| Transcranial magnetic stimulation | |
|---|---|
 Transcranial magnetic stimulation (schematic diagram) | |
| Specialty | Psychiatry,neurology |
| MeSH | D050781 |
Transcranial magnetic stimulation (TMS) is anoninvasiveneurostimulation technique in which a changingmagnetic field is used to induce anelectric current in a targeted area of thebrain throughelectromagnetic induction. A device called a stimulator generates electric pulses that are delivered to amagnetic coil placed against thescalp. The resulting magnetic field penetrates theskull and induces a secondary electric current in the underlying brain tissue, modulatingneural activity.[1][2]
Medical devices delivering repetitive transcranial magnetic stimulation (rTMS) have provided reasonably safe and effective treatments formajor depressive disorder (MDD),chronic pain, andobsessive-compulsive disorder (OCD).[3] They have shown evidence of effectiveness in the treatment of various neurological and psychiatric conditions—especiallydepression,neuropathic pain, andstroke recovery—and emerging advancements like intermittent theta burst stimulation (iTBS) and image-guided targeting may improve its efficacy and efficiency.[4][5]
Adverse effects of TMS appear rare and includefainting andseizure, which occur in roughly 0.1% of patients and are usually attributable to administration error.[6]
TMS does not require surgery or electrode implantation. Its use can be diagnostic and/or therapeutic. Effects vary based on frequency and intensity of the magnetic pulses as well as the length of treatment, which dictates the total number of pulses given.[8]
TheFood and Drug Administration (FDA) has cleared rTMS devices for use in the treatment of depression in the United States (US). TheNational Institute for Health and Care Excellence (NICE) has issued guidance in the United Kingdom (UK) for that use. Private clinics and someVeterans Affairs medical centers provide treatments for that use. TMS stimulates cortical tissue without the pain sensations produced intranscranial electrical stimulation.[9]
TMS can be used clinically to measure activity and function of specific brain circuits in humans, most commonly with single or paired magnetic pulses.[10] The most widely accepted use is in measuring the connection between the primary motor cortex of thecentral nervous system and theperipheral nervous system to evaluate damage related to past or progressive neurologic insult.[10][11] TMS has utility as a diagnostic instrument formyelopathy,amyotrophic lateral sclerosis, andmultiple sclerosis.[12]
The FDA has found that devices producing rTMS are reasonably safe and effective, as they have apparently produced improvements in a number of neurological and psychiatric disorders, including MDD (2008), headache pain (2013), and OCD (2018). Only minor adverse effects have usually accompanied these improvements.[3]
A group of European investigators has updated the therapeutic guidelines for rTMS, reviewing studies up to the end of 2018. They found the highest level of evidence, Level A (definite efficacy) for high-frequency rTMS of the primary motor cortex forneuropathic pain, high-frequency rTMS of the leftdorsolateral prefrontal cortex (DLPFC) fordepression, and low-frequency rTMS of the contralesional motor cortex for hand motor recovery afterstroke. Level B evidence (probable efficacy) was found in conditions such asfibromyalgia,Parkinson's disease, multiple sclerosis,post-traumatic stress disorder (PTSD), depression, and post-strokeaphasia, depending on the rTMS protocol used. No other conditions reached Level A or B evidence. These recommendations are based on differences in therapeutic outcomes between real and sham rTMS, replicated in multiple independent studies, although clinical relevance may still vary.[4]
A 2025 consensus review evaluated current clinical practices and recent advancements in rTMS for depression. The review concluded that rTMS is a safe and effective treatment modality, with a growing body of evidence supporting its use in treatment-resistant depression.[13] rTMS, particularly high-frequency stimulation of the left DLPFC, appears to have demonstrated reproducible acuteantidepressant effects in MDD, with growing evidence supporting its efficacy, durability, and potential superiority over medication in treatment-resistant cases. Traditional rTMS protocols have been established, while newer approaches—such as iTBS and individualized, image-guided targeting—have shown promise in reducing treatment time and potentially enhancing clinical outcomes.
