BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) can be delivered in 3 min and has demonstrated comparable effectiveness to the conventional 37.5 min 10Hz rTMS protocol in patients with depression.ObjectivesTo compare the direct treatment costs per course and per remission for iTBS compared to 10Hz rTMS treatment in depression.MethodsWe conducted a cost analysis from a healthcare system perspective using patient-level data from a large randomized non-inferiority trial (THREE-D). Depressed adults 18 to 65 received either 10Hz rTMS or iTBS treatment. Treatment costs were calculated using direct healthcare costs associated with equipment, coils, physician assessments and technician time over the course of treatment. Cost per remission was estimated using the proportion of patients achieving remission following treatment. Deterministic sensitivity analyses and non-parametric bootstrapping was used to estimate uncertainty.ResultsFrom a healthcare system perspective, the average cost per patient was USD$1,108 (SD 166) for a course of iTBS and $1,844 (SD 304) for 10Hz rTMS, with an incremental net savings of $735 (95% CI 688 to 783). The average cost per remission was $3,695 (SD 552) for iTBS and $6,146 (SD 1,015) for 10Hz rTMS, with an average incremental net savings of $2,451 (95% CI 2,293 to 2,610).ConclusionsThe shorter session durations and treatment capacity increase associated with 3 min iTBS translate into significant cost-savings per patient and per remission when compared to 10Hz rTMS.

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Non-invasive brain stimulation (NIBS) is emerging as a robust treatment alternative for major depressive disorder, with a potential for achieving higher remission rates by providing targeted stimulation to underlying brain networks, such as the salience network (SN). Growing evidence suggests that these therapeutic effects are dependent on the frequency and phase synchrony between SN oscillations and stimulation as well as the task-specific state of the SN during stimulation. However, the development of phase-synchronized non-invasive stimulation has proved challenging until recently. Here, we use a phase-locked pulsed brain stimulation approach to study the effects of two NIBS methods: transcranial alternating current stimulation (tACS) versus phase-locked transcranial pulsed current stimulation (tPCS), on the SN during an SN activating task. 20 healthy volunteers participated in the study. Each volunteer partook in four sessions, receiving one stimulation type at random (theta-tACS, peak tPCS, trough tPCS or sham) while undergoing a learning game, followed by an unstimulated test based on learned material. Each session lasted approximately 1.5 h, with an interval of at least 2 days to allow for washout and to avoid cross-over effects. Our results showed no statistically significant effect of stimulation on the event related potential (ERP) recordings, resting electroencephalogram (EEG), and the performance of the volunteers. While stimulation effects were not apparent in this study, the nominal performance of the phase-locking algorithm offers a technical foundation for further research in determining effective stimulation paradigms and conditions. Specifically, future work should investigate stronger stimulation and true task-specific stimulation of SN nodes responsible for the task as well as their recording. If refined, NIBS could offer an effective, homebased treatment option.

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