Name: Conventional Repetitive Transcranial Magnetic Stimulation for Depression: A Step-by-Step Protocol (Video) | JoVE Journal
Uploaded: 2025-11-21T13:00:00.000+00:00
Duration: 10 min 54 s
Description: Learn conventional repetitive transcranial magnetic stimulation for treatment-resistant depression using precise scalp measurements and patient-centered techniques. This protocol enhances safety, comfort, and reproducibility in clinical settings.

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GC is supported by a 2023 NARSAD Young Investigator Grant from the Brain &#38; Behavior Research Foundation. AJO-M is supported by a Starting Grant from the European Research Council (grant agreement no. 950357), and by the PsyPal project (grant agreement no. 875358), both funded by the European Union&#39;s Horizon 2020 Research and Innovation Programme. GC and AJO-M are supported by a Proof-of-Concept Grant from the European Research Council (grant agreement no. 101158262). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of any of the funding agencies.

AJO-M is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and was national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33); has received payment, honoraria, or support for attending meetings and participating in advisory boards from MSD, Neurolite AG, Janssen Pharmaceuticals, Angelini Pharma, and the European Monitoring Centre for Drugs and Drug Addiction; has received consultancy fees from Bioprojet Pharma and NaturalX Health Ventures (all outside the submitted work); is Vice President of the Portuguese Society for Psychiatry and Mental Health; is head of the Psychiatry Working Group for the National Board of Medical Examination at the Portuguese Medical Association and Portuguese Ministry of Health; is President of the Ethics Committee for the Public Institute for Addictive Behaviors and Dependence; and is President of the Scientific Council of the Portuguese Obsessive Compulsive Disorder Foundation. The remaining authors declare that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written. None of these agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript.

