Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that uses magnetic pulses generated by a coil placed on the scalp to induce focal electrical currents in the cerebral cortex. In major depression, the most extensively studied target is the dorsolateral prefrontal cortex, which is part of frontolimbic networks involved in regulation of mood, motivation and cognitive control.
Unlike electroconvulsive therapy, rTMS is normally performed while the patient is awake, does not require anesthesia and is not intended to induce a seizure. It is an established treatment for major depressive episodes, particularly when response to antidepressants has been insufficient or medication tolerability is problematic. Efficacy nevertheless depends on the protocol, targeting accuracy, the dose actually delivered and the patient’s clinical characteristics.
The term rTMS encompasses different techniques: conventional high or low frequency stimulation, bilateral protocols, intermittent theta burst stimulation (iTBS), deep TMS with dedicated coils and accelerated protocols studied in specialist centers. These modalities should not be considered interchangeable without taking account of the evidence and specific authorization for each device and protocol.
A brief, intense current passes through the coil and generates a magnetic field that penetrates superficial tissues without requiring intracranial electrodes. The changing field induces a current in brain tissue according to the principles of electromagnetic induction. The immediate effect depends on coil geometry, orientation, distance from the scalp, intensity and individual anatomical properties; the clinical effect of a repeated course instead derives from changes in network excitability and plasticity that persist beyond the individual session.
The simplification that “high frequency excites and low frequency inhibits” is useful for teaching but does not capture the full physiology. In the motor cortex, some patterns produce relatively predictable effects on excitability, whereas in the prefrontal cortex the response is modulated by network state, medications, sleep, anatomical variability and individual differences. The antidepressant effect is interpreted as modulation of distributed circuits rather than correction of a single “underactive” area.
The classic target is the left DLPFC for high frequency excitatory protocols or iTBS, whereas the right DLPFC is used in low frequency protocols and bilateral strategies. Localization can be performed using scalp based measurements, standardized systems or MRI guided neuronavigation. More recent approaches seek to select prefrontal sites based on connectivity with cingulate or limbic structures, but personalization based on individual connectivity is not yet a universal routine requirement.
rTMS is considered primarily in patients with major depression who have not achieved an adequate response to one or more treatments or who have contraindications or poor medication tolerability. The likelihood of response tends to decrease with extreme levels of treatment resistance, very long episode duration and substantial comorbidity, but these factors are not automatic exclusions. Psychotic or catatonic features and the need for a rapid lifesaving response may instead make ECT more appropriate.
Before treatment, the diagnosis and mood phase should be confirmed, previous treatments documented, and suicide risk, seizure history, neurological disorders, head trauma, substances, medications that alter seizure threshold, and the presence of metal or electronic devices near the head assessed. Cochlear implants, brain stimulators and other devices may pose a significant issue with the magnetic field and require specific verification by the manufacturer and treatment center.
Protocol selection depends on the evidence, session duration, device availability and the patient’s history. Left sided iTBS demonstrated noninferiority to high frequency rTMS in a large pragmatic study and allows much shorter sessions. Deep TMS uses coils with different geometry and broader, deeper field distributions; results obtained with one coil or regulatory indication cannot automatically be transferred to other configurations.
Motor threshold is estimated by eliciting a motor response through stimulation of the motor cortex and serves as an individual reference for intensity. The prescription includes intensity relative to threshold, frequency, number of pulses, pattern, intervals and number of sessions. Even when two protocols have the same name, differences in these parameters can produce a different neurophysiological dose.
A traditional acute course extends over several weeks with repeated sessions on weekdays; iTBS reduces the duration of each session without eliminating the need for a treatment course. Accelerated protocols, which concentrate multiple sessions in the same day with defined intervals, are a rapidly evolving area. Some individualized accelerated protocols have produced notable results in controlled studies, but they should not be confused with standard rTMS or reproduced outside validated procedures and devices.
