Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective

Abstract

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening sideeffect that can occur in response to treatment with antipsychotic drugs. Symptoms commonly include hyperpyrexia, muscle rigidity, autonomic dysfunction and altered mental status. In the current review we provide an overview on past and current developments in understanding the causes and treatment of NMS. Studies on the epidemiological incidence of NMS are evaluated, and we provide new data from the Canada Vigilance Adverse Reaction Online database to elaborate on drug-specific and antipsychotic drug polypharmacy instances of NMS reported between 1965 and 2012. Established risk factors are summarized with an emphasis on pharmacological and environmental causes. Leading theories about the etiopathology of NMS are discussed, including the potential contribution of the impact of dopamine receptor blockade and musculoskeletal fiber toxicity. A clinical perspective is provided whereby the clinical presentation and phenomenology of NMS is detailed, while the diagnosis of NMS and its differential is expounded. Current therapeutic strategies are outlined and the role for both pharmacological and non-pharmacological treatment strategies in alleviating the symptoms of NMS are discussed.

Neurotoxicity and nephrotoxicity caused by combined use of lithium and risperidone: a case report and literature review

“…All cases developed neurotoxicity with symptoms of lethargy, delirium, and even neuroleptic malignant syndrome (NMS) (4 of 7 cases). NMS is characterized by delirium, muscular rigidity, fever, and autonomic nervous system dysregulation with typically high levels of creatine phosphokinase but not necessary in elevation of creatinine [13, 14]. Furthermore, our report specially showed the change of renal function in detail compared to previous reports.…”

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

“…NMS can occur with both FGAs and SGAs, in particular with the typical antipsychotics flupentixol, HAL, fluphenazine, thioridazine, CPZ, trifluoperazine, LOX, periciazine, methotrimeprazine, prochlorperazine, and zuclopenthixol, as well as with CLO, OLA, RIS, QUE, ARI, PALI, ASE, and ZIP 230. While no clear consensus exists,230 SGA-associated NMS seems to be of lower frequency, severity, duration, and lethality than NMS associated with FGAs 231,232. CLO may have the highest risk of NMS among SGAs,230 although patient-related factors may also play a role.…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…While generally unpredictable, the risk is greatest during the initial phase of treatment or change of dosage, with intravenous or intramuscular administration, with high dosages or polypharmacy, when the patient is physically restrained or dehydrated, in high ambient temperatures, in older patients and in patients with medical or psychiatric comorbidities. Patients with a previous history of NMS and/or a personal or family history of catatonia are also at higher risk 867. Antipsychotics may also impact thermoregulation, with case studies indicating the potential for both heat‐related illnesses868 and hypothermia869; thus, patients should be made aware and monitored for these risks during periods of extreme temperatures.…”