“Flow helps the vast majority of people to improve their depression,” reads the latest marketing email from Flow Neuroscience, a Swedish-based company that has been making headlines over the past year with what it describes as an “innovative brain-stimulation treatment” that patients can use in their own homes.
Flow’s users receive a headset that delivers small electrical pulses to an area in the front of the brain called the dorsolateral prefrontal cortex, which is linked to decision making, motivation, planning and working memory, functions that become impaired in depression.
According to Alex O’Neill-Kerr, a visiting professor at the University of Northampton and psychiatrist who specialises in neuromodulation therapies for depression, the concept arises from research which has indicated that the symptoms of depression are linked to impaired connectivity between neurons on one side of the brain. He points to studies using a form of brain imaging called positron emission tomography (PET) scans, which have shown a distinct imbalance in the patterns of how glucose is being used by the brains of depressed individuals compared with non-depressed people.
“You can look at a non-depressed brain, and the glucose utilisation is equal on both sides, front to back, all the same,” he says. “If you look at a depressed brain, the left side seems to be doing nothing. There doesn’t seem to be any activity, and on the right side, there’s often hyperactivity. So this idea started to emerge that depression was something to do with disconnected neurons on the left-hand side of the brain, and maybe we could find something to fix that.”
Over time, this led to a field of therapy known as repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to simultaneously stimulate the left-hand side of the brain while inhibiting the right. In the US, rTMS devices and protocols have gained regulatory approval for depression and have shown consistent efficacy in clinical trials across a range of patients, from mild to severe disease. While rTMS is now widely used in a number of countries, its use has remained limited in the UK due to the costs involved in purchasing the required machinery and establishing dedicated treatment centres. “The NHS has unfortunately been far behind the US and Canada on rTMS, which is at least as effective as antidepressants, if not more,” says Camilla Nord, who leads the Mental Health Neuroscience Lab at the University of Cambridge. “But it has to be done in-clinic by a trained technician or nurse.”
Flow’s technology is an example of a related technology called transcranial direct-current stimulation (tDCS), which attempts to achieve a similar effect to rTMS, but through applying low-level electrical currents to the brain instead of magnetic fields. Because this is safer, it can be self-administered by patients in their own homes, making it far more cost-effective, and it has attracted the attention of a growing number of NHS Trusts. It is also available to buy without a prescription for £399 from pharmacies.
Flow Neuroscience told the Observer that more than 400 NHS patients had received Flow to date, with the therapy being offered to patients in Northamptonshire, Leicestershire and west London. Fifteen other NHS trusts are in discussion with the company about setting up their own Flow programmes.
In October 2024, a phase 2 clinical trial of 174 depression patients, which was sponsored by the company, reported clear benefits. In results detailed in the journal Nature Medicine, 45% of patients who received active treatment with Flow’s device experienced remission of their symptoms over the course of 10 weeks, compared with 22% of those who were given an inactive version of the device as a placebo.
This finding has been heavily marketed by the company, which described it as “groundbreaking” on its Instagram page. But Nord and other independent mental health researchers say that there are still some key questions to be answered, both regarding the overall effectiveness of tDCS as a treatment, and how it might best be used within the NHS.
Mixed data
Across social media platforms and internet forums – from Reddit and Mumsnet to a Facebook group created by Flow Neuroscience – there are numerous stories of people describing how the treatment has helped their symptoms.
Frank Padberg, professor of psychiatry and psychotherapy at LMU University Hospital Munich, has been studying tDCS and says that we should not dismiss these anecdotal reports, but says it is difficult to evaluate a technology based on individual stories.
“It is a pervasive phenomenon in medicine that individual people report impressive healing experiences,” says Padberg. “In depression, there is a particularly strong placebo response and about 30-40% of people living with depression respond to a placebo. Such responses are enhanced by expectations, and we know that they’re higher with novel technologies.”
The complicating factor, as explained by both Padberg and Nord, is that while the Flow-sponsored Nature Medicine trial reported positive results, other independent clinical trials of tDCS for depression have found negligible benefit. When Padberg himself led a shorter six-week trial of tDCS treatment in 2023, it found no significant reduction in depressive symptoms between active and inactive tDCS devices. Another six-week trial of tDCS, published by researchers in São Paulo in January last year, reported similar findings.
