The subject of the report centers around a 20-year-old female patient grappling with a severe major depressive episode paired with psychotic features, characterized by a relentless barrage of 10 to 12 suicidal command hallucinations daily. Her clinical course was notably precarious, featuring four suicide attempts within a single week. Despite aggressive pharmacological interventions involving three different antipsychotics—Aripiprazole, Olanzapine, and Risperidone—and a full course of 12 electroconvulsive therapy (ECT) sessions, her symptoms demonstrated stubborn resistance, underscoring the urgent need for alternative interventions.

Stereotactic lesioning, an advanced neurosurgical technique, offers a high-precision method to target specific brain regions implicated in psychiatric pathology. In this patient’s case, bilateral lesioning was performed on the anterior limb of the internal capsule and the cingulate gyrus (SALIC-CG). These brain structures are critically involved in emotional regulation, cognitive control, and integration of complex sensory information, making them strategic targets for interrupting the pathological neural circuits responsible for the patient’s distressing hallucinations.

Remarkably, within only one week following the stereotactic intervention, the patient exhibited profound symptom relief. Clinical rating scales provided quantitative evidence of this improvement: the Montgomery-Asberg Depression Rating Scale (MADRS) score plummeted from a severe 30 to a mild 7, and the Hoffman auditory hallucination score dropped sharply from 25 down to zero. Such rapid remission highlights the potential of stereotactic lesioning to disrupt the neural underpinnings of refractory psychosis, offering renewed hope for patients in otherwise dire clinical scenarios.

However, the course of disease and treatment revealed a critical insight regarding the necessity of adjunctive pharmacotherapy post-surgery. One month after the lesioning procedure, the patient abruptly discontinued Risperidone, an antipsychotic previously deemed ineffective when used in isolation. This cessation correlated with a dramatic relapse; MADRS and Hoffman scores surged back to 22 and 20, respectively. The re-emergence of severe symptomatology upon withdrawal of medication signifies that while stereotactic surgery offers a potent initial intervention, sustained symptom control is intricately dependent on continued pharmacologic management.

Reinstatement of Risperidone therapy precipitated rapid symptom remission, ultimately maintaining the patient in stable remission at six months follow-up, with a MADRS score of 6 and a complete absence of hallucinations. This observation fundamentally challenges existing paradigms that consider pharmacotherapy as merely ancillary to surgical interventions in psychiatric disorders. Instead, it advocates for an integrated “surgery plus long-term pharmacotherapy” treatment model, underscoring the synergistic relationship between precise neurosurgical disruption of pathological circuits and ongoing receptor-level modulation offered by antipsychotics.

The implications of this unique case report extend far beyond a single individual. Refractory suicidal command hallucinations embodied within psychotic major depressive episodes pose an acute clinical emergency with high mortality risk and limited therapeutic options hitherto. The demonstrated efficacy of stereotactic lesioning in conjunction with sustained Risperidone maintenance introduces a potentially life-saving approach and calls for deeper exploration into neurobiological mechanisms that permit remission through combined modalities.

From a neuroscientific perspective, the anterior limb of the internal capsule and cingulate gyrus represent nodes of convergence for fronto-subcortical circuits regulating mood, executive function, and perceptual integration. Targeted lesioning in these areas may interrupt the maladaptive feedback loops perpetuating psychotic command hallucinations, which are typically refractory to pharmacotherapeutic blockade of dopamine receptors alone. The synergistic effect of surgical disconnection and antipsychotic receptor antagonism could modulate neural plasticity and synaptic signaling pathways in a manner unachievable by either treatment independently.

Beyond the technical achievements and clinical outcomes, this case also underscores the critical importance of vigilant postoperative management. Abrupt discontinuation of Risperidone reversed the benefits of an otherwise successful surgery, revealing an essential clinical principle: the neurologic and psychiatric sequelae following stereotactic intervention require carefully calibrated pharmacological oversight, tailored to sustain remission and prevent relapse. This insight commands a reevaluation of post-surgical care protocols in psychiatric neurosurgery.

While still preliminary, the findings also raise significant ethical and procedural considerations regarding the utilization of stereotactic lesioning. As a relatively invasive procedure reserved traditionally for treatment-refractory neurological disorders such as Parkinson’s disease or obsessive-compulsive disorder, its application in psychiatric emergencies demands meticulous patient selection, stringent consent processes, and long-term follow-up studies to assess safety profiles and quality of life outcomes.

As psychiatric medicine continuously evolves, this report highlights that innovative combinations of neurosurgical technology and psychopharmacology can redefine treatment horizons for patients with the gravest neuropsychiatric conditions. The narrative of this young woman’s recovery serves as a compelling call to action for clinical trials and expanded research into integrated therapies that bridge brain circuitry modification and receptor-level modulation for complex depressive psychosis.

Ultimately, this case sets a scientific and clinical precedent with profound implications: the fusion of stereotactic lesioning with sustained pharmacologic maintenance may emerge as a transformative therapeutic avenue, providing new hope for individuals ensnared in the catastrophic interplay of psychosis, depression, and suicidality. As researchers and clinicians digest these findings, the psychiatric field stands on the cusp of redefining approaches that might soon save countless lives otherwise destined for tragedy.

Subject of Research: Refractory suicidal command hallucinations in major depressive episode with psychotic features; stereotactic lesioning combined with long-term antipsychotic maintenance therapy.

Article Title: Stereotactic lesioning combined with long-term Risperidone maintenance for life-threatening refractory suicidal command hallucinations in major depressive episode with psychotic features: a case report.

Article References: Chen, C., Li, R., Bai, H. et al. Stereotactic lesioning combined with long-term Risperidone maintenance for life-threatening refractory suicidal command hallucinations in major depressive episode with psychotic features: a case report. BMC Psychiatry (2025). https://doi.org/10.1186/s12888-025-07627-0

Image Credits: AI Generated

DOI: https://doi.org/10.1186/s12888-025-07627-0

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

DOI: https://doi.org/10.1186/s12888-025-06882-5