Neuroleptic malignant syndrome: Diagnostic and therapeutic approach. Narrative review
Abstract
Neuroleptic malignant syndrome (NMS) is an uncommon but potentially life-threatening neuropsychiatric emergency primarily associated with antipsychotic therapy and, less frequently, with the withdrawal of dopaminergic medications. This narrative review summarizes and discusses the current clinical evidence on the epidemiology, risk factors, pathophysiology, differential diagnosis, treatment, and outcomes of NMS, with a focus on its practical implications for clinical decision-making.
A comprehensive review of the published literature was conducted, including case reports, case series, observational studies, pharmacovigilance analyses, systematic reviews, and clinical practice guidelines. The available evidence was qualitatively synthesized to identify the most relevant findings. NMS is characterized by hyperthermia, severe muscle rigidity, altered mental status, and autonomic dysfunction, although its clinical presentation is often heterogeneous. Its development appears to result from the interaction of patient-related factors, such as medical comorbidities, catatonia, and dehydration; pharmacological factors, including high dopamine D2 receptor antagonism, rapid dose escalation, and the use of long-acting injectable antipsychotics; and contextual factors, such as agitation, physical restraint, and concomitant infections. Management is based on the immediate discontinuation of the offending agent, intensive supportive care, and, in selected cases, the administration of dantrolene, dopamine agonists, and electroconvulsive therapy performed under general anesthesia with neuromuscular blockade in patients with refractory NMS or concomitant malignant catatonia. Early recognition and the implementation of standardized management protocols are essential to reduce mortality and long-term sequelae. However, important knowledge gaps remain regarding the safe reintroduction of antipsychotics, differences in risk between first- and second-generation antipsychotics, and the impact of specific medical comorbidities.
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