“I have seen the campaign by Flow Neuroscience and found it a bit overconfident in its interpretation of recent findings,” says Padberg. “The Nature Medicine trial is clearly important, but was sponsored by Flow, whereas these other two trials were not funded by industry. The overall mixed findings may just reflect that tDCS is not a particularly effective intervention.”
Nord points out that the overall pattern of results to have emerged from clinical trials over the past seven years have been curiously mixed. Perhaps because of this, the Dundee Advanced Interventions Service, an NHS Scotland clinic that provides specialist treatment for people suffering depression and OCD, published a somewhat withering assessment in October 2023. “On the basis of published evidence, there is a lack of compelling evidence that suggests that tDCS is a useful treatment for patients with anything other than mild depression,” the clinic wrote.
In response, Flow Neuroscience told the Observer that about half of all trials for antidepressants also showed no difference between drug and placebo; and a possible reason why other tDCS trials have failed is because they were conducted over shorter time periods, with the patients receiving fewer dosages. The company commented that it feels there is “good evidence” for tDCS as an effective treatment for moderate-severe depression, and that it “respectfully disagrees” with the Dundee service’s conclusion.
The way forward
For Valerie Voon, professor of neuropsychiatry and neuromodulation at the University of Cambridge, one issue that makes it difficult to interpret the recent Nature Medicine trial is that more than three-quarters of the participants who received the active tDCS treatment were able to correctly guess that they had received a working device rather than a placebo. “We know that the expectation effect and placebo effect might play a role,” she says. “So that’s another potential limitation.”
But despite the mixed findings in various trials over the past decade, Voon and Nord feel that it is worth continuing to explore the evidence base for tDCS, particularly as a complementary treatment to either psychotherapy or antidepressant treatment. Nord believes that, for the time being, it should continue to be rolled out more on an experimental or trial basis, while researchers figure out which depression patients can benefit most from the therapy.
“My own view is that tDCS is a relatively mild intervention that could have particular benefit as an add-on intervention to other therapies, ideally once we have figured out things such as the optimal number of sessions and amount of stimulation, as well as the best patients for the treatment,” says Nord.
In particular, Voon feels that there is more evidence that tDCS can help people with depression of moderate severity, compared with patients who have severe treatment-resistant depression and impairment to their quality of life as a result of their illness, and who have already failed to respond to various other treatments.
“The kind of people who are likely to benefit could still be working but they’re struggling a bit,” she says. “They might have needed to take a brief leave of absence, or they’re having difficulties with social interactions.”
Although Flow has been promoted as being highly user-friendly, with patients able to self-administer treatment at home rather than paying several visits to the clinic each week, Voon suspects that some degree of external supervision from NHS staff will always be required.
In the Nature Medicine trial, participants were supported remotely over the course of the 10 weeks with ongoing video consultations, and Voon says that this additional cost to the healthcare service, alongside the cost of supplying the device, needs to be taken into consideration when assessments are made regarding the cost-effectiveness of Flow.
“I’m not convinced that someone who’s moderately depressed would be able to stay compliant with a regimen of using the device for 30 minutes, several times a week over the course of 10 weeks,” she says. “That’s 10 weeks of being quite motivated and rigorous. So I think the consultations will be necessary, which means the NHS will still need to pay someone for their time.”
There is also the possibility that tDCS could be enhanced and made even more effective in future. Although Padberg’s trial reported negative results, he is still excited by the future of the technology and says he doesn’t believe it has been explored to its full potential.
He predicts that a personalised approach will probably be required to give people optimal treatment, using MRI scans to adjust the intensity of the electrical stimulation for each patient. Although this is considerably more expensive, Padberg suggests that it may make it possible to use tDCS to serve more severely treatment-resistant patients successfully in future.
“The variable findings we’ve seen in trials so far just point to the need for developing more individualised treatment protocols,” he says. “You may need to target distinct circuits and networks in the brain that are highly variable from one individual to another, making one-size-fits-all approaches limited.”