The implementation of a standardized TMS protocol in clinical settings ensures consistency in treatment delivery, optimizes patient outcomes, and enhances the reliability of therapeutic interventions for depression17. The protocol outlined in this study provides a structured framework for clinicians and technicians, addressing key procedural elements such as patient preparation, motor hotspot determination, and treatment site localization. By maintaining adherence to these steps, clinicians can reduce variability in treatment application14,37,38, thereby potentially increasing the likelihood of achieving optimal clinical outcomes. Furthermore, integrating psychometric assessments at predefined intervals allows for systematic tracking of patient response, ensuring that treatment adjustments can be made based also on empirical data. In contrast to existing guidelines23, this protocol specifies structured ramping strategies to optimize patient comfort during initial sessions and incorporates predefined psychometric assessment timelines to guide systematic, data-driven treatment adjustments.
Decision-making about the use of TMS to treat an episode of depression should be a collaborative decision between the patient and the prescribing clinician. In most circumstances, the clinician is a psychiatrist, already responsible for patient care, or to whom the patient was referred for assessment of the potential use of TMS. Indications with regulatory approval include TRD, with and without co-morbid anxiety, but also OCD and substance use disorders, with recent clearance of a protocol&#160;for&#160;smoking cessation11. Protocols cleared by regulatory agencies for depression include high-frequency L-DLPFC stimulation11,39. Off-label uses may be considered based on clinical evidence and expert guidelines. Additionally, promising data also support potential future use for other psychiatric syndromes, namely negative symptoms of schizophrenia and post-traumatic stress disorder, still lacking regulatory approval11,12.
While the focus of this article is on a protocol for conventional rTMS, other protocols are also available. The selection of a specific TMS protocol should be guided by the attending physician, considering both patient and clinician preferences, the specific TMS device available, and the level of experience of the clinical staff. An accelerated TMS protocol (Stanford Neuromodulation Treatment) has been cleared by the FDA for treatment-resistant depression11,16, but is not widely accessible in most TMS centers, despite being a very promising treatment strategy, namely regarding speed of onset36,37. Other protocols, such as low-frequency rTMS targeting the R-DLPFC&#160;or bilateral stimulation involving both the L- and R-DLPFC, have demonstrated clinical efficacy6,12. However, these approaches currently hold lower recommendation levels12 and have not yet received regulatory clearance or approval11. Low-frequency rTMS of the R-DLPFC, which may be required when high-frequency stimulation is not tolerated and/or the L-DLPFC is not accessible, is conducted with procedures for determining MH, rMT, and TS as described above, but adapted for the right hemisphere and left hand.
Ethical and regulatory issues should govern TMS use in clinical practice17,18. A fundamental requirement is obtaining informed consent, which must be free and prior to treatment, based on providing all relevant information about procedures, potential risks, and discomforts in an understandable way17,18. Informed consent should clearly discuss the possibility of the occurrence of side effects, particularly a seizure, and clinicians must ensure patients understand the information provided17,18. Full disclosure of the treatment plan, including whether off-label protocols are used, is critical in the informed consent process17,18. Safety is another critical consideration17,18. While generally safe and well-tolerated, the most serious acute adverse effect is the occurrence of a seizure, which is extremely rare when treatment is delivered within recommended parameters11,17,18. Certain conditions and medications can increase the risk of seizures, such as a personal history of epilepsy, brain lesions, administration of drugs lowering seizure threshold, sleep deprivation, and alcoholism18. Other adverse effects, mostly mild and self-limited, can include scalp pain, headache, muscle twitching, dizziness, nausea, anxiety, insomnia, hypomania, and tinnitus11,17,18,39. Absolute contraindications include the presence of metallic hardware in close contact with the coil, such as cochlear implants or implanted pulse generators, due to the risk of inducing device malfunction18. Other conditions, like pregnancy or severe heart disease, involve increased or uncertain risk18.
Patient comfort and adherence40,41,42 play crucial roles in treatment success43. The protocol includes specific measures to improve tolerability, such as initial familiarization with TMS sensations, the use of earplugs to enhance auditory safety, and the implementation of ramping strategies to gradually increase stimulation intensity. These adaptations are particularly valuable for individuals who experience discomfort during early sessions, potentially improving patient retention and overall treatment effectiveness43. The inclusion of structured post-session evaluations also enables the early detection and management of side effects, reinforcing patient safety and engagement throughout the treatment course43.
In addition to TMS equipment with local regulatory approval or clearance (e.g., CE mark in the EU, FDA in the US), sites where rTMS is delivered should be equipped with appropriate life-support equipment, and access to emergency medical facilities is also advised in medical environments where outpatient TMS treatments are delivered18. TMS clinics must have an explicit plan to address syncope and seizures, and every member of the TMS team must be familiar with it18. For suspected syncope, lying the patient down in a supine position with legs elevated is appropriate18. In case of seizures, efforts should focus on preventing complications like aspiration, turning the patient on one side (left lateral decubitus position is desirable) once movement ceases18. TMS-induced seizures are typically brief and self-limited, delayed recovery of consciousness beyond 30 s warrants further medical evaluation18. While life-support equipment should be available in TMS clinical centers18&#160;for outpatient clinical settings applying standard protocols, the consensus of the Clinical TMS Society is that intravenous access, cardiac defibrillators, suction, and oxygen are not necessary17.
Appropriate training for personnel is a crucial step in setting up a TMS clinic19. The required credentials and training depend on the site and the local regulatory requirements, as well as the type and purpose of the TMS application17,18,19. At our center, this includes completion of a certified TMS training program and supervised performance of TMS. Trainees should demonstrate proficiency in MH localization and rMT determination, accurate coil positioning, and adherence to safety procedures, before independent operation. Periodic re-assessment and refresher training are also recommended to maintain standardization. Particularly when rTMS is used as treatment for a medical condition, a licensed physician, serving as the medically responsible clinician, supervises application of treatments, which can be carried out by a trained medical assistant17,18,19. TMS technicians, especially those without medical training, should have basic knowledge of brain physiology, TMS mechanisms, potential risks, and physiological changes induced by treatment17,18,19. It is also recommended that TMS technicians have cardiopulmonary or basic life support training17,18. Additionally, personnel skilled in the management of syncope and seizure should be present in TMS clinics17,18. Finally, for routine clinical treatment sessions, a physician should be accessible in case of an emergency17,18.
Another critical component of effective TMS administration is the precise determination of the stimulation site17. Here, we highlight the importance of using structured non-neuronavigated approaches such as the 5 cm rule and the Beam F3 method to identify the L-DLPFC as the primary target for depression treatment44,45. While non-neuronavigated methods are practical, they nevertheless have limitations such as inherent inter-individual anatomical variation, with implications for precision, accuracy, and reproducibility45,46,47,48. On the other hand, while neuronavigation offers the highest accuracy49, limited availability in clinical settings may limit access if other methods are not used17. Moreover, neuronavigation did not offer a consistent clinical advantage when compared to non-neuronavigated methods50. The step-by-step protocol presented here provides detailed guidance on the latter approaches, ensuring that even without neuronavigation, treatment sites can be determined consistently and reliably27. Future research should explore how progress in imaging technology and real-time neuronavigation could further enhance the precision and efficacy of TMS interventions.
