Repetitive Transcranial Magnetic Stimulation for People With Treatment-Resistant Depression: A Health Technology Assessment.

Background: Major depression is one of the most diagnosed mental illnesses in Canada. Generally, people are treated successfully with antidepressants or psychotherapy, but some people do not respond to these treatments (called treatment-resistant depression [TRD]). Repetitive transcranial magnetic stimulation (rTMS) delivers magnetic pulses to stimulate the areas of the brain associated with mood regulation. Several modalities of rTMS exist (e.g., high frequency rTMS, intermittent theta burst stimulation [iTBS], deep transcranial magnetic stimulation). We conducted a health technology assessment of rTMS for people with TRD, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding rTMS, and patient preferences and values.

Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias in Systematic Reviews (ROBIS) tool and Cochrane Risk of Bias for Randomized Controlled Trials and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 3-year horizon from a public payer perspective. We also analyzed the 5-year budget impact of publicly funding rTMS for people with TRD in Ontario. To assess the potential value of rTMS, we spoke with people who have TRD. Seven rTMS modalities were considered: low-frequency (1 Hz) stimulation, high-frequency (10-20 Hz) stimulation, unilateral stimulation, bilateral stimulation, iTBS, continuous theta burst stimulation, and deep transcranial magnetic stimulation.

Results: We included 58 primary studies, 9 systematic reviews, and 1 network meta-analysis in the clinical evidence review. Most rTMS modalities were more effective than sham treatment for all outcomes (GRADE: Moderate to High). All rTMS modalities were similar to one another in response and remission rates (GRADE: not reported) and were similar to electroconvulsive therapy (ECT) in response and remission rates (GRADE: Moderate). Moreover, in both the reference case and scenario analyses, two rTMS modalities (rTMS or iTBS), followed by ECT when patients did not respond to initial treatment, were less expensive and more effective than ECT alone. They were cost-effective compared with pharmacotherapy alone at a willingness-to-pay amount of $50,000 per quality-adjusted life-year (QALY). The annual budget impact of publicly funding rTMS would range from $9.3 million in year 1 to $15.76 million in year 5, for a total of $63.2 million over the next 5 years. People with TRD we spoke with reported that their experiences were generally favourable, and their attitudes toward rTMS were positive. Similarly, psychiatrists had positive attitudes toward and acceptance of rTMS. Our quantitative literature review on preferences revealed some gaps in psychiatrists' knowledge of rTMS, which could have been influenced by their level of training on rTMS.

Conclusions: Most rTMS modalities are likely more effective than sham rTMS on all outcomes. All rTMS modalities are similar to ECT and to one another in response and remission rates. Compared with ECT alone, two rTMS modalities (high-frequency rTMS and iTBS), followed by ECT when necessary in a stepped care pathway, were less costly and more effective for managing adults with TRD. These types of rTMS (high-frequency rTMS and iTBS) were cost-effective compared with pharmacotherapy alone at a willingness-to-pay amount of $50,000 per QALY. Publicly funding rTMS (high-frequency rTMS and iTBS) for the treatment of adults with TRD in Ontario over the next 5 years would add $63.2 million in total costs. People with TRD had positive experiences and attitudes toward rTMS.