Neurostimulation & neurofeedback
Transcranial Magnetic Stimulation (TMS) for Depression
Graded on: response and remission in treatment-resistant major depression on blinded clinician-rated scales (HAM-D, MADRS).
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How this letter has changedLatest: October 2026 · Corrected.
grade_basis scoped the A to left prefrontal high-frequency or theta-burst stimulation while two supporting trials used H1-coil deep TMS at 18 Hz (Levkovitz et al., 2015; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 25655160; Kaster et al., 2018; PMID 29946106), one in late-life depression; the ref, grade_basis and replication The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away. block now say so, and disclose the coil maker's sponsorship of the Levkovitz trial and in-kind equipment for the Kaster trial beside the Neuronetics funding already stated for O'Reardon. The record said a pooled analysis found no effect on suicidal ideation; Mehta et al. (2022; PMID 35044731) found a non-significant reduction in randomized trials, now stated. Added: Eren et al. (2026; PMID 41997374), 30 sham-controlled comparisons with larger effects in single-blind trials; Zhang et al. (2026; PMID 42383744), 141 trials with only 3 at low risk of bias; Orbo et al. (JAMA Netw Open, 2026; PMID 42418203), an independent sham-controlled theta-burst trial positive on blinded MADRS at day 10 and not sustained. The O'Reardon baseline-adjustment caveat is confirmed by that trial's abstract and stands. A unchanged. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 25655160 PMID 29946106 PMID 35044731 PMID 41997374 PMID 42383744 PMID 42418203
New device record, and the first letter set under the Grade A rule as revised in September 2026, which now counts a validated outcome scale scored by a clinician blinded to treatment. On the Hamilton and Montgomery-Asberg scales, sham-controlled trials in treatment-resistant depression replicate across more than 100 randomized trials (Mutz et al., BMJ 2019; PMID 30917990), including an NIH trial with an active sham A fake version of a procedure or device used as the comparison, so participants cannot tell which one they received. (George et al., Arch Gen Psychiatry 2010; PMID 20439832). The record keeps what the letter does not cover: no trial shows fewer suicide attempts or hospitalizations, about one extra remission per 8 to 12 people treated, an effect that fades after the course ends, and a Veterans Affairs trial with no difference from sham (Yesavage et al., JAMA Psychiatry 2018; PMID 29955803).PMID 30917990 PMID 20439832 PMID 29955803
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TMS uses magnetic pulses aimed at the front of the brain to treat depression. It was studied in adults whose depression did not get better with at least one antidepressant. In more than 100 trials, trained raters who did not know who got real treatment found more people improved than with fake treatment. The gain is modest, about one extra person well again for every 8 to 12 treated, and it fades after treatment ends. No trial shows fewer suicide attempts or hospital stays. Seizure is the most serious risk, though it is rare.
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
See the full evidence record →Graded on Response and remission in treatment-resistant major depression on blinded clinician-rated scales (HAM-D, MADRS).
Why this gradeThe reasoning, and what the grade does not cover.
Grade A under the rule as revised in September 2026, which counts a validated outcome scale scored by a clinician blinded to treatment alongside hard outcomes and instrument-measured function. The Hamilton and Montgomery-Asberg scales are scored by trained raters who do not know which treatment the patient received; they are not questionnaires the patient fills in. On those scales the effect has been replicated across more than 100 randomized trials in many countries, with consistent odds ratios near 3 for response, a European guideline rating of Level A, and an active sham in the NIH trial that held the blind. Two of the supporting trials used H1-coil deep TMS at 18 Hz (Levkovitz et al., 2015; PMID 25655160; Kaster et al., 2018; PMID 29946106), a different coil and frequency from the figure-8 trials; the letter rests on the figure-8 and theta-burst trials and their pooled analyses, with the deep TMS trials as supporting context, and the deep TMS pivotal trial was sponsored by the coil's maker.
WHAT THIS GRADE DOES NOT COVERno randomized trial shows fewer suicide attempts, hospitalizations or relapses, and a pooled analysis found a non-significant reduction in suicidal ideation in randomized trials (Mehta et al., 2022; PMID 35044731). Trial quality is uneven: in a 2026 network meta-analysis A study that pools the numbers from several trials into one combined estimate. of 141 trials only 3 were at low risk of bias and most comparisons were rated low or very low confidence (Zhang et al., 2026; PMID 42383744), and effects are larger in single-blind than double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. trials (Eren et al., 2026; PMID 41997374). The absolute gain is modest, about one extra remission for every 8 to 12 people treated, and it fades in the months after a course ends. A 164-patient Veterans Affairs trial found no difference from sham. Accelerated protocols (SAINT and similar) rest on far fewer trials and are not what this letter describes. It covers adults with major depression that did not respond to at least one antidepressant, treated with high-frequency or theta-burst stimulation of the left prefrontal cortex.
