Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials
Abstract
Background: Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs). Method: We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT). Results: Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant. Conclusions: HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.
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Most clinical rTMS treatments for MDD occur daily and are applied using scalp-based targeting of DLPFC; these standard treatments are only modestly effective, even in the general MDD population.
“Most clinical rTMS treatments for MDD occur daily (one rTMS session per day) and are applied using scalp-based targeting of DLPFC. These standard treatments are only modestly effective, even in the general MDD population (17, 24–31).”
Neurostimulatory treatments such as ECT, TMS, or deep brain stimulation can be effective to some extent, but none are 100% effective.
“Patients who fail repeated medication trials, hospitalisation, and psychotherapy sometimes go on to try neurostimulatory treatments, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or deep brain stimulation, all of which can be effective to some extent; but none are 100% effective.”
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McClintock, S. M., Reti, I. M., Carpenter, L. L., McDonald, W. M., Dubin, M., Taylor, S. F., Cook, I. A., O’Reardon, J., Husain, M. M., Wall, C., et al. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16cs10905 · Cited by 693 · see citing works
Perera, T., George, M. S., Grammer, G., Janicak, P. G., Pascual-Leone, A., & Wirecki, T. S. (2016) · Brain Stimulation · doi:10.1016/j.brs.2016.03.010 · Cited by 674 · see citing works
Peters, S. K., Dunlop, K., & Downar, J. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00104 · Cited by 611 · see citing works
“…characterized by hypofunctioning of the SN. Supportive meta-analyses are now available for rTMS in treating SUD (Gorelick et al., 2014; Dunlop et al., 2016), PTSD (Berlim and Van Den Eynde, 2014), bipolar disorder (McGirr et al., 2016) and OCD (Berlim et al., 2013a; Trevizol et al., 2016).”
BackgroundMethodMalhi, G. S., Bell, E., Bassett, D., Boyce, P., Bryant, R., Hazell, P., Hopwood, M., Lyndon, B., Mulder, R., Porter, R., et al. (2021) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867420979353 · Cited by 614 · see citing works
Milev, R. V., Giacobbe, P., Kennedy, S. H., Blumberger, D. M., Daskalakis, Z. J., Downar, J., Modirrousta, M., Patry, S., Vila-Rodriguez, F., Lam, R. W., et al. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716660033 · Cited by 586 · see citing works
Self-citationParikh, S. V., Quilty, L. C., Ravitz, P., Rosenbluth, M., Pavlova, B., Grigoriadis, S., Velyvis, V., Kennedy, S. H., Lam, R. W., MacQueen, G. M., et al. (2016) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716659418 · Cited by 562 · see citing works
<p>Management of Treatment-Resistant Depression: Challenges and Strategies</p>
Voineskos, D., Daskalakis, Z. J., & Blumberger, D. M. (2020) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s198774 · Cited by 446 · see citing works
Self-citationMutz, J., Vipulananthan, V., Carter, B., Hurlemann, R., Fu, C. H. Y., & Young, A. H. (2019) · BMJ · doi:10.1136/bmj.l1079 · Cited by 427 · see citing works
Brunoni, A. R., Moffa, A. H., Fregni, F., Palm, U., Padberg, F., Blumberger, D. M., Daskalakis, Z. J., Bennabi, D., Haffen, E., Alonzo, A., et al. (2016) · British Journal of Psychiatry · doi:10.1192/bjp.bp.115.164715 · Cited by 414 · see citing works
