Clinical effectiveness of switching to right lateral orbitofrontal cortex-TMS after failure of sequential bilateral dorsolateral prefrontal-TMS in major depression

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Background When patients with major depression fail to respond to TMS using a conventional dorsolateral prefrontal cortex (DLPFC) protocol, several published case series have suggested that switching to or adding-on 1Hz right lateral orbitofrontal cortex (R-LOFC) TMS may succeed. However, many of these case series are hampered by relatively short courses of treatment (i.e., <25 sessions) for either the DLPFC, the R-LOFC, or both protocols. Methods Here we report clinical outcomes for a case series of N=54 patients in a community setting who underwent a full course of 36 sessions of sequential bilateral (SBL) DLPFC-TMS (right/left, 1Hz/20Hz, 60s on 30s off/2s on 4s off, 360 pulses/1200 pulses, both 120% RMT) without response, then completed a full course of another 36 sessions of 1 Hz-R-LOFC-TMS (1Hz, 60s on 30s off, 360 pulses). Results Following the R-LOFC course, 15/54 (27.8%) achieved response and 9/54 (16.7%) achieved remission on PHQ-9, with a mean score improving from 14.2±4.1 to 9.5±5.3 points. Responders showed a distinctive discontinuity in response trajectory immediately following the switch from DLPFC to R-LOFC, with a significant sharp drop in symptoms suggesting causal effect. Conclusion Switching to 1 Hz-R-LOFC-TMS yields a sharp change in response trajectory in a subset of SBL-DLPFC-TMS unresponsive patients, implying a distinctive therapeutic mechanism rather than the accumulative effects of additional sessions. Future randomized controlled studies may establish definitive efficacy for 1 Hz-R-LOFC-TMS in depression among non-responders to conventional DLPFC-TMS.