. tDCS was self-administered, as would be expected with actual treatment. All of the people except 1 were having cognitive behavioural therapy or taking medicines during the study period, so findings may be confounded. There was a lack of follow-up for most people in this study and notable heterogeneity both in baseline symptoms and in treatment protocols.

Sustainability
No sustainability claims have been made by the company.

Recent and ongoing studies
Psychological interventions and tDCS for treating major depressive disorder. NCT04889976. Status: completed. Indication: major depressive disorder. Device: Flow. Study completion date: October 2022. Country: Brazil.

Comments on this technology were invited from clinical experts working in the field and relevant patient organisations. The comments received are individual opinions and do not represent NICE’s view.

All 3 experts were familiar with or had used this technology before.

Level of innovation

All of the clinical experts agreed that Flow is a novel technology compared with standard care in clinical practice. One expert highlighted that Flow combines transcranial direct current stimulation (tDCS) with behavioural therapy. Another expert explained that this technology uses a novel approach for treating depression and anxiety because it focuses on neuromodulation and neuroplasticity rather than chemical imbalances. This is supported by functional MRI imaging, which has shown changes in the connectivity of different parts of the brain in people with depression and anxiety. One expert thought that Flow would be used in addition to standard care, which is antidepressants and psychological treatment. The other 2 experts believed that Flow had the potential to be a new treatment option, particularly for people who have depression that has not responded to current treatments. One expert put forward evidence that tDCS is less effective in treatment-resistant depression.

Potential patient impact

One expert said that Flow can be used as a home-based treatment rather than people needing to attend primary and secondary care. Two of the experts said that tDCS is generally well tolerated, as shown by the evidence, with minimal to no side effects. They also said that the technology can be offered as a first treatment for people with depression, which would reduce the need to prescribe antidepressants. One expert said that Flow offers an objective method of monitoring mental health state and providing feedback to people with the condition. All the clinical experts agreed that Flow would particularly benefit people whose symptoms have not responded to existing interventions or who experience side effects with commonly prescribed medication, such as antidepressants.

Potential system impact

The clinical experts outlined the cost to the NHS of anxiety and depression each year, with a large proportion being made up of secondary care costs. Two of the experts said that some people may not need secondary care if tDCS is prescribed in primary care. This would mean that Flow is used as a first treatment for people with depression. The one-off cost for purchasing the Flow headset is likely to be cheaper than antidepressants, which are not effective for some people. Because Flow is intended to be used at home, it is likely to reduce the number of secondary care appointments needed, which could further reduce the costs of treating depression.

General comments

None of the clinical experts were aware of any issues that could prevent this technology or procedure being adopted in the NHS. They also advised that no change in facilities is needed for adopting Flow, but a short training session is needed for clinicians. They agreed that the system is very simple to set up and use. The experts outlined the potential adverse events related to the technology. The most common is skin redness or skin burns. One of the experts suggested that it would be useful to see further randomised controlled trials comparing Flow with standard care treatments to determine its efficacy.

The following clinicians contributed to this briefing:

• Danny Allen, consultant psychiatrist, Phoenix Mental Health Services. Did not declare any interests.
• Alex O’Neill-Kerr, consultant psychiatrist and medical director, Northamptonshire Healthcare NHS Foundation Trust. Has 3 Flow devices on loan for use by people in private practice and 1 device in NHS practice.
• Cynthia Fu, professor of affective neuroscience, University of East London and King’s College London. Principal investigator for Empower clinical trial (NCT05202119). Provides transcranial direct current stimulation devices for study NCT05436613.

This briefing was developed by NICE.

The interim process and methods statement for MedTech innovation briefings sets out the process NICE uses to select topics, and how the briefings are developed, quality-assured, and approved for publication.

ISBN: 978-1-4731-5513-8