Existing evidence suggests that rTMS, particularly targeting the DLPFC andsupplementary motor area, reduces OCD symptoms, while results for themedial prefrontal cortex andanterior cingulate cortex using deep transcranial magnetic stimulation are more variable; the overall heterogeneity of studies highlights the need for further research.[14] rTMS had a largeeffect size advantage over sham for depression (Hedges's g = 0.791) in a 2023meta-analysis.[15]
However, the effectiveness of rTMS and thequality of evidence behind it for treatment of depression have been questioned.[16] As withantidepressants and other interventions for depression, there is a largeplacebo response with shamcontrol groups in rTMS trials (Hedges's g = 0.8).[17]
The authors of a 2002Cochrane review of 14 evaluablerandomized controlled trials assessing the therapeutic efficacy and safety of TMS for depression concluded that there was no strong evidence for benefit from using TMS to treat depression. However, the small sample size did not exclude the possibility of benefit.[18]
A 2011 review found that only 13.5% of 96 randomized control studies of rTMS to the DLPFC had reportedblinding success and that, in those studies, people in real rTMS groups were significantly more likely to think that they had received real rTMS, compared with those in sham rTMS groups.[19] Depending on the research question asked and theexperimental design, matching the discomfort of rTMS to distinguish true effects from placebo can be an important and challenging issue.[20]
Two pivotal clinical trials led to the first FDA marketing authorizations for rTMS devicesindicated for use in treatment-resistant MDD in 2011 and 2013.[21][22] While the results of both trials reportedly hadstatistical significance at 6 weeks post-treatment, interventions outperformed sham bymeans of only 2 to 3 points on the 60-pointMontgomery–Åsberg Depression Rating Scale (MADRS).[23] In the primary outcome measure for the second such trial, there were only 18remitters (9.5% of theintention-to-treat population): 14.1% in the active treatment arm and 5.1% in the sham treatment arm. Theodds ratio for the remitters was 4.2; 95% confidence interval, 1.32-13.24;p = .02. Thenumber needed to treat (the average number of patients who need to be treated to prevent one additional bad outcome) was 12.[24]
TMS is generally advertised as a safe alternative to medications such asSSRI's. The greatest immediate risk from TMS isfainting, though this is uncommon.Seizures have been reported, but are rare.[6][25]
Risks are higher for therapeutic rTMS than for single or paired diagnostic TMS.[26] Adverse effects generally increase with higher frequency stimulation.[6] In a randomized controlled trial investigating the antidepressant effects of daily rTMS to the left DLPFC using an active electrical sham stimulation system, the pain associated with active, but not sham, TMS decreased rapidly over time.[27]
During the procedure, a magnetic coil is positioned at the head of the person receiving the treatment using anatomicallandmarks on the skull, in particular theinion andnasion.[7] The coil is then connected to a pulse generator, or stimulator, that delivers electric current to the coil.[2]
TMS useselectromagnetic induction to generate an electric current across thescalp andskull.[28][29] A plastic-enclosed coil of wire is held next to the skull and when activated, produces a varyingmagnetic field orientedorthogonally to the plane of the coil. The changing magnetic field then induces an electric current in the brain that activates nearby nerve cells in a manner similar to a current applied superficially at the cortical surface.[30]
The magnetic field is about the same strength asmagnetic resonance imaging (MRI), and the pulse generally reaches no more than 5 centimeters into the brain unless using a modified coil and technique for deeper stimulation.[29]
Transcranial magnetic stimulation is achieved by quickly discharging current from a largecapacitor into a coil to produce pulsedmagnetic fields between 2 and 3teslas in strength.[31] Directing the magnetic field pulse at a targeted area in the brain causes a localized electrical current which can then eitherdepolarize orhyperpolarize neurons at that site. The induced electric field inside the brain tissue causes a change in transmembrane potentials resulting in depolarization or hyperpolarization of neurons, causing them to be more or less excitable, respectively.[31]
TMS usually stimulates to a depth from 2 to 4 cm below the surface, depending on the coil and intensity used. Consequently, only superficial brain areas can be affected.[32] Deep TMS can reach up to 6 cm into the brain to stimulate deeper layers of themotor cortex, such as that which controls leg motion. The path of this current can be difficult to model because the brain is irregularly shaped with variable internal density and water content, leading to a nonuniform magnetic field strength andconduction throughout its tissues.[33]
The effects of TMS can be divided based on frequency, duration and intensity (amplitude) of stimulation:[34]
Most devices use a coil shaped like a figure-eight to deliver a shallow magnetic field that affects more superficial neurons in the brain.[39] Differences in magnetic coil design are considered when comparing results, with important elements including the type of material,geometry and specific characteristics of the associated magnetic pulse.
