TITLE: Transcranial Magnetic Stimulation Therapy for Patients with Refractory
Depression: Clinical-Effectiveness and Guidelines
DATE: 14 April 2009
1. What is the clinical-effectiveness of transcranial magnetic stimulation therapy for patients
with refractory depression?
2. What are the guidelines for using transcranial magnetic stimulation therapy for patients
with refractory depression?
A limited literature search was conducted on key health technology assessment resources,
including PubMed, the Cochrane Library (Issue 1, 2009), University of York Centre for Reviews
and Dissemination (CRD) databases, ECRI, EuroScan, international HTA agencies, and a
focused Internet search. Results include articles published between 2004 and April 2009, and
are limited to English language publications only. No filters were applied to limit the retrieval by
study type. Internet links are provided, where available.
HTIS reports are organized so that the higher quality evidence is presented first. Therefore,
health technology assessment reports, systematic reviews, and meta-analyses are presented
first. These are followed by randomized controlled trials (RCTs), controlled clinical trials,
observational studies, and evidence-based guidelines.
One health technology assessment, three systematic reviews, 13 RCTs, three controlled clinical
trials, eight observational studies, and two evidence-based guidelines were identified pertaining
to the use of transcranial magnetic stimulation therapy for patients with refractory depression.
Additional information that may be of interest has been included in the appendix.
Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing
health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews.
The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts
within the time allowed. HTIS responses should be considered along with other types of information and health care considerations.
The information included in this response is not intended to replace professional medical advice, nor should it be construed as a
recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality
evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for
which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation
of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect.
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Health technology assessments
1. Repetitive transcranial magnetic stimulation as a treatment for major depression
[technology assessment report]. Canberra, Australia: Medical Services Advisory
Committee (MSAC); 2007.
09 Apr 2009)
09 Apr 2009)
Systematic reviews and meta-analyses
2. Schutter DJ. Antidepressant efficacy of high-frequency transcranial magnetic stimulation
over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a
meta-analysis. Psychol Med 2009;39(1):65-75. PubMed: PM18447962
3. Lam RW, Chan P, Wilkins-Ho M, Yatham LN. Repetitive transcranial magnetic stimulation
for treatment-resistant depression: a systematic review and metaanalysis. Can J
Psychiatry 2008;53(9):621-31. PubMed: PM18801225
4. Couturier JL. Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the
treatment of depression: a systematic review and meta-analysis. Journal of Psychiatry and
Neuroscience 2005; 30(2): 83-90; 2009.
(accessed 09 Apr 2009)
Structured abstract available with subscription at: http://www.cochrane.org
Randomized controlled trials
5. Bares M, Kopecek M, Novak T, Stopkova P, Sos P, Kozeny J, et al. Low frequency (1-Hz),
right prefrontal repetitive transcranial magnetic stimulation (rTMS) compared with
venlafaxine ER in the treatment of resistant depression: A double-blind, single-centre,
randomized study. J Affect Disord 2009. PubMed: PM19249105
6. Bretlau LG, Lunde M, Lindberg L, Unden M, Dissing S, Bech P. Repetitive transcranial
magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-
resistant major depression: a double-blind, randomised, sham-controlled trial.
Pharmacopsychiatry 2008;41(2):41-7. PubMed: PM18311683
7. McLoughlin DM, Mogg A, Eranti S, Pluck G, Purvis R, Edwards D, et al. The Clinical
effectiveness and cost of repetitive transcranial magnetic stimulation versus
electroconvulsive therapy in severe depression: a multicentre pragmatic randomised
controlled trial and economic analysis. Health Technology Assessment 2007;11(24).
Summary and full-text available:
http://www.ncchta.org/execsumm/summ1124.shtml (accessed 14 Apr 2009)
Transcranial Magnetic Stimulation Therapy for Patients with Refractory Depression 2
8. O'Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, et al.
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major
depression: a multisite randomized controlled trial. Biol Psychiatry 2007;62(11):1208-16.
9. Avery DH, Holtzheimer PE, III, Fawaz W, Russo J, Neumaier J, Dunner DL, et al. A
controlled study of repetitive transcranial magnetic stimulation in medication-resistant
major depression. Biol Psychiatry 2006;59(2):187-94. PubMed: PM16139808
10. Fitzgerald PB, Huntsman S, Gunewardene R, Kulkarni J, Daskalakis ZJ. A randomized
trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as
augmentation in treatment-resistant major depression. Int J Neuropsychopharmacol
2006;9(6):655-66. PubMed: PM16959055
11. Fitzgerald PB, Benitez J, de Castella A, Daskalakis ZJ, Brown TL, Kulkarni J.
A randomized, controlled trial of sequential bilateral repetitive transcranial magnetic
stimulation for treatment-resistant depression. Am J Psychiatry 2006;163(1):88-94.
12. McDonald WM, Easley K, Byrd EH, Holtzheimer P, Tuohy S, Woodard JL, et al.
Combination rapid transcranial magnetic stimulation in treatment refractory depression.
Neuropsychiatr Dis Treat 2006;2(1):85-94.
13. Rosa MA, Gattaz WF, Pascual-Leone A, Fregni F, Rosa MO, Rumi DO, et al. Comparison
of repetitive transcranial magnetic stimulation and electroconvulsive therapy in unipolar
non-psychotic refractory depression: a randomized, single-blind study.
