Efficacy, tolerability, and cognitive effects of deep transcranial magnetic stimulation for late-life depression: a prospective randomized controlled trial
Open accessAbstract
Late-life depression (LLD) is a growing worldwide problem due to demographic changes, with limited treatment options due to high rates of pharmacotherapy adverse effects, accessibility of psychotherapy, and tolerability of electroconvulsive therapy. Novel neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), may overcome these limitations. The objective of this study is to determine the efficacy, tolerability, and cognitive effects of high-dose deep rTMS in LLD. In this study we randomized older adults between 60 and 85 years old with major depressive disorder (MDD) to sham or active deep rTMS (H1 coil, 6012 pulses, 18 Hz, 120% of resting motor threshold) delivered over the dorsolateral and ventrolateral prefrontal cortex 5 days per week over 4 weeks. Our primary outcome was remission of depression in an intention-to-treat analysis. We also assessed change in cognitive functioning with rTMS treatment and tolerability based on adverse effects. Fifty-two participants were randomized to active (n = 25) or sham H1 coil (n = 27). Remission rate was significantly higher with active than sham rTMS (40.0% vs 14.8%) with a number needed to treat of 4.0 (95% CI: 2.1-56.5). There was no change on any measure of executive function and no serious adverse events. Adverse effect profiles were similar between active and sham rTMS, except for reports of pain being significantly more common in the active condition (16.0% vs 0%). High-dose deep rTMS appears to be safe, well tolerated, and efficacious in the treatment of LLD.
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Deep TMS (dTMS) uses H-coils to extend stimulation to deeper targets and offers more favorable safety and tolerability profiles.
“Deep TMS (dTMS), utilizes H-coils to extend this stimulation to deeper targets, while also offering more favorable safety and tolerability profiles [6,100,101,102,103,104,105].”
From The Heart’s Electromagnetic Field in Emotions, Empathy and Human Connection: Biosensor-Derived Insights into Heart–Brain Axis Mechanisms and a Basis for Novel BioMagnetoTherapies (2026) · cites this paper as [104]
The Introduction says the H1 coil was designed to stimulate deeper brain volumes and is generally well tolerated. The Discussion reports good tolerability in this trial but says future trials are needed to compare it with conventional rTMS coils; the claimed more favorable comparative safety and tolerability profile is therefore not established. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn MDD and TRD, TMS targeting predominantly the left dorsolateral prefrontal cortex produces significant antidepressant effects with response and remission rates of 52.2% and 38.2%, respectively.
“MDD and TRD trials targeting predominantly the left dorsolateral prefrontal cortex, show significant antidepressant effects with response and remission rates of 52.2% and 38.2% accordingly [101,104,105,106,107].”
From The Heart’s Electromagnetic Field in Emotions, Empathy and Human Connection: Biosensor-Derived Insights into Heart–Brain Axis Mechanisms and a Basis for Novel BioMagnetoTherapies (2026) · cites this paper as [104]
The rTMS technique section says the H1 coil stimulated the dorsolateral and ventrolateral prefrontal cortex bilaterally, with greater intensity on the left. The Efficacy and Secondary outcome sections report significant antidepressant effects in older adults with MDD, but the active-group response and remission rates were 44.0% and 40.0% in the intention-to-treat analysis—not 52.2% and 38.2%. This trial does not establish those rates for MDD and TRD trials generally. Page numbers were not provided for these passages. (LLM, conf=0.90)
Experimental — accuracy not yet measuredRepetitive transcranial magnetic stimulation (rTMS) may have similar or potentially greater efficacy in older adults with MDD.
“It is also reported that repetitive transcra nial magnet ic stimulation (rTMS) may have similar (or po tentially great er with increased pulse dose) efficacy in older adults with MDD 113 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [113]
The remission rate of 35.4% in the bilateral TBS group is comparable to those in the authors' previous bilateral rTMS trial (33%) and deep rTMS trial (40%) and to aripiprazole augmentation in older adults with treatment-resistant depression.
“This remission rate is comparable with those seen in our previous bilateral rTMS trial (33%)7 and deep rTMS trial (40%)32 and comparable with the remission rate seen with aripiprazole augmentation in older adults with TRD.33”
A recent study of deep TMS (H1 coil) delivered over the dorsolateral and ventrolateral prefrontal cortex showed that deep TMS is safe in LLD and led to higher remission rate than sham rTMS (40.0 vs. 14.8%).
“A recent study of deep TMS (H1 coil) delivered over the dorsolateral and ventrolateral prefrontal cortex showed that deep TMS is safe in LLD and led to higher remission rate than sham rTMS (40.0 vs. 14.8%)182.”
From Mechanisms and treatment of late-life depression (2019) · cites this paper as [182]
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References 57 · Cited by 174
Research works printed but not linked: 3
- Mosimann UP, Marré SC, Werlen S, Schmitt W, Hess CW, Fisch HU, et al. Anti- depressant effects of repetitive transcranial magnetic stimulation in the elderly: correlation between effect size and coil-cortex distance. Arch Gen Psychiatry. 2002;59:560-1.
- George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, et al. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder. Arch Gen Psychiatry. 2010;67:507.
- First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, research version, patient edition. New York: Bio- metrics Research; 2002.
- Authors
- Kaster, T. S., Daskalakis, Z. J., Noda, Y., Knyahnytska, Y., Downar, J., Rajji, T. K., Levkovitz, Y., Zangen, A., Butters, M. A., Mulsant, B. H., & Blumberger, D. M.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Keio University (JP)
- University of Toronto (CA)
- Tel Aviv University (IL)
- Ben-Gurion University of the Negev (IL)
- University of Pittsburgh (US)
- Corresponding author
- Blumberger, Daniel M.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-06-18
- Volume
- 43
- Issue
- 11
- Pages
- 2231-2238
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6135812
- OpenAlex
- W2808186671
- Cited by
- 174
- References
- 57
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 29 · 2023: 25 · 2022: 23 · 2021: 18 · 2020: 23 · 2019: 14
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (ISO-115293)
- Canadian Institute for Health Research University-Industry Sponsored Operating Grant in conjunction with Brainsway Ltd.
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- geriatric depression, major depressive disorder, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, depression remission, cognitive effects, executive function, treatment tolerability, adverse effects, older adults, neuromodulation
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Cognition, Double-Blind Method, Female, Humans, Male, Middle Aged, Prospective Studies, Treatment Outcome, Transcranial Magnetic Stimulation, Executive Function, Depressive Disorder, Treatment-Resistant, Transcranial Direct Current Stimulation
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