The core material may be either a magnetically inert substrate ('air core'), or a solid,ferromagnetically active material ('solid core'). Solid cores result in more efficient transfer of electrical energy to a magnetic field and reduce energy loss to heat, and so can be operated with the higher volume of therapy protocols without interruption due tooverheating. Varying the geometric shape of the coil itself can cause variations infocality, shape, and depth of penetration. Differences in coil material and its power supply also affect magnetic pulse width and duration.[40]
A number of different types of coils exist, each of which produce different magnetic fields. The round coil is the original used in TMS. Later, the figure-eight (butterfly) coil was developed to provide a more focal pattern of activation in the brain, and the four-leaf coil for focal stimulation of peripheral nerves. The double-cone coil conforms more to the shape of the head.[41] The Hesed (H-core), circular crown and double cone coils allow more widespread activation and a deeper magnetic penetration. They are supposed to impact deeper areas in the motor cortex andcerebellum controlling the legs andpelvic floor, for example, though the increased depth comes at the cost of a less focused magnetic pulse.[6]
TMS is oftentimes combined withelectroencephalography (EEG) to assess functional connectivity.[42] Low-profile electrodes have been developed for concurrent TMS–EEG in order to reduce mechanical coupling and maintain stable contact during stimulation; one example is the ultra-flat TMS–EEG electrode g.Ladybird, developed by g.tec medical engineering GmbH, an Austria-based neurotechnology company.[43]
For Parkinson's disease, early results suggest that low frequency stimulation may have an effect on medication associateddyskinesia, and that high frequency stimulation improves motor function.[44]
Thecerebellar cortex as a possible target of TMS has been investigated in combination with EMG, and a reduction in the average amplitude ofmotor-evoked-potentials in small hand muscles has been observed when comparing paired-pulse TMS with a 6-8 ms interstimulus interval between cerebellar TMS and TMS to the primary motor cortex with single-pulse TMS to the primary motor cortex - a phenomenon termed cerebellum brain inhibition (CBI).[45][46] Recent investigations have built upon this phenomenon to investigate the feasibility of combining EEG with cerebellar TMS to find signatures of the cerebellum-to-cerebrum functional connectivity in high temporal resultion.[47] By applying control conditions accounting for multisensory input and concomitant occipital cortex stimulation, and confirming effective cerebellar TMS by assessing CBI beforehand and modelling the induced electric field, EEG signatures of cerebellar TMS were proposed - as they may be utilized as therapeuticbiomarkers to test pharmacotherapy efficacy inspinocerebellar ataxia in the future.[48][49][50] However, these EEG signatures are still openly debated in the field of Brain Stimulation due to their inconsistency - likely, differing stimulation targets due to the lack ofneuronavigation in these studies explain these discrepancies in results.[51]
Luigi Galvani (1737–1798) undertook research on the effects of electricity on the body in the late-eighteenth century and laid the foundations for the field ofelectrophysiology.[52] In the 1830s,Michael Faraday (1791–1867) discovered that anelectrical current had a correspondingmagnetic field, and that changing one could induce its counterpart.[53]
Work to directly stimulate the human brain with electricity started in the late 1800s, and by the 1930s the Italian physiciansCerletti andBini had developedelectroconvulsive therapy (ECT).[52] ECT became widely used to treatmental illness, and ultimately overused, as it began to be seen as apanacea. This led to a backlash in the 1970s.[52]
In 1980, Merton and Morton successfully used transcranial electrical stimulation (TES) to stimulate the motor cortex. However, this process was very uncomfortable, and subsequently Anthony T. Barker began to search for an alternative to TES.[54] He began exploring the use of magnetic fields to alter electrical signaling within the brain, and the first stable TMS devices were developed in 1985.[52][53][55] They were originally intended as diagnostic and research devices, with evaluation of their therapeutic potential being a later development.[52][53] The FDA first cleared a TMS device for marketing in December 2009.[56]
As of January 2026, the FDA had authorized under two regulatory pathways the marketing of more than 50 TMS devices for various indications of use within the United States.[57] These pathways are (1) thepremarket notification (PMN), also known as a 510(k) submission, and (2) thede novo classification request.[58]
