In a groundbreaking study published in BMC Psychiatry, researchers explore the nuanced effects of ultra-brief pulse electroconvulsive therapy (ECT) on postoperative delirium in patients diagnosed with schizophrenia (SCZ). This investigation offers vital insights into how ultra-brief pulse (UBP) ECT compares to traditional brief pulse (BP) ECT in minimizing the cognitive side effects commonly associated with this psychiatric treatment. The study probes not only clinical outcomes but also the underlying biochemical and neural mechanisms linked to delirium, a frequently observed and debilitating complication.
Electroconvulsive therapy has long been a critical tool in the psychiatrist’s arsenal, especially for treatment-resistant psychiatric conditions. However, its side effects, particularly postoperative delirium, have often clouded its acceptance and application. Delirium can severely hinder recovery, manifesting as acute confusion and cognitive disturbance. The present study focuses on whether modifying the pulse duration of ECT can lower the risk of such complications, thereby refining its safety profile while maintaining therapeutic efficacy.
Conducted from August 2022 to August 2023, the study enrolled inpatients aged 18 to 55 from the Affiliated Brain Hospital of Nanjing Medical University, all formally diagnosed with SCZ under the International Statistical Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10). The participants were randomized into two groups, receiving either ultra-brief pulse ECT with a pulse width of 0.25 milliseconds or brief pulse ECT with a wider pulse of 1.0 millisecond. This design allowed for a meticulous head-to-head comparison between two distinct ECT protocols.
Patient evaluation extended beyond mere clinical observation. Delirium was rigorously assessed using validated scales including the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the Intensive Care Unit (ICU-CAM). Simultaneously, magnetic resonance spectroscopy (MRS) provided precise measurements of hippocampal neural metabolites — such as N-acetyl-aspartate (NAA), creatinine (Cr), myo-inositol (MI), and choline (Cho) — offering a deeper window into neurochemical changes induced by ECT.
Crucially, the researchers also monitored an array of serum markers to understand the inflammatory and cholinergic landscape post-ECT. This battery involved twelve distinct cytokines, C-reactive protein (CRP), and cholinesterase (ChE). The latter enzyme plays a pivotal role in modulating cholinergic neurotransmission and has been linked to cognitive function and delirium pathogenesis, making it an indispensable biomarker in this context.
The results illuminated fascinating differences between the two groups. Demographically and clinically, the groups were well matched at baseline with no statistically significant differences, ensuring that variations observed post-treatment could be attributed to the ECT pulse protocol itself. Incidence of delirium was notably lower in the UBP group compared to the BP group, with chi-square analysis yielding a p-value of 0.046, signaling a significant benefit from the ultra-brief pulse approach.
Neurochemical data from hippocampal MRS scans revealed that NAA to creatinine and NAA to myo-inositol ratios — indicators of neuronal integrity and glial activity respectively — were reduced post-treatment more in the UBP group. This might suggest differential neural responses to pulse width modulation, possibly reflecting altered metabolic demands or synaptic activity patterns. Such neurophysiological insights are crucial for understanding how ECT influences brain function on a microscopic level.
Perhaps even more compelling were the inflammatory and cholinergic markers. The UBP cohort demonstrated significantly higher cholinesterase levels, a finding that aligns with reduced cholinergic disruption and may partially mediate the reduced delirium incidence. Simultaneously, levels of CRP and pro-inflammatory cytokines such as IL-6, IL-8, IL-10, IL-1β, and TNF-α were substantially lower in the UBP group. This attenuation of the inflammatory response lends strong credence to the hypothesis that ultra-brief pulses minimize neuroinflammation, a recognized contributor to cognitive dysfunction including delirium.
The implications of these findings stretch far beyond mere modification of pulse width. They suggest a more refined neurobiological mechanism where ultra-brief pulses might curtail aberrant neuronal asynchronous depolarization, which could otherwise perturb cholinergic signaling and provoke inflammatory cascades. This provides a mechanistic basis for the clinically observed reduction in delirium without compromising the antidepressant and antipsychotic efficacy of ECT.
Furthermore, this study underscores the potential of tailored ECT protocols designed not only with efficacy in mind but also with the minimization of cognitive side effects, which have historically marred the therapy’s reputation. Such innovations could revolutionize psychiatric treatment paradigms for schizophrenia, offering safer modalities that enhance patient compliance and improve overall outcomes.
While the study is robust in methodology and scope, future research is necessary to replicate these results in larger and more diverse populations, including longitudinal assessments to track longer-term cognitive and functional outcomes. Understanding the dynamics of hippocampal metabolite changes and inflammatory modulation over time will be vital to optimizing ECT parameters further.
In clinical practice, this research could prompt psychiatrists to increasingly favor ultra-brief pulse ECT, especially for patients considered at higher risk for delirium or those with pronounced inflammatory profiles. Personalized medicine approaches could emerge, integrating neurochemical biomarkers with clinical characteristics to customize ECT pulse parameters, maximizing benefits while minimizing adverse effects.
Overall, this investigation deepens our understanding of the biological interplay between ECT modalities, cholinergic neurotransmission, and neuroinflammation, shedding light on the elusive pathophysiology of delirium. Its findings are poised to influence future clinical guidelines and research trajectories, emphasizing patient safety without sacrificing therapeutic potency.
In sum, the study heralds a promising advance in psychiatric care by demonstrating that ultra-brief pulse electroconvulsive therapy significantly reduces delirium incidence in schizophrenia patients, likely through modulation of cholinesterase activity and inflammatory mediators. This dual impact on neurophysiology and clinical outcomes represents a crucial step forward in the evolution of ECT as a precision psychiatric intervention.
Subject of Research: The investigation of delirium side-effects following ultra-brief pulse electroconvulsive therapy in patients with schizophrenia, focusing on clinical outcomes, hippocampal metabolites, cholinesterase levels, and inflammatory markers.
Article Title: The study on delirium side-effects after ultra-brief pulse electroconvulsive therapy
Article References:
Guo-Xin, X., Run-Da, L., Pei-Yu, C. et al. The study on delirium side-effects after ultra-brief pulse electroconvulsive therapy. BMC Psychiatry 25, 634 (2025). https://doi.org/10.1186/s12888-025-07037-2
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