In a recent study published in the journal Nature Medicine, researchers presented groundbreaking findings in the treatment of depression, offering new insights into the effectiveness of two different brain stimulation techniques. The study, conducted across five centres, compared the impacts of connectivity-guided intermittent theta burst stimulation (cgiTBS) and repetitive transcranial magnetic stimulation (rTMS) on individuals with treatment-resistant depression.
The research involved 255 participants who underwent 20 sessions over 4–6 weeks of either cgiTBS or rTMS. The goal was to evaluate the efficacy of these treatments in reducing depression symptoms over 8, 16, and 26 weeks. Both treatments used MRI-neuronavigated technology, with cgiTBS targeting based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex, while rTMS was delivered at a standard stimulation site.
Lead author of the study, Dr Richard Morriss, professor of psychiatry at the University of Nottingham, said: “The key motivation was to try to extend the length of time that people receiving TMS would be substantially improved in terms of their depression symptoms in people who had not improved with other standard treatments for depression. We had talked to our patient and public involvement group of people suffering from chronic depression, some with experience with TMS.
“They told us that when you have suffered from depression for a long time, getting yourself organised to go to the hospital on a regular basis, sometimes at great cost, does not seem worth it for TMS if you are going to stay well for a month or three months. It is not long enough to make meaningful changes to their lives. We tried to find a way of increasing the length of time they remained well.”
The study’s primary outcome measured changes in the GRID Hamilton Depression Rating Scale 17-item score across the different time points. Interestingly, the results showed no significant difference between cgiTBS and rTMS in reducing depression symptoms. Both treatments demonstrated a persistent decrease in depressive symptoms over 26 weeks, with a similar trajectory of improvement.
Professor Morriss added: “To our surprise, we found that using functional MRI to personalise connectivity between these two brain regions and neuronavigation to ensure consistency of stimulation at the same site versus personalisation standard rTMS using structural MRI equally improved depression symptoms for up to 26 weeks after 20 TMS sessions. The changes were substantial, with improvements also in anxiety, thinking and memory, function, and quality of life.
“Improvements were substantially greater than with sham treatments, usually found in this patient group with antidepressants and psychological treatment available, and in terms of the brain areas affected on an MRI scan. While some of the benefits may be a sham effect or due to other treatments for depression, a lot of the response is likely to be a direct effect of TMS.”
One of the key aspects of this research was its focus on treatment-resistant depression, a condition where patients do not adequately respond to traditional treatments like antidepressants. The study’s findings are particularly relevant, as they suggest that both cgiTBS and rTMS could be equally effective alternatives for this challenging patient group.
Safety was also a critical aspect of the study, with close monitoring of adverse events. Two serious adverse events, possibly related to the treatments, were noted: mania and psychosis. However, these incidents were rare, and the treatments were generally well-tolerated by participants.
The study also explored secondary outcomes, including self-rated depression, anxiety, functioning, and quality of life measures. Improvements were noted in these areas as well, although again, no significant differences were observed between the two treatment groups.
An intriguing aspect of the research was the neuroimaging outcomes. The study aimed to determine if the initial connectivity between specific brain regions could predict clinical outcomes. While the primary neuroimaging hypothesis was not supported, the researchers observed that changes in the brain’s connectivity patterns were associated with improvements in depression.
Professor Morriss concluded: “We are carrying out further analysis of our results with additional scanning to learn more about the optimal ways of delivering TMS and we will soon publish our health economics results.”
The study’s results have significant implications for the treatment of depression, especially in cases resistant to conventional methods. They highlight the potential of brain stimulation techniques as viable alternatives, providing hope for many patients struggling with this debilitating condition.
This study marks a significant step forward in understanding and treating depression. It underscores the importance of personalised medicine and the need for continued research in this area to refine these techniques further and maximise their therapeutic potential.