The FDAclears medical devices for marketing under a PMN if it finds that the intended use and technological characteristics of a new device are "substantially equivalent" to a legally marketed device (termed a "predicate device"). The FDA also clears medical devices for marketing under a PMN if it finds that (1) a new device has the same intended use as the predicate and has different technological characteristics, (2) the information submitted to the FDA does not raise new types of questions of safety and effectiveness, and (3) the information demonstrates that the new device has a comparable risk-to-benefit profile to a legally marketed device.[58] The agency grantsde novo classification requests if it finds that the data and information provided demonstrate that general controls or general and special controls are adequate to provide a reasonable assurance of safety and effectiveness, and the probable benefits of the device outweigh the probable risks.[58] Among the devices authorized for marketing under these two pathways are:
In December 2009, in response to a PMN, theFinnish company Nexstim OY obtained FDA clearance for the Nexstim eXimia Navigated Brain Stimulation System for the non-invasive mapping of the primary motor cortex of the brain to its cortical gyrus for the assessment of the primary motor cortex for pre-procedural planning.[56] In May 2012, in response to a subsequent PMN, the company obtained such clearance for the Nexstim Navigational Brain Stimulation System 4 and the Nexstim NBS System 4 with NEXSPEECH® for the localization and assessment of cortical areas of speech function for pre-procedural planning purposes.[59]
In July 2011, in response to a petition by the US company,Neuronetics, Inc., the FDA classified under itsde novo classification pathway the NeuroStar TMS System as aClass II (moderate risk) medical device for the treatment of MDD in patients who have failed to receive benefit from one antidepressant trial.[21]
In January 2013, in response to a PMN by theIsraeli company, Brainsway, Ltd., the FDA cleared the Brainsway Deep TMS System for the treatment of depressive episodes in adult patients suffering from MDD who failed to achieve satisfactory improvement from previous antidepressant medication treatment in the current episode.[22]
In May 2015, in response to a PMN by the UK company, The Magstim Company Ltd., the FDA cleared the Rapid2 Therapy System for the treatment of MDD in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.[60]
In September 2021, in response to a PMN by The Magstim Company Ltd., the FDA cleared the Horizon 3.0 TMS Therapy System for the treatment of MDD in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.[61]
In March 2023, in response to a PMN by The Magstim Company Ltd., the FDA cleared the Horizon 3.0 TMS Therapy System for the treatment of depressive episodes and for decreasing anxiety symptoms for those who may exhibit comorbid anxiety symptoms in adult patients suffering from MDD and who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.[62]
In October 2023, in response to a PMN by The Magstim Company Ltd., the FDA cleared the Horizon 3.0 TMS Therapy System for the treatment of MDD in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode, as well as an adjunct for the treatment of adult patients suffering from OCD.[63]
In March 2013, in response to a request by the US company eNeura Therapuetics LLC, the FDA classified under itsde novo classification pathway as a Class II medical device the eNeura Therapeutics® CerenaTM Transcranial Magnetic Stimulator for the acute treatment of pain associated with migraine headache with aura[64]
In September 2017, the FDA classified the Brainsway Deep Transcranial Magnetic Stimulation System as an adjunct for the treatment of adult patients suffering from OCD as a Class II medical device under itsde novo classification pathway in response to a request from Brainsway Ltd.[65] In August 2018, the FDA permitted the marketing of the device for the treatment of OCD in response to a subsequentde novo classification request from the company.[66]
In August 2020, the FDA cleared the MagVenture TMS Therapy system for the treatment of OCD in response to a PMN by theDanish company Tonica Elektronik A/S.[67]
In May 2022, the FDA cleared the NeuroStar Advanced Therapy for the adjunctive treatment of OCD in response to a PMN by Neuronetics, Inc.[68]
In October 2023, in response to a PMN by The Magstim Company Ltd., the FDA cleared the Horizon 3.0 TMS Therapy System for the treatment of MDD in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode, as well as an adjunct for the treatment of adult patients suffering from OCD.[69]
