In the April 2016 edition of Brain Stimulation, the Clinical TMS Society published expert consensus guidelines on the use of TMS. This review of the literature summarizes current evidence as well as areas of ongoing uncertainty regarding the use of TMS in the treatment of depression.
The process of developing the guideline is described in the introduction to the article:
“This consensus review was written by Clinical TMS Society leaders, informed by membership polls, and approved by the governing board. It summarizes current evidence for the safety and efficacy of TMS therapy for treating depression in routine clinical practice. Authors systematically reviewed published TMS antidepressant therapy clinical trials. Studies were then assessed and graded on their strength of evidence using the Levels of Evidence framework published by the University of Oxford Centre for Evidence Based Medicine.”
Since publication of the 2016 Clinical TMS Society consensus review, additional guidelines and reviews have strengthened the evidence base for TMS in major depressive disorder. A 2025 comprehensive consensus update, endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology, reviewed literature published after the original consensus statement and concluded that TMS continues to have substantial evidence supporting its safety and efficacy in depressive disorders. The update also notes that newer protocols, including intermittent theta burst stimulation, can reduce treatment time while maintaining antidepressant efficacy.
Similarly, the CANMAT 2023 depression guidelines identify rTMS as a first-line neuromodulation treatment for treatment-resistant depression after inadequate response to first-line psychotherapy and medication treatments. CANMAT lists intermittent theta burst stimulation to the left dorsolateral prefrontal cortex, high-frequency rTMS to the left dorsolateral prefrontal cortex, and low-frequency rTMS to the right dorsolateral prefrontal cortex as first-line rTMS protocols.
One commonly discussed topic in the literature is the durability of response following TMS treatment. Long-term outcome studies remain more limited than acute-treatment studies, both for TMS and for many antidepressant treatments in general. However, the available research suggests that a meaningful proportion of patients who respond positively to TMS continue to experience benefit for months after the acute treatment course ends.
In a systematic review and meta-analysis of durability studies, Senova and colleagues found that among patients who responded to an acute course of rTMS, approximately 66.5% sustained response at 3 months, 52.9% at 6 months, and 46.3% at 12 months. The authors concluded that rTMS appears to have clinically meaningful durability for many patients, while also noting that maintenance strategies may improve durability for some patients.
This durability profile is clinically relevant when comparing TMS with ketamine-based treatments. Ketamine and esketamine can produce rapid antidepressant effects, sometimes within hours or days, but the response is often less durable after treatment is discontinued. A systematic review of maintenance ketamine treatment noted that ketamine has rapid but often transient antidepressant effects, and that ongoing maintenance strategies are commonly studied because benefit may fade after acute treatment ends.
Esketamine relapse-prevention data also support this distinction. In a randomized withdrawal trial of patients with treatment-resistant depression who had responded to esketamine plus an oral antidepressant, patients who continued esketamine had a significantly delayed time to relapse compared with those switched to placebo nasal spray while continuing the oral antidepressant. Among stable remitters, relapse occurred in 26.7% of patients who continued esketamine versus 45.3% of those switched to placebo nasal spray; among stable responders who had not achieved remission, relapse occurred in 25.8% versus 57.6%, respectively.
Taken together, the available evidence suggests an important practical difference: ketamine and esketamine responses more often appear to depend on continued intermittent maintenance treatment, whereas TMS is commonly delivered as a time-limited acute course, with many responders maintaining benefit for months afterward. This does not mean that TMS response is always permanent. A substantial minority of patients relapse after TMS and may benefit from booster or repeat treatment. However, the durability literature is consistent with the clinical observation that, among responders, TMS may have a more sustained post-treatment benefit than ketamine when ongoing treatment is stopped.
Questions remain regarding outcomes beyond the first year, optimal maintenance schedules, patient selection, and the comparative durability of TMS versus ketamine-based treatments. Direct long-term head-to-head studies comparing TMS with ketamine or esketamine remain limited. For this reason, it is most accurate to say that the current evidence is consistent with greater post-treatment durability after TMS response, rather than that this has been definitively proven in large long-term comparative trials.
The guideline authors also note the challenges associated with follow-up research, stating that:
“Durability studies struggle with a selection bias since with patients lost to follow up, it is unclear if they are well and no longer need treatment, or if they have worsened and started other treatments.”
References
Perera, Tarique, et al. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimulation, Volume 9, Issue 3, 2016, pp. 336–346.
Trapp, Nicholas T., et al. Consensus Review and Considerations on TMS to Treat Depression: A Comprehensive Update Endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology. Clinical Neurophysiology, Volume 170, 2025, pp. 206–233.
Lam, Raymond W., et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults. The Canadian Journal of Psychiatry, 2024.
Senova, Suhan, et al. Durability of Antidepressant Response to Repetitive Transcranial Magnetic Stimulation: Systematic Review and Meta-Analysis. Brain Stimulation, Volume 12, Issue 1, 2019, pp. 119–128.
Strong, Christopher E., et al. Maintenance Ketamine Treatment for Depression: A Systematic Review of Efficacy, Safety, and Tolerability. The Lancet Psychiatry, Volume 9, Issue 11, 2022, pp. 907–921.
Daly, Ella J., et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry, Volume 76, Issue 9, 2019, pp. 893–903.
Noda, Yoshihiro, et al. Repetitive Transcranial Magnetic Stimulation as Maintenance Treatment of Depression: The MAINT-R Randomized Clinical Trial. JAMA Network Open, 2025.