[Published February 13, 2017 | Updated May 18, 2026]
Research on the effectiveness of TMS for depression continues to evolve.
As additional TMS devices and treatment protocols have been developed, researchers have examined whether newer approaches may offer advantages over the original forms of treatment. Questions have also been raised about whether terms such as “deep TMS,” “accelerated TMS,” and “theta burst stimulation” represent clinically meaningful differences, shorter or more convenient treatment protocols, or primarily marketing distinctions.
A major review article published in JAMA Psychiatry evaluated the available evidence regarding several alternatives to the original TMS protocol used for depression. The review remains one of the more comprehensive assessments of the scientific literature on TMS for major depressive episodes at the time it was published.
The review examined 81 studies comparing active TMS treatment with sham TMS in patients with depression. Most of the studies included patients with treatment-resistant depression and evaluated TMS as an add-on therapy rather than as a stand-alone treatment.
Researchers analyzed several different approaches to TMS delivery:
- High Frequency 10 Hz Stimulation of the Left Dorsolateral Prefrontal Cortex DLPFC.
- This was the original TMS protocol cleared by the FDA for major depression and is the best-established conventional protocol. Treatment is typically delivered to the left DLPFC using high-frequency stimulation.
- Low Frequency 1 Hz Stimulation of the Right DLPFC.
- This alternative approach was developed based on observations that right- and left-sided stimulation, as well as low- and high-frequency stimulation, may produce differing neurophysiological effects. Low-frequency right-sided stimulation has often been studied in patients with depression accompanied by significant anxiety symptoms.
- Bilateral Stimulation.
- This approach combines high-frequency left-sided stimulation with low-frequency right-sided stimulation during the same treatment course or session.
- Deep or H-Coil TMS.
- Deep TMS uses a different coil design intended to stimulate broader and deeper cortical regions than a conventional figure-eight coil. Earlier reviews found that evidence for deep TMS was less extensive than for conventional left-sided high-frequency rTMS. Since then, additional randomized and naturalistic studies have supported the efficacy of H-coil deep TMS for major depression, although current evidence does not clearly establish that deep TMS is superior to conventional figure-eight coil TMS for depression.
- Theta Burst Stimulation TBS.
- Theta burst protocols were developed to shorten treatment times and potentially engage neuroplasticity-related mechanisms. Intermittent theta burst stimulation, or iTBS, can be delivered in approximately 3 minutes, compared with approximately 37.5 minutes for a standard 10 Hz rTMS session. In the large THREE-D randomized non-inferiority trial, iTBS was found to be non-inferior to standard 10 Hz left-sided rTMS for treatment-resistant depression. iTBS was cleared by the FDA for major depression in 2018, and newer guidelines now consider it an established first-line rTMS protocol for treatment-resistant depression.
- Low-Field Synchronized TMS.
- This method attempts to synchronize stimulation with an individual’s alpha brain-wave frequency. The 2017 network meta-analysis did not find synchronized TMS to be more effective than sham treatment, and it remains less established than conventional rTMS or iTBS.
- Priming TMS.
- This approach involves delivering high-frequency stimulation before low-frequency stimulation in an effort to enhance treatment response. In the 2017 network meta-analysis, priming low-frequency rTMS was among the interventions found to be more effective than sham, although it has not become as commonly used in routine clinical practice as left-sided high-frequency rTMS, right-sided low-frequency rTMS, bilateral rTMS, or iTBS.
The authors used two different methods to compare effectiveness. One method directly analyzed head-to-head comparisons within individual studies, while the second used network meta-analysis to compare results across trials.
In direct comparisons, several approaches were found to be more effective than sham TMS:
- Bilateral High Frequency TMS — Odds Ratio 3.96, 95% confidence interval 2.37–6.60.
- Left-Sided High Frequency TMS — Odds Ratio 3.07, 95% confidence interval 2.24–4.41.
- Right-Sided Low Frequency TMS — Odds Ratio 2.37, 95% confidence interval 1.52–3.68.
The network analysis odds ratios of remission or response and the confidence intervals are graphed below.
The authors concluded:
“The interventions more effective than sham were priming low-frequency, bilateral, high-frequency, theta-burst stimulation, and low-frequency rTMS. Novel rTMS interventions accelerated, synchronized, and deep rTMS were not more effective than sham.”
Overall, the findings suggested that several established TMS approaches demonstrated benefit in treating depression, while evidence supporting some newer techniques, including accelerated, synchronized, and deep TMS protocols, remained limited at the time of publication.
