Trajectory of changes in depressive symptoms after acute repetitive transcranial magnetic stimulation: A meta-analysis of follow-up effects

Background: The follow-up effect after acute repetitive transcranial magnetic stimulation (rTMS) for major depressive episodes remains unclear. Furthermore, the benefits of maintenance rTMS are poorly understood. Aim: To investigate the trajectory of changes in depressive symptoms after acute rTMS and effects of maintenance rTMS during this period. Method: This meta-analysis (PROSPERO: CRD42022374077) searched major databases up to October 1, 2022. Treatment outcome was depressive scores collected at least 3 months after the end of an acute rTMS course for depression. We extracted data at different time points after acute rTMS and categorized by whether maintenance rTMS was performed. A single-stage random-effects dose-response meta-analysis was undertaken to model the nonlinear relationships. Effect sizes were calculated as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: 24 eligible studies comprising 911 total patients—225 of whom received maintenance rTMS—were included. Maintenance rTMS contributed to relative stability in patients' mood symptoms during the first 5 months (SMD [95% CI]: 3rd month, −0.10 [−0.30 to 0.10]; 5th month, 0.00 [−0.55 to 0.55]), with heterogeneity characterized as low to moderate. Further analysis revealed that maintenance rTMS performed monthly or more frequently provided sustained benefits for up to 6–12 months. Conversely, patients without maintenance rTMS had moderate to high heterogeneity, although the change in mean mood symptom scores during the 12-month follow-up was also minor (6th month, 0.03 [−0.51 to 0.56]; 12th month, 0.10 [−0.59 to 0.79]). Conclusion: Maintenance rTMS might keep patients' mood relatively stable for up to 5 months after acute rTMS. Monthly or more frequent maintenance rTMS offers greater benefits.