Shared endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.: Depression remission or response on the Hamilton or Montgomery-Asberg scale, scored by blinded raters, active versus sham TMS
- Multisite US trial (O'Reardon): Greater improvement than sham on blinded MADRS and HAM-D ratings, 301 patients. PMID 17573044 · Funding: manufacturer-funded (Neuronetics)
- OPT-TMS, NIMH-funded multisite (George): Remission 14.1 percent versus 5.1 percent with sham, raters masked, 190 patients. PMID 20439832 · Funding: government (NIMH)
- Multicenter deep TMS trial (Levkovitz): Remission 32.6 percent versus 14.6 percent with sham on blinded HDRS-21, 212 patients, H1 coil at 18 Hz. PMID 25655160 · Funding: manufacturer-funded (Brainsway)
- Toronto (Kaster), Canadian Institutes of Health Research: Remission 40.0 percent versus 14.8 percent with sham, 52 older adults, H1 coil at 18 Hz. PMID 29946106 · Funding: government (CIHR), with in-kind equipment from Brainsway
What the replication does not cover: Effect sizes How large a difference the treatment made, as distinct from whether the difference could be detected at all. are modest and remission rates low in medication-resistant patients. The two deep TMS trials use a different coil and frequency from the figure-8 trials; the Levkovitz trial was maker-sponsored and the Kaster trial received the maker's equipment. Effects are larger in single-blind than double-blind trials, and only 3 of 141 trials in the 2026 network meta-analysis were at low risk of bias.
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Seizure is the most serious known risk. It is rare, and the deep TMS pivotal trial reported one, linked to a protocol violation. People with metal implants in or near the head, cochlear implants, implanted stimulators, or a history of seizures need screening before treatment. Headache and scalp discomfort are common. Treatment is prescribed and supervised by a psychiatrist under the device's FDA labeling.
The evidence, in full15 papers, each linked to its PubMed record.
George et al. (Arch Gen Psychiatry, 2010; PMID 20439832): NIH-funded trial with an active sham that reproduced scalp sensation; remission 14.1% versus 5.1%, number needed to treat 12, masking held. O'Reardon et al. (Biol Psychiatry, 2007; PMID 17573044): 301 patients, sham-controlled; remission about double with active treatment, with the primary MADRS comparison significant only after a baseline adjustment. Levkovitz et al. (World Psychiatry, 2015; PMID 25655160): 212 patients, deep TMS with the H1 coil at 18 Hz, a different coil and frequency from the figure-8 trials; remission 32.6% versus 14.6%; sponsored by the coil's maker (Brainsway), whose developers are among the authors. Kaster et al. (Neuropsychopharmacology, 2018; PMID 29946106): 52 older adults aged 60 to 85 with late-life depression, H1-coil deep TMS; remission 40.0% versus 14.8%; funded by the Canadian Institutes of Health Research, with in-kind equipment support from the coil's maker declared. Berlim et al. (Psychol Med, 2014; PMID 23507264): meta-analysis of 29 trials, 1,371 patients; remission 18.6% versus 5%, number needed to treat 8. Brunoni et al. (JAMA Psychiatry, 2017; PMID 28030740) and Mutz et al. (BMJ, 2019; PMID 30917990): network meta-analyses of 81 and 113 trials; high-frequency left prefrontal stimulation response odds ratio about 3. Lefaucheur et al. (Clin Neurophysiol, 2020; PMID 31901449): European guideline, Level A. Berlim et al. (Int J Neuropsychopharmacol, 2013; PMID 23399312): blinding held in the trials that tested it. Kept in the record: Yesavage et al. (JAMA Psychiatry, 2018; PMID 29955803), 164 veterans, remission 40.7% versus 37.4%, no difference; Kedzior et al. (Depress Anxiety, 2015; PMID 25683231), effect smaller 8 to 16 weeks after treatment ends; Mehta et al. (J Clin Psychiatry, 2022; PMID 35044731), a non-significant reduction in suicidal ideation in randomized trials (g 0.16, confidence interval The range the true effect probably falls in. A wide interval means the estimate is uncertain. crossing zero) and a significant one only in uncontrolled studies. Pooled analyses through 2026: Eren et al. (J Affect Disord, 2026; PMID 41997374), 30 sham-controlled comparisons and 1,850 patients, response odds ratio 4.78 and remission 3.55, with larger effects in single-blind than double-blind trials; Zhang et al. (J Evid Based Med, 2026; PMID 42383744), network meta-analysis of 141 trials and 10,587 patients, high-frequency left stimulation response odds ratio 3.34, with only 3 trials at low risk of bias and most comparisons rated low or very low confidence. Orbo et al. (JAMA Netw Open, 2026; PMID 42418203): 73 patients in North Norway, 10 once-daily sessions of theta-burst stimulation against a validated sham coil; better than sham on blinded MADRS at day 10 (3.6 points), not on the self-rated BDI-II, and not sustained at 4 weeks.