The structured assessment sessions incorporated into the protocol provide an evidence-based approach to monitor treatment efficacy and patient response. Regular psychometric assessment using standardized instruments such as the BDI-II and MADRS allows clinicians to track improvements and determine whether modifications to the treatment plan are necessary24,27. Moreover, periodic reassessments of the rMT&#160;ensure that stimulation parameters remain optimal, accounting for any physiological changes that may occur over the course of treatment27,51. While this is expected to contribute significantly to the safety of rTMS, recent evidence indicates that neither motor threshold and its stability, nor treatment intensity, reliably predict clinical outcomes27,52. Finally, baseline assessments, such as the YMRS, may be used to identify patients at risk of mania, hypomania, or mixed states50. In such cases, treatment adjustments may include closer clinical monitoring and coordination with the prescribing physician, medication adjustments (e.g., optimizing mood stabilizers) to mitigate the risk of mood switching, and consideration of the need to postpone rTMS treatment50. This systematic approach underscores the importance of objective, data-driven decision-making in TMS therapy.
Depending on the resources and protocols of each TMS center, as well as patient preference, treatment may transition to a maintenance phase TMS protocol if this is considered of clinical interest14. This decision is typically based on clinical response to TMS and risk of relapse, and follows a pre-defined schedule (e.g., weekly, or biweekly sessions) that can be adjusted according to ongoing psychiatric evaluation. While no standardized protocol exists for transitioning to maintenance, a gradual reduction in session frequency is commonly employed (e.g., three sessions per week, then two sessions per week, and finally weekly) until the target maintenance schedule (e.g., biweekly) is reached14,30. Symptom prompted maintenance protocols have also been described, where short cycles of rescue TMS session are applied when symptoms relapse14,30. Currently, there is no evidence to support a given type of maintenance strategy over another14,30.
Even with a structured protocol, challenges may occur during rTMS administration. Difficulty eliciting or locating the motor hotspot can often be addressed by verifying coil orientation and contact, exploring adjacent scalp positions, increasing intensity in small steps, and ensuring that the patient is relaxed17,18,36. If a patient does not tolerate stimulation, strategies include ramping intensity over initial sessions, slightly adjusting coil placement, or using over-the-counter analgesics17,18,36. In case of session interruptions&#160;due to equipment issues, patient discomfort, or unforeseen events, the session should be paused, the problem resolved, and stimulation resumed only once correct coil positioning and patient readiness are re-confirmed. Coil instability can be minimized with proper head and neck support, consistent cap alignment, and coil-holding devices17,18. Variability in motor threshold measurements should prompt reassessment and review of technique and equipment if changes are abrupt17,18,24,36. Auditory discomfort is best prevented with well-fitted, regularly replaced earplugs17,18. Applying these measures improves comfort, accuracy, and treatment consistency.
While our goal is to offer practical guidance for the clinical use of TMS in depression, several limitations merit note. First, we rely on non-neuronavigated scalp targeting (5 cm rule, Beam F3). These methods are accessible and standardized but depend on individual anatomy and can reduce placement precision. Neuronavigation may improve coil-placement accuracy, but it is not universally available and has not shown a consistent clinical advantage in treatment outcomes. Second, while rMT-based dosing is essential for safety and standardization, it does not reliably predict antidepressant efficacy. Nevertheless, to date, no alternative dosing approach has shown sufficiently consistent results to replace rMT as the dosing anchor. Finally, we present maintenance treatment as optional because schedules vary across centers and no single strategy has proven superior. Future work should define more specific, evidence-based maintenance schedules.
In conclusion, the protocol outlined in this study provides a comprehensive, step-by-step framework for application of rTMS in the treatment of depression, balancing standardization with individualized care. Variability in clinical outcomes is addressed through the use of consistent targeting methods, clear stimulation parameter definitions, and structured procedural steps, while still allowing flexibility for patient-specific adjustments. In resource-rich settings, integration of neuronavigation and targeting based on functional imaging may further enhance precision and reproducibility. Future studies should focus on optimizing stimulation parameters, refining targeting strategies, and evaluating the long-term efficacy of structured TMS protocols, including the role of maintenance sessions and personalized adjustments in sustaining therapeutic benefits beyond the acute phase.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation technique based on the principle of electromagnetic induction1. If an electric current passes through a TMS coil, it generates an electromagnetic field perpendicular to the current&#39;s direction1. When this field interacts with conductive material, such as neural tissue, it induces electrical activity1. This enables targeted modulation of neuronal activity in discrete regions of the cerebral cortex, opening new avenues for both neuroscientific research and clinical applications2. The evolution of TMS technology led to the development of repetitive TMS (rTMS), involving the delivery of repeated electromagnetic pulses to a target cortical region at a predetermined frequency3. High-frequency rTMS (&#8805; 5 Hz) typically facilitates cortical excitability, whereas low-frequency rTMS (&#8804; 1 Hz) suppresses it3. More complex protocols for rTMS, such as intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS), also allow for modulation of brain activity and have been integrated into clinical practice3.
The therapeutic potential of rTMS for psychiatric disorders was first explored in the 1990s, with studies demonstrating its effects in patients with medication-resistant depression4,5. Since then, numerous clinical trials and meta-analyses have established rTMS as a safe and effective treatment for neuropsychiatric disorders6. In 2008, the U.S. Food and Drug Administration (FDA) cleared high-frequency rTMS for episodes of treatment-resistant depression (TRD)7,8,9,10, marking the first official neuropsychiatric application of the technique11. Subsequent regulatory decisions followed, including clearance of iTBS for TRD in 2018, following evidence of equivalent efficacy to the conventional TMS protocol, and of rTMS for obsessive-compulsive disorder (OCD) in 2019, as well as designation of rTMS as a breakthrough therapy for bipolar depression11. The European regulatory framework, through the Conformit&#233; Europ&#233;enne (CE) Mark, has similarly certified multiple TMS devices and protocols for clinical use11.
Evidence-based recommendations from expert consensus&#160;and clinical guidelines have reinforced the therapeutic role of rTMS in depression12. Robust clinical data support its efficacy in TRD, with response rates ranging from 39.5% to 70% and remission rates between 16.6% and 76.9%13. Importantly, the antidepressant effects of TMS have been shown to persist, with 53% of responders maintaining improvements at six months and 46% at one-year post-treatment14. The left dorsolateral prefrontal cortex (L-DLPFC) is the cleared target for depression treatment, though alternative protocols involving right DLPFC stimulation or bilateral approaches have also been explored15. Conventional treatments offer daily stimulation sessions across several weeks, while more recent accelerated protocols have been developed with multiple sessions per day for a shorter period16. In this work, adding to existing guidelines17, we aim to&#160;provide a step-by-step guide for application of conventional rTMS to treat a major depressive episode, incorporating elements such as structured ramping strategies, predefined psychometric assessment timelines, and detailed comfort and safety measures, within a clinical setting that ensures consistency, effective treatment delivery, and adherence to regulatory clearances or recommendations11. Hence, we aim to provide guidance for clinical application of TMS to treat depression, towards mitigating variability in application of treatments, while improving tolerability, consistency, and real-world implementation.

