Transcranial Magnetic Stimulation for psychological distress in patients with advanced illness: A phase 2a/2b dose-finding and feasibility clinical trial

In our study, we aimed to explore the potential of repetitive transcranial magnetic stimulation (rTMS; a treatment that delivers magnetic pulses to targeted regions of the scalp) as a treatment for psychological and existential distress in patients with advanced illness approaching the end of life. A significant proportion of these patients experience symptoms of depression and anxiety along with existential distress, impacting their quality of life. Given the safety and effectiveness of rTMS in treating mood and anxiety disorders, we investigated its use in the palliative care setting, using an accelerated rTMS protocol, which involved a shorter treatment duration of 5 days to hasten the time-to-effect. This approach, to the best of our knowledge, had not been previously explored for treating psychological and existential distress in this population.

The study took place at a single academic Palliative Care Unit in Ottawa, Ontario, recruiting participants from Bruyere Continuing Care Facilities, the Ottawa Hospital, and the Regional Palliative Consultation Team in Ottawa. We identified potential participants based on a set of inclusion criteria which included their Edmonton Symptom Assessment System (ESAS) scores and confirmation of psychological or existential distress using the Hamilton Depression Rating Scale (HDRS) and Demoralization Scale (DEM). Exclusion criteria included a diagnosed seizure disorder, documented brain lesions, contraindications to rTMS (e.g. intracranial metallic clips or plates), or an inability to remain still while sitting up (45 degrees) for the duration of therapy. Participant symptoms were assessed through the completion of the HDRS, Hospital Anxiety and Depression Scale (HADS), and three secondary measures before the start of treatment, during the five days of treatment, and two, four, and eight weeks from their final rTMS treatment day.

A total of 11 patients met the inclusion criteria and consented to participate in the study between November 2020 and June 2023. However, the research timeline was affected by delays and interruptions, primarily due to the challenges posed by the COVID-19 pandemic. Six participants completed the therapy. Results show a significant reduction in depression scores 2-weeks post-treatment, with five of six participants achieving remission of depression, anxiety, or both. In addition, four participants experienced a relief in existential distress symptoms 2-weeks post-treatment. The verbal reports from the participants were equally positive, supporting the effectiveness and tolerability of the rTMS intervention with no serious adverse events being observed. One participant stated, “I feel like a wall of depression has been lifted”, while another stated that she would get to be “a mother to [her] kids again”.

The use of rTMS in the palliative setting has historically faced barriers related to treatment duration and availability. However, our study demonstrates that accelerated rTMS protocols could be an appealing and effective therapeutic option for patients who are time-constrained and seeking rapid relief at the end of life.

Overall, the findings from our study supports the use of rTMS for managing existential distress in patients at the end of life, offering new hope for an effective, rapid, and acceptable treatment that can relieve their feelings of existential distress and suffering.