In August 2018, in response to a request by Brainsway Ltd., the FDA classified under itsde novo classification pathway the generic type of device transcranial magnetic stimulation system for neurological and psychiatric disorders and conditions as a Class II medical device that is identified as a prescription, non-implantable device that uses brief duration, rapidly alternating, or pulsed, magnetic fields to induce neural activity in the cerebral cortex.[70]
In August 2020, the FDA cleared the Brainsway Deep TMS System for use as an aid in short term smoking cessation in adults in response to a PMN by Brainsway Ltd.[71]
In 1993, the US House of Representatives' Subcommittee on Oversight and Investigations of itsCommittee on Energy and Commerce issued a report entitled "Less Than The Sum Of Its Parts". The report identified a number of continued organizational and structural weaknesses that had made theFDA Center for Devices and Radiological Health unable to either adequately protect the public from unsafe devices or to approve useful and safe devices in a reasonable period of time.[72] A 2010 review of the FDA's regulatory procedures subsequently contended that, among other things, the agency's reviews of medical devices had a lower approval standard than their drug counterparts, excessively relied upon a fast-track process, and failed to conduct Congressionally-mandated device classifications.[73]
In theEuropean Economic Area, various versions of deep TMS H-coils haveCE marking forAlzheimer's disease,[74]autism,[74]bipolar disorder,[75]epilepsy,[76]chronic pain,[75]MDD,[75]Parkinson's disease,[77]PTSD,[75][78]schizophrenia (negative symptoms)[75]and to aid smoking cessation.[74]One review found tentative benefit for cognitive enhancement in healthy people.[79]
The United Kingdom's NICE issues guidance to theNational Health Service (NHS) in England, Wales, Scotland, and Northern Ireland. NICE guidance does not address whether the NHS should fund a procedure. Local NHS bodies (primary care trusts andhospital trusts) make decisions about funding after considering the clinical effectiveness of the procedure and whether the procedure represents value for money for the NHS.[80]
NICE evaluated TMS for severe depression in 2007, finding that TMS was safe, but with insufficient evidence for its efficacy.[81] Guidance was updated and replaced in 2015, concluding that evidence for short‑term efficacy of rTMS for depression was adequate, although the clinical response is variable, and ruling that rTMS for depression may be used with arrangements for clinical governance and audit.[82]
In January 2014, NICE reported the results of an evaluation of TMS for treating and preventing migraine (IPG 477). NICE found that short-term TMS is safe but there is insufficient evidence to evaluate safety for long-term and frequent uses. It found that evidence on the efficacy of TMS for the treatment of migraine is limited in quantity, that evidence for the prevention of migraine is limited in both quality and quantity.[83]
As of 2025[update], use of rTMS in the UK was reported to have remained limited due to the cost of equipment and establishing treatment centres. Camilla Nord, head of the Mental Health Neuroscience Lab at theUniversity of Cambridge said, "The NHS has unfortunately been far behind the US and Canada on rTMS, which is at least as effective as antidepressants, if not more".[84]
 | This section needs to beupdated. Please help update this article to reflect recent events or newly available information. Last update: February 2014(September 2025) |
In 2013, several commercial health insurance plans in the United States, includingAnthem,Health Net,Kaiser Permanente, andBlue Cross Blue Shield ofNebraska and ofRhode Island, covered TMS for the treatment of depression for the first time.[85] In contrast,UnitedHealthcare issued a medical policy for TMS in 2013 that stated there is insufficient evidence that the procedure is beneficial for health outcomes in patients with depression. UnitedHealthcare noted that methodological concerns raised about the scientific evidence studying TMS for depression include small sample size, lack of a validated sham comparison in randomized controlled studies, and variable uses of outcome measures.[86] Other commercial insurance plans whose 2013 medical coverage policies stated that the role of TMS in the treatment of depression and other disorders had not been clearly established or remained investigational includedAetna,Cigna andRegence.[87]
Policies for Medicare coverage vary among local jurisdictions within the Medicare system,[88] and Medicare coverage for TMS has varied among jurisdictions and with time. For example:
There are serious concerns about stimulating brain tissue using non-invasive magnetic field methods such as uncertainty in the dose and localisation of the stimulation effect.[93]
{{cite journal}}: CS1 maint: multiple names: authors list (link)The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.