Response is monitored through clinical assessment and standardized scales. Incomplete improvement may lead to extension of the course or modification of the protocol, whereas absence of benefit requires review of diagnosis, target, dose, session adherence and the overall treatment strategy. There is no single number of sessions that guarantees response or universally defines treatment failure.
Randomized sham controlled studies and meta analyses show that active rTMS produces higher response and remission rates than sham in patients with major depression, with particularly strong evidence for high frequency left prefrontal stimulation and modern protocols such as iTBS. The absolute effect depends on the population: studies involving less treatment resistance tend to show better outcomes than cohorts with numerous treatment failures.
Comparison with other treatments requires caution. rTMS is less invasive than ECT and has a favorable cognitive profile, but ECT has stronger clinical evidence in psychotic or extremely severe depression. Compared with tDCS, rTMS has a more established evidence base and clinical implementation in many jurisdictions, but it is more expensive and requires dedicated equipment and staff.
After an acute response, relapse can occur. Continuation and maintenance strategies include pharmacotherapy, psychotherapy and additional rTMS sessions that are scheduled or restarted at early signs of relapse. Studies support the possibility of maintaining benefit in some patients, but frequency, duration and criteria for reintroduction are not yet uniform; scheduling should therefore be individualized.
The most frequent adverse events are scalp discomfort or pain, headache, facial muscle contractions and local sensations during the pulses. They tend to decrease with habituation or technical adjustments. Coil noise requires adequate hearing protection for the patient and operators.
The most important acute complication is a seizure, but risk is very low when protocols remain within safety limits. Risk increases with predisposing factors such as previous epilepsy, brain lesions, sleep deprivation, substances or medications that lower seizure threshold. A history of epilepsy does not necessarily constitute an absolute prohibition, but it requires specialist assessment and an explicit benefit to risk evaluation.
Hypomanic or manic switches have been described in patients with bipolar disorder or vulnerability to activation; energy, sleep, impulsivity and mood polarity should therefore be monitored. rTMS does not typically produce the memory deficits associated with ECT, and cognition remains stable or improves in parallel with depression in many studies, but this does not eliminate the need to observe any unexpected neurological or cognitive symptoms.
Treatment is not recommended or requires particular caution in the presence of ferromagnetic material or field sensitive devices in the cranial region. The mere presence of metallic prostheses far from the coil cannot be assessed generically: compatibility depends on location, material and device. Screening, emergency procedures and operator training are as much components of safety as compliance with stimulation parameters.
rTMS occupies an intermediate position between pharmacological or psychotherapeutic treatments and more intensive procedures. It is particularly useful when a nonsystemic treatment with minimal pharmacokinetic interference and no anesthesia is desired. It can be combined with antidepressants and psychotherapy; there is no reason to automatically discontinue an effective and tolerated treatment unless specific clinical needs dictate otherwise.
Optimal selection requires defining the objective: remission of the episode, functional recovery, reduction of future treatment resistance and prevention of relapse. In a patient with severe but stable depression, without psychosis or catatonia and with several medication failures, rTMS may be a rational choice. If the patient instead has malnutrition, catatonic stupor or immediate suicide risk, priority may shift toward interventions with greater speed and certainty of action.
Future directions include connectivity based targeting, individualized dosimetry, response biomarkers and accelerated protocols. These innovations are promising, but technological optimization does not replace clinical assessment: diagnostic quality, appropriate management of comorbidity and continuity of care remain key determinants of outcome.
The timing of rTMS also depends on the history of previous responses and patient preferences. Previous benefit from rTMS may support another course if relapse occurs, whereas nonresponse should prompt review of dose, target, protocol and degree of treatment resistance before concluding that the entire class is ineffective. Accelerated protocols and connectivity based targeting strategies are expanding treatment possibilities, but they should not be considered equivalent to standard protocols without specific data. Within the overall treatment pathway, rTMS therefore occupies a position between pharmacotherapy or psychotherapy and more invasive treatments, with a favorable balance between efficacy and tolerability in selected patients.
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