Repetitive transcranial magnetic stimulation (rTMS) is widely recognized as a groundbreaking and non-invasive neuromodulation technique, primarily employed in the treatment of major depressive disorder (MDD). Praised for its favorable safety profile and minimal adverse effects, rTMS has revolutionized psychiatric therapeutics by targeting specific cortical brain regions to modulate neural activity. However, despite extensive studies endorsing its efficacy and safety, emerging clinical evidence suggests that this intervention may, under certain conditions, precipitate unexpected cardiovascular complications. In a pioneering case report recently published in BMC Psychiatry, researchers have documented the first known instance of severe bradycardia triggered by rTMS in a patient simultaneously battling MDD and premature ventricular contractions (PVCs). This unexpected cardiac response calls for a cautious reevaluation of rTMS’s cardiovascular implications, particularly in vulnerable patient populations.
The patient in question is a 46-year-old Chinese woman with a longstanding history of MDD spanning seven years and PVCs persisting for six years. Prior to rTMS initiation, her clinical regimen included paroxetine, a selective serotonin reuptake inhibitor; tandospirone citrate, an anxiolytic and serotonin receptor partial agonist; and metoprolol, a beta-adrenergic blocker commonly used for arrhythmia management. Remarkably, despite long-term beta-blocker therapy, the patient’s resting heart rate remained within normal limits, with no observed bradycardia or episodes of syncope, underscoring the chronic stability of her cardiovascular status before neuromodulation treatment commenced.
Upon introducing rTMS to her therapeutic plan, the patient exhibited a profound autonomic disturbance characterized by severe bradycardia—markedly reduced heart rate significantly below baseline. Intriguingly, this adverse effect emerged despite the withdrawal of metoprolol following initial bradycardic episodes, suggesting that the neuromodulatory intervention itself rather than pharmacologic agents precipitated the cardiac anomaly. The bradycardia persisted for several days, refractory to conventional management focused on the underlying arrhythmia, only to resolve one day after discontinuation of rTMS sessions. Notably, the symptomatic bradycardia reemerged upon recommencement of rTMS, further strengthening the association between magnetic stimulation and cardiac rhythm alterations.
The pathophysiological basis underpinning this phenomenon remains speculative but is likely rooted in rTMS’s influence on the autonomic nervous system (ANS), which governs vital cardiovascular parameters including heart rate modulation. The frequent targeting of the dorsolateral prefrontal cortex during rTMS—which is intricately connected to central autonomic networks—may inadvertently disrupt the delicate balance between sympathetic and parasympathetic output. Such perturbation could enhance vagal tone or suppress sympathetic drive, culminating in bradycardia or, in extreme cases, life-threatening arrhythmias. This mechanistic hypothesis aligns with existing knowledge of central autonomic regulation yet underscores an underrecognized risk factor warranting further mechanistic exploration.
This case report stands in stark contrast to the prevailing perception that rTMS is a benign intervention with negligible cardiovascular side effects. Historically, adverse events linked to rTMS have predominantly encompassed transient headaches, scalp discomfort, and infrequent seizure occurrence but have rarely implicated serious cardiac events. Hence, the emergence of severe arrhythmia as a possible consequence of rTMS, especially in a patient with preexisting cardiac conduction abnormalities, signals a critical paradigm shift. It raises pressing questions about pre-treatment cardiac screening protocols, risk stratification, and monitoring during rTMS therapy, particularly for patients harboring latent or overt electrophysiological vulnerabilities.
Clinicians employing rTMS must now grapple with the dual imperative of leveraging its therapeutic potential while safeguarding against inadvertent autonomic destabilization. The persistence of bradycardia despite cessation of metoprolol indicates that drug interaction alone cannot explain the cardiac outcomes observed. Instead, a more nuanced understanding of patient-specific autonomic baseline status, the neurocardiac axis, and individual susceptibility to external neuromodulation is essential. Future clinical guidelines may necessitate integrating continuous cardiac monitoring during rTMS sessions, especially in populations with known arrhythmogenic predispositions such as PVCs, atrioventricular conduction disturbances, or intrinsic sinoatrial node dysfunction.
Further research aimed at delineating the electrophysiological pathways influenced by magnetic stimulation is paramount. Advanced neuroimaging combined with simultaneous cardiac autonomic assessment could illuminate how rTMS modulates central autonomic command centers interacting with peripheral cardiac function. Moreover, animal studies and controlled human trials designed to evaluate heart rate variability, baroreflex sensitivity, and sympathetic-parasympathetic equilibrium during and after rTMS may yield invaluable insights. Such investigations would refine patient selection criteria and inspire the development of tailored neuromodulation parameters that minimize cardiovascular risks.
Importantly, this case underscores the importance of individualized medicine in psychiatric treatment realms increasingly integrating neuromodulation techniques. It beckons multidisciplinary collaboration among psychiatrists, cardiologists, and neuroscientists to optimize therapeutic outcomes while unraveling the complexities of brain-heart interactions. The neuropsychiatric community must remain vigilant to potential systemic side effects as the scope of rTMS usage expands beyond refractory depression into other neurocognitive and mood disorders.
This newfound awareness reverberates beyond clinical practice, touching ethical domains related to informed consent and patient education. Prospective rTMS candidates should be apprised not only of common side effects but also of rare, potentially serious cardiovascular risks, particularly if predisposing heart conditions exist. This transparency empowers patients to make fully informed decisions and encourages prompt reporting of unusual symptoms.
In conclusion, the documented case of severe bradycardia induced by rTMS in a patient with MDD and PVCs challenges the current dogma surrounding the cardiovascular safety of neuromodulation therapies. While rTMS remains a cornerstone in treating resistant depression, its interaction with cardiac autonomic regulation demands rigorous scrutiny. This report lays the groundwork for expanding cardiac safety monitoring protocols and stimulates urgent research to decode the mechanistic underpinnings linking cortical magnetic stimulation to arrhythmogenic outcomes. It is a compelling reminder that even the most promising innovations in neuropsychiatry may harbor unanticipated systemic effects, reinforcing the need for comprehensive vigilance in clinical application.
Subject of Research: Cardiovascular effects of repetitive transcranial magnetic stimulation (rTMS) in psychiatric patients with arrhythmias.
Article Title: Severe bradycardia triggered by repetitive transcranial magnetic stimulation in a patient with major depressive disorder and premature ventricular contractions: a case report.
Article References:
Fang, S., Song, B., Yang, X. et al. Severe bradycardia triggered by repetitive transcranial magnetic stimulation in a patient with major depressive disorder and premature ventricular contractions: a case report.
BMC Psychiatry 25, 441 (2025). https://doi.org/10.1186/s12888-025-06882-5
Image Credits: AI Generated