A clinician-rated depression scale (HAM-D or MADRS) at baseline, weekly during the course, and at 1, 3 and 6 months after it ends, because the trials found the effect fades without maintenance.
Evidence notes: randomized trial, meta-analysis
Endpoint graded: Response and remission in treatment-resistant major depression on blinded clinician-rated scales (HAM-D, MADRS) (clinician_rated)
Last reviewed: September 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
As studiedDose, form, population and duration for every use.
Accelerated multi-session-per-day protocols are marketed as faster versions of the same treatment; they rest on far fewer randomized trials and this grade does not describe them.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Primary evidence15 papers, each linked to its PubMed record.
George et al. (Arch Gen Psychiatry, 2010; PMID 20439832): NIH-funded trial with an active sham that reproduced scalp sensation; remission 14.1% versus 5.1%, number needed to treat 12, masking held. O'Reardon et al. (Biol Psychiatry, 2007; PMID 17573044): 301 patients, sham-controlled; remission about double with active treatment, with the primary MADRS comparison significant only after a baseline adjustment. Levkovitz et al. (World Psychiatry, 2015; PMID 25655160): 212 patients, deep TMS with the H1 coil at 18 Hz, a different coil and frequency from the figure-8 trials; remission 32.6% versus 14.6%; sponsored by the coil's maker (Brainsway), whose developers are among the authors. Kaster et al. (Neuropsychopharmacology, 2018; PMID 29946106): 52 older adults aged 60 to 85 with late-life depression, H1-coil deep TMS; remission 40.0% versus 14.8%; funded by the Canadian Institutes of Health Research, with in-kind equipment support from the coil's maker declared. Berlim et al. (Psychol Med, 2014; PMID 23507264): meta-analysis of 29 trials, 1,371 patients; remission 18.6% versus 5%, number needed to treat 8. Brunoni et al. (JAMA Psychiatry, 2017; PMID 28030740) and Mutz et al. (BMJ, 2019; PMID 30917990): network meta-analyses of 81 and 113 trials; high-frequency left prefrontal stimulation response odds ratio about 3. Lefaucheur et al. (Clin Neurophysiol, 2020; PMID 31901449): European guideline, Level A. Berlim et al. (Int J Neuropsychopharmacol, 2013; PMID 23399312): blinding held in the trials that tested it. Kept in the record: Yesavage et al. (JAMA Psychiatry, 2018; PMID 29955803), 164 veterans, remission 40.7% versus 37.4%, no difference; Kedzior et al. (Depress Anxiety, 2015; PMID 25683231), effect smaller 8 to 16 weeks after treatment ends; Mehta et al. (J Clin Psychiatry, 2022; PMID 35044731), a non-significant reduction in suicidal ideation in randomized trials (g 0.16, confidence interval crossing zero) and a significant one only in uncontrolled studies. Pooled analyses through 2026: Eren et al. (J Affect Disord, 2026; PMID 41997374), 30 sham-controlled comparisons and 1,850 patients, response odds ratio 4.78 and remission 3.55, with larger effects in single-blind than double-blind trials; Zhang et al. (J Evid Based Med, 2026; PMID 42383744), network meta-analysis of 141 trials and 10,587 patients, high-frequency left stimulation response odds ratio 3.34, with only 3 trials at low risk of bias and most comparisons rated low or very low confidence. Orbo et al. (JAMA Netw Open, 2026; PMID 42418203): 73 patients in North Norway, 10 once-daily sessions of theta-burst stimulation against a validated sham coil; better than sham on blinded MADRS at day 10 (3.6 points), not on the self-rated BDI-II, and not sustained at 4 weeks.
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