Int J Neuropsychopharmacol 2006;9(6):667-76. PubMed: PM16923322
14. Rossini D, Lucca A, Zanardi R, Magri L, Smeraldi E. Transcranial magnetic stimulation in
treatment-resistant depressed patients: a double-blind, placebo-controlled trial. Psychiatry
Res 2005;137(1-2):1-10. PubMed: PM16225930
15. Su TP, Huang CC, Wei IH. Add-on rTMS for medication-resistant depression: a
randomized, double-blind, sham-controlled trial in Chinese patients. J Clin Psychiatry
2005;66(7):930-7. PubMed: PM16013911
16. Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, et al. Repetitive
transcranial magnetic stimulation: a putative add-on treatment for major depression in
elderly patients. Psychiatry Res 2004;126(2):123-33. PubMed: PM15123391
17. Poulet E, Brunelin J, Boeuve C, Lerond J, D'Amato T, Dalery J, et al. Repetitive
transcranial magnetic stimulation does not potentiate antidepressant treatment.
Eur Psychiatry 2004;19(6):382-3. PubMed: PM15363481
Controlled clinical trials
18. Vanderhasselt MA, De RR, Leyman L, Baeken C. Acute effects of repetitive transcranial
magnetic stimulation on attentional control are related to antidepressant outcomes.
J Psychiatry Neurosci 2009;34(2):119-26. PubMed: PM19270762
Transcranial Magnetic Stimulation Therapy for Patients with Refractory Depression 3
19. Loo CK, Mitchell PB, McFarquhar TF, Malhi GS, Sachdev PS. A sham-controlled trial of
the efficacy and safety of twice-daily rTMS in major depression. Psychol Med
2007;37(3):341-9. PubMed: PM17176505
20. Kauffmann CD, Cheema MA, Miller BE. Slow right prefrontal transcranial magnetic
stimulation as a treatment for medication-resistant depression: a double-blind, placebo-
controlled study. Depress Anxiety 2004;19(1):59-62. PubMed: PM14978787
21. Cohen RB, Boggio PS, Fregni F. Risk factors for relapse after remission with repetitive
transcranial magnetic stimulation for the treatment of depression. Depress Anxiety 2009.
22. Avery DH, Isenberg KE, Sampson SM, Janicak PG, Lisanby SH, Maixner DF, et al.
Transcranial magnetic stimulation in the acute treatment of major depressive disorder:
clinical response in an open-label extension trial. J Clin Psychiatry 2008;69(3):441-51.
23. Bloch Y, Grisaru N, Harel EV, Beitler G, Faivel N, Ratzoni G, et al. Repetitive transcranial
magnetic stimulation in the treatment of depression in adolescents: an open-label study.
J ECT 2008;24(2):156-9. PubMed: PM18580562
24. Demirtas-Tatlidede A, Mechanic-Hamilton D, Press DZ, Pearlman C, Stern WM, Thall M,
et al. An open-label, prospective study of repetitive transcranial magnetic stimulation
(rTMS) in the long-term treatment of refractory depression: reproducibility and duration of
the antidepressant effect in medication-free patients. J Clin Psychiatry 2008;69(6):930-4.
25. Abraham G, Milev R, Lazowski L, Jokic R, du TR, Lowe A. Repetitive transcranial
magnetic stimulation for treatment of elderly patients with depression - an open label trial.
Neuropsychiatr Dis Treat 2007;3(6):919-24. PubMed: PM19300628
26. Huang CC, Su TP, Wei IH. Repetitive transcranial magnetic stimulation for treating
medication-resistant depression in Taiwan: a preliminary study. J Chin Med Assoc
2005;68(5):210-5. PubMed: PM15909725
27. Schulze-Rauschenbach SC, Harms U, Schlaepfer TE, Maier W, Falkai P, Wagner M.
Distinctive neurocognitive effects of repetitive transcranial magnetic stimulation and
electroconvulsive therapy in major depression. Br J Psychiatry 2005;186:410-6. PubMed:
28. Nahas Z, Li X, Kozel FA, Mirzki D, Memon M, Miller K, et al. Safety and benefits of
distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75
years of age: a pilot study. Depress Anxiety 2004;19(4):249-56. PubMed: PM15274174
Guidelines and recommendations
29. Transcranial magnetic stimulation for severe depression [interventional procedure
guidance 242]. London: National Institute for Health and Clinical Excellence (NICE); 2007.
http://www.nice.org.uk/nicemedia/pdf/IPG242GUIDANCE.pdf (accessed 09 Apr 2009)
Transcranial Magnetic Stimulation Therapy for Patients with Refractory Depression 4
30. Major depression in adults in primary care. Bloomington (MN): Institute for Clinical
Systems Improvement (ICSI); 2008.
NGC summary available:
al+magnetic+stimulation%22 (accessed 09 Apr 2009)
See page 44
Full guideline available:
(accessed 09 Apr 2009)
Kristen Moulton, BA, Research Assistant
Charlene Argáez, MLIS, Information Specialist
Health Technology Inquiry Service
Transcranial Magnetic Stimulation Therapy for Patients with Refractory Depression 5
APPENDIX – FURTHER INFORMATION:
Randomized controlled trials
31. Turnier-Shea Y, Bruno R, Pridmore S. Daily and spaced treatment with transcranial
magnetic stimulation in major depression: a pilot study. Aust N Z J Psychiatry
2006;40(9):759-63. PubMed: PM16911750
Consensus statements and clinical Policy
32. Transcranial magnetic stimulation and cranial electric stimulation [clinical policy bulletin no.
0469]. In: AETNA [website]. Hartford (CT): AETNA; 2008.
http://www.aetna.com/cpb/medical/data/400_499/0469.html (accessed 09 Apr 2009)
33. Consensus statement on depression in adults: how to improve prevention, diagnosis and
treatment. Edmonton (AB): Institute of Health Economics; 2008.
http://www.ihe.ca/documents/Depression_Statement.pdf (accessed 09 Apr 2009)
Transcranial Magnetic Stimulation Therapy for Patients with Refractory Depression 6