<table><tbody><tr><td>BA9 BA8 BA43&lt;br/&gt; Location System</td><td>Will Beam &amp;amp; Jeff Borckardt</td><td>Web Interface&lt;br/&gt; Developed 6/7/2010</td><td>https://clinicalresearcher.org/F3/</td></tr><tr><td>Computer Desktop/Laptop</td><td>Irrelavant</td><td>Not applicable&amp;nbsp;</td><td>Required to access BeamF3 website</td></tr><tr><td>Confortable Chair</td><td>Irrelavant</td><td>Not applicable&amp;nbsp;</td><td>For the patient to seat while all TMS procedures are performed</td></tr><tr><td>Cool-B65 Coil</td><td>Magventure</td><td>9016E0491</td><td>TMS coil</td></tr><tr><td>Microsoft Excel&amp;nbsp;</td><td>Microsoft</td><td>Office 365 Personal</td><td>Useful to store TMS patients clinical data</td></tr><tr><td>Paper</td><td>Irrelevant</td><td>Not applicable&amp;nbsp;</td><td>Required to print the psychometric instruments and the score sheets</td></tr><tr><td>Pen</td><td>Irrelevant</td><td>Not applicable&amp;nbsp;</td><td>Required to complete the psychometric instruments&amp;nbsp;</td></tr><tr><td>Printer</td><td>Irrelevant</td><td>Not applicable&amp;nbsp;</td><td>Required to print the psychometric instruments and the score sheets</td></tr><tr><td>Transcranial Magnetic Stimulation (TMS) MagPro X100</td><td>Magventure</td><td>9016D0041</td><td>TMS operaring system</td></tr></tbody></table>