Self-citationGaynes, B. N., Lloyd, S. W., Lux, L., Gartlehner, G., Hansen, R. A., Brode, S., Jonas, D. E., Evans, T. S., Viswanathan, M., & Lohr, K. N. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13r08815 · Cited by 347 · see citing works
Mir-Moghtadaei, A., Caballero, R., Fried, P., Fox, M. D., Lee, K., Giacobbe, P., Daskalakis, Z. J., Blumberger, D. M., & Downar, J. (2015) · Brain Stimulation · doi:10.1016/j.brs.2015.05.008 · Cited by 269 · see citing works
Self-citationReinforcement learning in depression: a review of computational research
Chen, C., Takahashi, T., Nakagawa, S., Inoue, T., & Kusumi, I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.005 · Cited by 233 · see citing works
Fitzgerald, P. B., Hoy, K. E., Anderson, R. J., & Daskalakis, Z. J. (2016) · Depression and Anxiety · doi:10.1002/da.22503 · Cited by 204 · see citing works
Self-citationBauer, M., Severus, E., Köhler, S., Whybrow, P. C., Angst, J., Möller, H.-J., & on behalf of the Wfsbp Task Force on Treatment Guidelines for Unipolar Depressive Disorders (2015) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2014.1001786 · Cited by 199 · see citing works
Noninvasive brain stimulation treatments for addiction and major depression
Dunlop, K., Hanlon, C. A., & Downar, J. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12985 · Cited by 171 · see citing works
Bailey, N. W., Hoy, K. E., Rogasch, N. C., Thomson, R. H., McQueen, S., Elliot, D., Sullivan, C. M., Fulcher, B. D., Daskalakis, Z. J., & Fitzgerald, P. B. (2018) · Brain Stimulation · doi:10.1016/j.brs.2017.10.015 · Cited by 162 · see citing works
Self-citationMehler, D. M. A., Sokunbi, M. O., Habes, I., Barawi, K., Subramanian, L., Range, M., Evans, J., Hood, K., Lührs, M., Keedwell, P., et al. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0126-5 · Cited by 175 · see citing works
The neural crossroads of psychiatric illness: an emerging target for brain stimulation
Downar, J., Blumberger, D. M., & Daskalakis, Z. J. (2016) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.10.007 · Cited by 166 · see citing works
Self-citationDunlop, K., Woodside, B., Olmsted, M., Colton, P., Giacobbe, P., & Downar, J. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.292 · Cited by 147 · see citing works
Li, C., Chen, M., Lin, W., Hong, C., Yang, B., Liu, R., Tu, P., & Su, T. (2016) · Human Brain Mapping · doi:10.1002/hbm.23085 · Cited by 152 · see citing works
Rehn, S., Eslick, G. D., & Brakoulias, V. (2018) · Psychiatric Quarterly · doi:10.1007/s11126-018-9566-7 · Cited by 142 · see citing works
Non-pharmacological treatment of depression: a systematic review and evidence map
Farah, W. H., Alsawas, M., Mainou, M., Alahdab, F., Farah, M. H., Ahmed, A. T., Mohamed, E. A., Almasri, J., Gionfriddo, M. R., Castaneda-Guarderas, A., et al. (2016) · Evidence Based Medicine · doi:10.1136/ebmed-2016-110522 · Cited by 141 · see citing works
The Insula: A Brain Stimulation Target for the Treatment of Addiction
Ibrahim, C., Rubin-Kahana, D. S., Pushparaj, A., Musiol, M., Blumberger, D. M., Daskalakis, Z. J., Zangen, A., & Le Foll, B. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00720 · Cited by 133 · see citing works
Self-citationFeffer, K., Fettes, P., Giacobbe, P., Daskalakis, Z. J., Blumberger, D. M., & Downar, J. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2017.11.011 · Cited by 116 · see citing works
Self-citationMorriss, R., Briley, P. M., Webster, L., Abdelghani, M., Barber, S., Bates, P., Brookes, C., Hall, B., Ingram, L., Kurkar, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-023-02764-z · Cited by 122 · see citing works
Magnetic seizure therapy (MST) for major depressive disorder
