Progressive decline in resting motor threshold during repetitive transcranial magnetic stimulation for depression: A naturalistic retrospective study.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) intensity is dosed relative to the resting motor threshold (rMT), yet longitudinal changes of rMT in real-world, medicated patients during treatment remain poorly characterized. We examined the trajectory of rMT during rTMS for depression and its clinical and pharmacological correlates. METHODS: In this naturalistic retrospective study, 130 adults with depression received rTMS, with rMT measured at every treatment session. Primary linear mixed models analyzed rMT at sessions 1, 5, 10, and 15, aligned with clinical and medication assessments; complementary models used all available daily measurements. Response was defined as a ≥50% reduction in the 17-item Hamilton Depression Rating Scale score at the last available post-baseline assessment. RESULTS: rMT declined progressively during treatment, reaching a 2.70 percentage-point reduction of maximal stimulator output by session 15 (p = 0.001). The rMT trajectory did not differ significantly according to treatment response, stimulation device, stimulation side, or rMT measurement method. The decline remained significant after adjustment for concurrent depressive and anxiety symptom severity. Higher concurrent BZRA doses were associated with higher overall rMT (p = 0.019), but its relation to trajectory was outlier-sensitive. Although the mean reduction was modest, a growing proportion of patients showed downward rMT drift over time. CONCLUSIONS: rMT decreased progressively during rTMS treatment for depression, independent of clinical response. Concurrent BZRA dose was associated with higher rMT, whereas its relationship with longitudinal change remained uncertain. The decline, together with marked inter-individual variability, supports regular rMT reassessment during treatment to maintain intended stimulation intensity.