conventional repetitive transcranial magnetic stimulation for depression: a step-by-step protocol

Conventional Repetitive Transcranial Magnetic Stimulation for Depression: A Step-by-Step Protocol

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive approach for brain stimulation, with proven effectiveness and efficacy to treat Major Depressive Disorder (MDD), particularly for episodes that do not respond to antidepressant medication. A structured patient-centered Transcranial Magnetic Stimulation (TMS) protocol, focused on precision, comfort, and safety, should be provided in TMS clinics treating MDD. The procedure begins with the patient seated comfortably in a reclining chair, equipped with head and foot support. A pillow is placed around the patient&#39;s neck to ensure head stability and comfort throughout the session. A lycra cap is placed on the patient&#39;s head, and the treatment area is&#160;marked on the cap to ensure the correct placement of the electromagnetic coil. Two main strategies, relying on the head landmarks for each individual patient, have been widely used to identify the treatment area: the 5 cm rule and the Beam F3 method. To initiate the treatment, the coil is positioned on the treatment target to deliver a series of electromagnetic pulses. Patients hear a clicking sound and feel a light tapping sensation on the scalp. For acoustic protection, earplugs are provided before the session begins. The stimulation itself typically causes no discomfort, and patients can resume their normal daily activities after the session. However, driving is discouraged immediately after treatment sessions. The rTMS protocol to treat MDD consists of 20 to 30 daily sessions over four to six weeks, monitored by regular consultations with a psychiatrist, to track progress and adjust if needed. Maintenance sessions may follow to sustain clinical benefits. This step-by-step protocol ensures comfort, consistency, and effective treatment delivery for patients undergoing rTMS therapy.

