Novel MRI technique to ease treatment for severe depression

Depression can be a serious concern, with changing lifesyle mental health is detoriating to a greater extent and novel techniques have to be evaluated as a better treatment option.

Using MRI and tracking to guide the delivery of magnetic stimulation to the brains of people with severe depression will see their symptoms ease for at least 6 months. This could vastly improve patients' quality of life. That's according to a major clinical trial funded by an NIHR and Medical Research Council (MRC) partnership.

The results of the BRIGhTMIND trial have been published in Nature Medicine. They found that on average, participants showed substantial improvements in the severity of their depression, anxiety and thinking, with better function and quality of life over 26 weeks with MRI neuronavigated Transcranial Magnetic Stimulation (TMS). This was a substantial increase on the previous reported improvements lasting only 1-3 months.

TMS is an outpatient treatment where people have powerful magnetic pulses delivered to the left side of their head. The person is conscious and has 20 sessions over a 4-6-week period. The method has been used since the 1980s to treat people with severe depression. But, by targeting the precise area of the brain where stimulation is thought to be helpful, there is now evidence for a longer lasting benefit of this treatment.

Major depression is the leading cause of disability lost years worldwide according to the World Health Organisation. Suicide from depression is the biggest killer in people aged between 15-49. Antidepressants and therapy delivered as first or second-line treatments help two thirds of people with depression. However, the remaining third have treatment resistant depression (TRD). This is defined as a lack of response to 2 courses of antidepressants.

The aim of the trial was to look at whether the effects of using TMS could be extended to at least 6 months. This would mean that patients with TRD who respond to the treatment might only require 1 to 2 courses of treatment each year. This may help them to remain relatively well and free from symptoms of depression.

The trial, the first of its size in the world to look at outcomes at 6 months, suggests this might be achievable. It could be possible using functional MRI with TMS to define the exact area of the brain to target. MRI is not normally used to deliver this treatment.

The team used neuronavigation, a computerised tracking system using light, to deliver the TMS. This is a way of precisely pinpointing the area of stimulation. This enables the same area to be targeted at all 20 treatment sessions.

Richard Morriss, Professor of Psychiatry in the School of Medicine and Lead for the Centre for Mood Disorders at the Institute of Mental Health at the University of Nottingham, said: “Ideally when people come for a TMS session, they would sit in the exact same place, but this is rarely going to happen. This method uses light from both ear lobes and the top of the nose to measure the stimulation point from the first time a patient has the treatment. The MRI personalises the site of stimulation and then neuronavigation makes sure the same site is being stimulated at each treatment session. This reduces the variability in stimulation at each session. Since the magnetic pulse can be focused, there are usually only minor short-lasting side-effects, and the person can return to their daily activities immediately on return from the hospital.”

A total of 255 participants took part in the trial, all completing 20 TMS sessions. Patients already in specialist mental health services were recruited. Both Primary Care trusts and GPs were also approached. All participants needed to be referred by their GP to take part.

Over two thirds of participants responded to the treatment, with a third showing 50% improvement in terms of their symptoms and a fifth managing to move into remission and stay there.

“Given these patients are people who have not responded to two previous treatment attempts and have been ill for an average of 7 years, to get such a significant response rate and a fifth who have a sustained response is really encouraging,” said Professor Morriss.

He adds: “Patients who responded to the treatment could stay relatively well compared to how they were previously, with as little as one or two treatments a year. The changes we saw were substantial, not only in reducing their depression symptoms, but they were large enough to improve concentration, memory, anxiety and subsequently their quality of life. The results have already persuaded three NHS Mental Health Trusts, including Nottinghamshire Healthcare NHS Foundation Trust, to routinely offer new TMS services for treatment resistant depression.”

One of the participants of the trial said: “It has been a privilege to work alongside the research and clinical teams and feel that you are making an important contribution to such a groundbreaking study from a patient perspective. The next challenge is to make transcranial magnetic stimulation a standard and universally available treatment option for difficult to treat depression."

Professor Danny McAuley, Scientific Director for NIHR Programmes, said: “Once again, high quality research funded by NIHR and MRC is making a step change in improving health and care services. It’s brilliant to see three UK mental health trusts are now routinely offering TMS to patients following robust evidence from this study.

“These are important findings showing this novel technique can hugely benefit patients with severe depression which has not responded to other treatments."

The BRIGhTMIND trial was led by experts at the University of Nottingham. It was hosted by Nottinghamshire Healthcare NHS Foundation Trust.

The study was funded by the Efficacy and Mechanism Evaluation (EME) Programme - an NIHR and MRC partnership. NIHR’s Clinical Research Network also assisted with recruitment, recruiting more than 250 patients across England for the trial.

Reference:

Morriss, R., Briley, P.M., Webster, L. et al. Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial. Nat Med (2024). https://doi.org/10.1038/s41591-023-02764-z.