Daskalakis, Z. J., Dimitrova, J., McClintock, S. M., Sun, Y., Voineskos, D., Rajji, T. K., Goldbloom, D. S., Wong, A. H. C., Knyahnytska, Y., Mulsant, B. H., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-019-0515-4 · Cited by 92 · see citing works
Self-citationBlumberger, D. M., Vila-Rodriguez, F., Wang, W., Knyahnytska, Y., Butterfield, M., Noda, Y., Yariv, S., Isserles, M., Voineskos, D., Ainsworth, N. J., et al. (2021) · Brain Stimulation · doi:10.1016/j.brs.2021.09.003 · Cited by 81 · see citing works
Self-citationMartin, D. M., McClintock, S. M., Forster, J., & Loo, C. K. (2016) · Neuropsychology Review · doi:10.1007/s11065-016-9325-1 · Cited by 76 · see citing works
Cook (2014) · doi:10.1016/j.nec.2013.10.002 · Cited by 69 · see citing works
Treatment for Substance Use Disorder with Co-Occurring Mental Illness
Iqbal, M. N., Levin, C. J., & Levin, F. R. (2019) · Focus · doi:10.1176/appi.focus.20180042 · Cited by 66 · see citing works
Dembo, J., Schuklenk, U., & Reggler, J. (2018) · The Canadian Journal of Psychiatry · doi:10.1177/0706743718766055 · Cited by 60 · see citing works
Brini, S., Brudasca, N. I., Hodkinson, A., Kaluzinska, K., Wach, A., Storman, D., Prokop-Dorner, A., Jemioło, P., & Bala, M. M. (2023) · Clinical Psychology Review · doi:10.1016/j.cpr.2022.102236 · Cited by 44 · see citing works
Qiu, H., Liang, K., Lu, L., Gao, Y., Li, H., Hu, X., Xing, H., Huang, X., & Gong, Q. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.09.060 · Cited by 41 · see citing works
Magavi, L. R., Reti, I. M., & Vasa, R. A. (2017) · International Review of Psychiatry · doi:10.1080/09540261.2017.1300574 · Cited by 41 · see citing works
Kearney-Ramos, T. E., Dowdle, L. T., Mithoefer, O. J., Devries, W., George, M. S., & Hanlon, C. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00317 · Cited by 37 · see citing works
Internet-Based Self-help Interventions for Depression in Routine Care
Ebert, D. D., & Baumeister, H. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.1394 · Cited by 29 · see citing works
Tovar-Perdomo, S., McGirr, A., Van den Eynde, F., Rodrigues dos Santos, N., & Berlim, M. T. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.03.075 · Cited by 18 · see citing works
Self-citationKirk, M. A., Pirbaglou, M., Weerasekera, R., & Ritvo, P. (2022) · International Journal of Mental Health · doi:10.1080/00207411.2021.1959807 · Cited by 10 · see citing works
Oberman, L. M., Penafiel, A. I., Dieterich, R., Phan, C. T., Chou, Y.-Y., Pham, D. L., Adamson, M. M., Hines, C. E., Rezaee, Z., Deng, Z.-D., et al. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1605157
- Authors
- Berlim, M. T., van den Eynde, F., Tovar-Perdomo, S., & Daskalakis, Z. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Berlim, M. T.
- ORCID
- Daskalakis, Z. J.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-03-18
- Volume
- 44
- Issue
- 2
- Pages
- 225-239
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- OpenAlex
- W2143805083
- Cited by
- 620
- References
- 95
- Citations by year
- 2026: 36 · 2025: 62 · 2024: 48 · 2023: 52 · 2022: 47 · 2021: 64 · 2020: 49 · 2019: 63 · 2018: 49 · 2017: 41 · 2016: 41 · 2015: 34 · 2014: 26 · 2013: 6 · 2012: 1
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- high-frequency repetitive transcranial magnetic stimulation, major depressive disorder, antidepressant efficacy, response rate, remission rate, dropout rates, treatment tolerability, bipolar depression, stimulation parameters
- MeSH terms
- Major Depressive Disorder, Double-Blind Method, Humans, Remission Induction, Randomized Controlled Trials as Topic, Treatment Outcome, Transcranial Magnetic Stimulation
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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