The efficacy of transcranial magnetic stimulation for the treatment of major depression episodes has been consistently confirmed in multiple meta-analyses, with response rates ranging from 40% to 70% and remission rates from 17% to 77%13. Consequently, its clinical and research applications have been expanding33. However, significant variability in treatment outcomes persists13, possibly due to differences in protocols across TMS centers12. Here, we provide a structured, step-by-step guide that promotes consistency across centers, towards enhancing clinical efficacy and patients' quality of life. Additionally, standardizing protocols facilitates more robust clinical data collection, contributing to research in real-world settings24,27,34.
As an example, our TMS center routinely applies this standardized protocol and has contributed to a real-world evidence study evaluating the efficacy of TMS for depression24. This study, which analyzed data from over 500 patients across several centers in multiple countries, compared treatment outcomes between older and younger adults24. At the Champalimaud Foundation, the study was approved by the Champalimaud Ethics Committee, and informed consent was obtained from all participants. Between May 2019 and April 2021, 35 patients treated at our site met eligibility criteria for inclusion. For this study, in addition to eligibility for treatment with rTMS for TRD, participants were excluded if age or motor threshold data were missing, the treatment device was changed mid-course, fewer than 10 sessions were completed, or the average interval between sessions was ≥ 2.5 days. The mean age was 48.6 ± 16 years, and 51.4% were female. The most common indication for referral was unipolar depression (80%), with 20% of patients diagnosed with bipolar depression. The majority of patients (88.6%) received iTBS over the L-DLPFC. In cases where the left-sided protocol was not tolerated, a right-sided (R-DLPFC) low-frequency protocol used (11.4%). The rMT was assessed weekly, consistent with procedures from our previous research27. The mean baseline rMT was 59.4 ± 14.0%, and the end-of-treatment rMT was 58.1 ± 16.8%. Most patients (80%) completed the full six-week acute treatment, with 8.6%, 2.9%, 5.7%, and 2.9% completing only five, four, three, and two weeks, respectively. No dropouts were attributed to protocol-related issues (e.g., coil discomfort, inability to reach target rMT), and non-completion resulted from dropout due to unspecified reasons. The clinical outcomes are illustrated in Figure 1. Mean MADRS reduction was 9.13 (± 9.82 SD), which was significantly different from zero (one-sample t-test, p &lt; 0.001). Response and remission rates were not substantially different from previously reported evidence supporting the efficacy of TMS in the treatment of depressive disorders13. Regarding technician variability, we used a two-way mixed-effects model to calculate the intraclass correlation coefficient (ICC) for absolute agreement in rMT assessment between the first two weekly rMT measurements. Analyses were performed separately for measurements taken by the same technician (intra-rater) and by different technicians (inter-rater). Both ICC values indicated excellent reliability (ICCIntra = 0.92, 95% CI 0.75-0.98, F[11,11] = 23.79; p &lt; 0.001; ICCInter = 0.88, 95% CI 0.75-0.95; F[22,22] = 6.4; p &lt; 0.001).
Regarding the results of the overall sample, while both age groups demonstrated similar overall antidepressant responses, older adults exhibited a delayed response compared to their younger counterparts24. These findings suggest that extending the duration of TMS treatment may be necessary to achieve comparable therapeutic outcomes in older patients and aligns with previous research confirming the effectiveness of TMS in older populations, while highlighting the potential for age-specific adaptations in treatment protocols35.
Integrating these findings into clinical practice requires careful consideration, as they directly support key aspects of the TMS protocol outlined in this work. Specifically, they emphasize the need for regular and extended monitoring of treatment progress, as well as the critical role of effectively managing patient concerns and expectations regarding the varying effects of TMS36. Moreover, they highlight the importance of developing individualized treatment plans that incorporate comprehensive and routine assessments of multiple determinants, including socio-demographic factors (e.g., age), clinical variables (e.g., concomitant medication regimens), and treatment-related parameters (e.g., motor hotspot, motor threshold, and treatment site determination)17. These factors play a crucial role in optimizing both clinical efficacy and treatment tolerance6.
<img alt="MADRS score change, treatment effect, line graph; patient response percentages, bar chart analysis." class="xfigimg" src="/files/ftp_upload/68891/68891fig1.jpg" data-altupdatedat="1783396841000" data-alt="Figure 1"> 
Figure 1: Antidepressant effect after 6 weeks of treatment. (A) Severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Mean MADRS reduction was 9.13 (± 9.82 SD), which was statistically significantly different from zero (one-sample t-test, p &lt; 0.001). Error bars correspond to a 95% Confidence Interval. (B) A partial responder was defined as a patient who experiences at least a 25% reduction in the severity of depression, while a responder was considered if 50% or greater reduction of symptom severity was observed24. Finally, remission was defined as a total score of MADRS ≤ 1016,26. Clinical outcomes were similar to what has been previously reported13. Error bars correspond to a 95% Confidence Interval.<a href="https://www.jove.com/files/ftp_upload/68891/68891fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

This protocol presents a guide for the precise and patient-centered application of repetitive transcranial magnetic stimulation for treatment-resistant major depression. Details are provided on procedures for accurate coil localization, adjustable stimulus dosing, rigorous safety measures, and strategies that maximize comfort, reproducibility, and long-term clinical effectiveness across acute and maintenance sessions.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive approach for brain stimulation, with proven effectiveness and efficacy to treat ...