Since that 2017 review, the evidence base has continued to expand. The most important change has been the strengthening of evidence for intermittent theta burst stimulation. The THREE-D trial showed that iTBS was non-inferior to standard 10 Hz rTMS while requiring a much shorter treatment session. As a result, iTBS is now commonly considered a clinically established TMS protocol rather than an experimental alternative.
Recent guidelines reflect this shift. The CANMAT 2023 depression guidelines identify rTMS as a first-line neuromodulation treatment for treatment-resistant depression and list several first-line rTMS protocols, including intermittent theta burst stimulation to the left DLPFC, high-frequency rTMS to the left DLPFC, and low-frequency rTMS to the right DLPFC.
A 2025 comprehensive consensus update, endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology, also concluded that TMS has substantial evidence supporting its safety and efficacy for depressive disorders. The consensus update notes that newer protocols, especially iTBS, have improved treatment efficiency while maintaining antidepressant efficacy.
Accelerated TMS protocols have also received growing attention. These approaches deliver multiple TMS or iTBS sessions per day, attempting to compress treatment into days rather than weeks. Early studies of Stanford Neuromodulation Therapy, previously called SAINT, reported high remission rates in highly treatment-resistant depression using an intensive, individualized accelerated iTBS protocol. However, accelerated approaches vary substantially in targeting method, dose, number of sessions, intersession interval, and total treatment duration. Current evidence is promising, but these protocols are not yet as well established as standard daily rTMS or standard iTBS.
The interpretation of deep TMS has also become more nuanced. The 2017 JAMA Psychiatry network meta-analysis did not find deep TMS to be significantly more effective than sham in that particular analysis. However, later and additional evidence, including randomized controlled and large naturalistic studies, supports H-coil deep TMS as an effective treatment for major depression. The more balanced conclusion is that deep TMS appears to be an evidence-supported treatment option, but the literature does not clearly show that it is superior to conventional figure-eight coil TMS for depression.
Taken together, the updated literature supports the main conclusion of the earlier review while adding several important refinements. Conventional left-sided high-frequency rTMS, right-sided low-frequency rTMS, bilateral rTMS, and iTBS all have meaningful evidence supporting their use in depression. iTBS now has particularly strong support because it appears to offer similar efficacy to standard 10 Hz rTMS with much shorter treatment sessions. Deep TMS and accelerated TMS are reasonable areas of clinical and research interest, but claims of superiority over standard TMS should be made cautiously.
For patients, the practical message is that TMS is not a single treatment protocol but a family of related neuromodulation approaches. The best-supported protocols remain those targeting the dorsolateral prefrontal cortex using conventional high-frequency left-sided stimulation, low-frequency right-sided stimulation, bilateral approaches, or intermittent theta burst stimulation. Newer protocols may improve convenience or access, but the strongest evidence continues to favor established TMS methods rather than assuming that newer terminology necessarily means greater effectiveness.
References
Brunoni, Andre R., Chaimani, Anna, Moffa, Adriano H., Razza, Laís B., Gattaz, Wagner F., Daskalakis, Zafiris J., and Carvalho, André F. Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. JAMA Psychiatry, Volume 74, Issue 2, 2017, pp. 143–152. doi:10.1001/jamapsychiatry.2016.3644.
Blumberger, Daniel M., Vila-Rodriguez, Fidel, Thorpe, Kevin E., et al. Effectiveness of Theta Burst Versus High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Depression THREE-D: A Randomised Non-Inferiority Trial. The Lancet, Volume 391, Issue 10131, 2018, pp. 1683–1692.
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.
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.
Levkovitz, Yechiel, Isserles, Moshe, Padberg, Frank, et al. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Major Depression: A Prospective Multicenter Randomized Controlled Trial. World Psychiatry, Volume 14, Issue 1, 2015, pp. 64–73.
Roth, Yiftach, Tendler, Aron, Arikan, M. Kemal, et al. Deep TMS H1 Coil Treatment for Depression: Results From a Large Post-Marketing Data Set. Psychiatry Research, 2023.
Clinical TMS Society. Updated Theta Burst Statement. 2024.
Lan, Xian-Jun, Cai, Dong-Bin, Liu, Qi-Man, et al. Stanford Neuromodulation Therapy for Treatment-Resistant Depression: A Systematic Review. Frontiers in Psychiatry, 2023.