There have been more than 20 randomized, controlled trials investigating the efficacy of rTMS in the treatment of major depression. The most common deficiency noted is the relatively small sample sizes of these studies. The sample size varied from 6 to 70. Most of the studies used sample sizes less than 20.
We included 29 systematic reviews and re-analysed 15 meta-analyses. ..... Authors of all included meta-analyses interpreted findings to suggest TMS is safe and effective for MDD despite lack of comprehensive investigation of heterogeneity. Our re-analysis revealed the direction and magnitude of treatment effects vary widely across different settings. We also found high risk of bias in the majority of included systematic reviews and presence of small-study effects in some meta-analyses. Because of these reasons, we argue TMS for MDD may not be as effective and potentially less tolerated in some populations than current evidence suggests.
Placebo response was large (g=0.8, 95% CI=0.65-0.95, p<0.01) regardless of the modality of intervention.
Mimicking the cutaneous sensation experienced during rTMS has been a challenging aspect of developing an optimal sham condition (see Ruohonen, et al., 2000;Lisanby, et al., 2001; Sommer et al., 2006a; Rossi et al., 2007b; Arana et al., 2008). The cutaneous sensation is caused when rTMS stimulates scalp muscles producing a twitch in the scalp or upper face that can be uncomfortable for some, painful for others.
On May 23, 2007, Neuronetics, Inc., submitted a petition requesting classification, under section 513(f)(2) of the FD&C Act, of the NeuroStar® TMS System for the treatment of major depressive disorder in patients who have failed to receive benefit from one antidepressant trial. The manufacturer recommended that the device be classified into class II
Lisanby, however, states that the published trial showed 'TMS to be safe and efficacious' (Lisanby et al, 2009). This is misleading. In the trial (O'Reardon et al, 2007), the difference between treatment arms was both statistically and clinically non-significant (p=0.057, 1.7 points on the 60-point Montgomery Asberg Depression Rating Scale) for the primary outcome (change in Montgomery Asberg Depression Rating Scale at 4 weeks). This finding only became statistically significant (p=0.038) after the post hoc exclusion of six patients even though they had met a priori inclusion criteria, an obviously inappropriate statistical maneuver.
When manufacturers submit a 510(k), they must compare their device to a legally-marketed predicate device that does not require review through the premarket approval (PMA) process. Substantial equivalence does not mean the device under review and predicate devices must be identical. A device is determined to be substantially equivalent to a legally-marketed predicate device if it: • has the same intended use as the predicate AND has the same technological characteristics as the predicate; OR • has the same intended use as the predicate AND has different technological characteristics and the information submitted to FDA: - does not raise new types of questions of safety and effectiveness; AND demonstrates that the device has a comparable risk-to-benefit profile to a legally marketed device.
This article incorporates text from this source, which is in thepublic domain.A series of subcommittee hearings and investigations have documented a number of instances in which the FDA approved devices that proved unsafe in use. In every case that the subcommittee examined, personnel within the FDA were aware of problems with the device at the time of approval. The subcommittee also found systemic defects within the FDA: excessive delays in the review and approval process of device applications; low morale and productivity among staff within the office of Device Evaluation (ODE); inadequate use of science; poor or nonexistent communications between the device industry and the Agency; and organizational laws that have made the whole of the Center less than the sum of its parts. Thus, CDRH has problems at both ends of the approval spectrum: it has approved devices that have safety and effectiveness concerns, yet it also has been slow to approve potentially very beneficial devices.