We describe conventional methods for therapeutic use of RTMS for treatment-resistant depression through precise and patient-centered protocol enhancing safety, comfort, and reproducibility. Recent advances include accelerated RTMS protocols, neuronavigation-based targeting, and personalized targeting using individual level functional brain connectivity, which are thought to improve treatment outcomes. While exciting developments are occurring for the use of RTMS to treat depression, establishing even the more conventional protocols can be challenging in some settings.To begin, place a lycra cap on the patient to mark areas of interest on the scalp. Confirm that the cap is aligned with the patient's eyebrows and the upper part of the ears to ensure consistent reference points for future sessions. Provide earplugs to the patient to minimize discomfort caused by stimulating sounds.Wear your own earplugs before beginning the transcranial magnetic stimulation procedure. Record all preparatory steps and safety measures in the patient's clinical chart. To determine the motor hotspot, identify the stimulation hotspot for the primary motor cortex of the hand region in the left hemisphere, using a measuring tape measure and mark the mid sagittal line extending from the nasion, which is the top of the nose bridge, to the inion, which is the prominent bump at the back of the skull.Now mark the intertragus line by placing one end of the measuring tape at one tragus, which is the point just in front of the ear, and stretching it across to the opposite tragus. Identify the intersection of the midsagittal and intertragus lines as the cranial vertex. Use this point as the reference from which additional measurements will be taken to locate the motor cortex hotspot.Next, draw a triangle by extending a line five centimeters to the left along the intertragus line, and another five centimeters anteriorly along the midsagittal line. Both starting from the cranial vertex. Connect the free ends of these two lines diagonally to form a triangle.The starting reference point for locating the hand motor hotspot is positioned 2.5 centimeters along this diagonal line measured from the leftmost vertex of the triangle. Then mark four additional points located 0.5 centimeters, anterior, posterior, lateral, and medial from the reference point. To allow detailed exploration during hotspot identification, use these five points as the designated positions where the anterior edge of the transcranial magnetic stimulation coil will be placed during the motor hotspot detection procedure.Before initiating the search for the motor hotspot, instruct the patient to rest their arms and hands on the armrests of the chair or on their lap, ensuring that both are visible and relaxed. Place the handle of the figure of eight transcranial magnetic stimulation coil on the patient's head at a 45 degree angle relative to the sagittal midline with the handle directed posteriorly and to the left. Apply transcranial magnetic stimulation pulses while maintaining the coil in the previously described position.To help the patient become accustomed to the procedure, deliver the initial pulses at a lower intensity, approximately 20%to 30%of the maximum output, while assessing the patient's sensory experience. Confirm the visible muscle contraction in the contralateral hand muscles. If no motor response is observed at the initial intensities across the marked reference points, increase the stimulation intensity in 5%increments until a motor response defined as a visible contraction of the right hand is obtained.Once a motor response is detected, test the remaining marked points to identify the location that produces the strongest contraction. Mark additional reference points as necessary at new positions spaced approximately one centimeter apart to refine the search. Identify the motor hotspot as the point that produces the largest and most consistent muscle contraction.After locating the optimal stimulation site, trace a concave line along the anterior edge of the coil and mark the midpoint of this line to indicate the precise hotspot location. Now, confirm the identified motor hotspot at regular intervals. If refinement is required during a session or treatment cycle, mark the new hotspot on the patient's cap and record the reason for adjustment in the clinical chart.To determine the resting motor threshold, begin assessment after allowing the patient a short accommodation period. Deliver transcranial magnetic stimulation pulses at percent of the devices maximum output, and confirm that visible muscle contractions of the contralateral hand occur in at least five out of 10 pulses. If visible contractions in at least five of 10 pulses are not achieved, increase the stimulation intensity in 2%increments until this response criterion is met.Once the criterion is achieved, decrease the intensity by 1%to identify the minimum level that still elicits a motor response in at least five of 10 pulses. Record the resting motor threshold in the patient's clinical chart for use in upcoming treatment sessions. If reassessment of the resting motor threshold is required, record the new resting motor threshold value along with the reason for reassessment.After identifying the motor hotspot and determining the resting motor threshold, proceed to locate the treatment site. This procedure focuses on non-neuronavigated approaches based on scalp measurements as these methods are commonly used in clinical practice. Using the five centimeter rule method, extend a parasagittal line anteriorly from the midpoint of the concave line drawn after determining the motor hotspot.Mark the stimulation point for the left dorsolateral prefrontal cortex at a position between five and six centimeters, most commonly 5.5 centimeters along this line. Then position the coil on the treatment site. Alternatively, use the Beam-F3 method to locate the F3 position from the 10-20 electroencephalogram system on the scalp as an alternative landmark For the left dorsolateral prefrontal cortex.Input the specific head measurements of the patient into a freely available software that provides instructions for marking F3 according to head size. Using a tape, measure the nasion-inion distance from the top of the nose bridge to the bump at the back of the skull. Second, measure the intertragus distance from one ear's tragus to the other.Third, measure the head circumference by passing the tape over the eon at eyebrow level. Input the three measurements into the software to generate two output distances. The first output, Point X, provides the distance to the left of the midline along the head circumference, and the second gives the distance from the vertex along a line intersecting Point X.Use these two distances to mark Point Y on the patient's scalp as the left dorsolateral prefrontal cortex treatment site.Finally, confirm the treatment site at regular intervals. If refinement is necessary, mark the updated treatment site on the patient's cap and document the reason for adjustment in the clinical chart, whether by protocol or due to other factors. After determining the treatment site, initiate the TMS protocol.A total of 35 treated patients were included in this study of real world evidence. Mean MADRS total score decreased significantly after six weeks of treatment compared to baseline. The mean reduction in MADRS was 9.13 points, demonstrating a statistically significant antidepressant effect after the treatment period.Following treatment, 56.7%of patients achieved partial response. 46.7%met the criteria for response, and 43.3%reached remission. We provided a standardized RTMS protocol that may improve treatment consistency, reliability, and comfort, supporting effective depression therapy across clinical settings.Conventional RTMS has paved the way for research focusing on optimizing stimulation parameters, refining strategies for cortical targeting, and evaluating the long-term effectiveness of RTMS for depression.

