Transcranial Magnetic Stimulation for Psychological Distress in Patients With Advanced Illness

Psychological and existential distress are a common cause of suffering among patients nearing the end of life, and a major reason for requesting medical aid in dying. Existing treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. There is a need to develop scalable, brief, and rapidly effective therapeutic approaches that can reduce psychological and existential distress in patients nearing the end of life. Repetitive Transcranial Magnetic Stimulation is an effective treatment for refractory depression, and new protocols and increasing availability of rTMS may make this therapy feasible and acceptable for patients who suffer from psychological or existential distress near the end of life. Among patients with advanced illness followed by a PC provider, the study objectives are to: 1. Identify the lowest and range of therapeutic rTMS dose to relieve psychological distress, including an analysis of clinical predictors of response. 2. Test the feasibility and preliminary efficacy of rTMS for the treatment of psychological distress including: 1) ease of recruitment; 2) completion of follow-up; 3) effect size and variance estimates of treatment for primary and secondary outcomes; and 4) patient satisfaction with treatment. This study is a phase 2a dose-finding open-label clinical trial, followed by a phase 2b prospective, sham-control or sham-crossover study, depending on the therapeutic dose identified in phase 2a. The investigators will enroll eligible patients from an inpatient palliative care unit and administer rTMS according to established best practice international guidelines. Two screening tests will be conducted (one completed by patient and another by the treating physician) to ensure the patient has no contraindications to rTMS. In the open-label dose-finding study, investigators will determine the appropriate dose of treatment that leads to positive patient outcomes, assess characteristics associated with positive and rapid response to rTMS, and examine if this treatment is feasible and acceptable to patients by measuring rates of enrollment and completion of the treatment sessions. Based on results from this first phase, a phase 2b feasibility and preliminary efficacy randomized clinical trial will be conducted to measure the effect of rTMS by comparing patient symptoms before and after the rTMS intervention.