conventional-repetitive-transcranial-magnetic-stimulation-for

Research

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Source: Dunlop, K., et al. MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder. J. Vis. Exp. (2015)This video demonstrates the procedure for MRI-guided repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex (dmPFC) to treat depression.

MRI-Guided Repetitive Transcranial Magnetic Stimulation to the Dorsomedial Prefrontal Cortex

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

This article presents a clinical protocol for repetitive transcranial magnetic stimulation (rTMS) with individualized symptom provocation in obsessive-compulsive disorder (OCD), following parameters from protocols cleared by the FDA.

Protocol for Repetitive Transcranial Magnetic Stimulation with Symptom Provocation to Treat Obsessive-compulsive Disorder

This protocol describes the workflow of robotically delivered fMRI-guided personalized transcranial magnetic stimulation therapy for treatment-resistant depression. Clinical implementation using this protocol is feasible, and open-label results support the real-world effectiveness of this approach.

Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system.  Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Measuring gyrification (cortical folding) at any age represents a window into early brain development. Hence, we previously developed an algorithm to measure local gyrification at thousands of points over the hemisphere1. In this paper, we detail the computation of this local gyrification index.

How to Measure Cortical Folding from MR Images: a Step-by-Step Tutorial to Compute Local Gyrification Index

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia.  After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Learn conventional repetitive transcranial magnetic stimulation for treatment-resistant depression using precise scalp measurements and patient-centered techniques. This protocol enhances safety, comfort, and reproducibility in clinical settings.

Conventional Repetitive Transcranial Magnetic Stimulation for Depression: A Step-by-Step Protocol

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