Neuroleptic Malignant Syndrome Research Articles

Atypical Antipsychotics Use and Neuroleptic Malignant Syndrome: A Review With a Clinical Perspective

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening idiosyncratic reaction associated with the use of antipsychotic medications, characterized by hyperthermia, muscle rigidity, and alterations in consciousness. Despite a reduction in its incidence due to the predominance of atypical antipsychotics in contemporary treatment regimens, NMS remains a critical neuropsychiatric emergency that warrants vigilant attention. There is a hypothesis proposing that catatonia and NMS may exist along a continuum of the same disorder, and evidence suggests that lorazepam may offer therapeutic benefits for both conditions. It is potential for the concurrent occurrence of NMS and serotonin syndrome when antipsychotics and antidepressants are administered concomitantly. This paper presents a case of NMS following the reinitiation of antipsychotic treatment over an extended duration, a scenario inadequately addressed in existing reports, and discusses strategies for its management in clinical practice.

Bipolar Disorder in a Young Adult With Thalassemia Major With Sequential Development of Neuroleptic Malignant Syndrome and Serotonin Syndrome.

Bipolar Disorder in a Young Adult With Thalassemia Major With Sequential Development of Neuroleptic Malignant Syndrome and Serotonin Syndrome.

Neuroleptic malignant syndrome in Huntington disease.

Despite the wide use of dopamine receptor blocking agents (DRBAs) in Huntington disease (HD), neuroleptic malignant syndrome (NMS) is rarely described in this population. The aim of this study was to assess NMS prevalence in a large cohort of HD patients and explore the main associated risk factors. In 2023, an HD patient was admitted to our neurology department due to NMS. Starting from the case description, we performed a narrative review of the literature of NMS cases in HD, reviewed data from the fifth dataset of the Enroll-HD (a longitudinal, observational, global study of families with HD) study (PDS5) selecting HD patients treated with DRBAs and/or tetrabenazine (TBZ) who presented at least one of the core symptoms of NMS (rigidity and hyperthermia), and collected data to investigate prevalence of NMS and identify risk factors. In the Enroll-HD PDS5 dataset, we identified 5108 of 11,569 HD patients who were undergoing DRBA and/or TBZ treatment. Only one patient, a Caucasian man of 46 years, undergoing clozapine and valproate treatment, had a registered diagnosis of NMS. NMS in HD patients is seldom described. This could be due to an underestimation of this condition. There are no available objective NMS diagnostic criteria at present, and the existence of atypical forms of NMS further complicates diagnosis. Advanced disease stage, rigid-akinetic phenotype, abrupt therapy changes, polytherapy, and dehydration are key risk factors, most of which are preventable through awareness and caution in managing medications in the HD population.

Psychiatric Etiologies and Approaches in Altered Mental Status Presentations: Insights from Consultation Liaison Psychiatry.

Consultation liaison psychiatrists are frequently asked to evaluate patients with altered mental status (AMS). Psychiatrists have unique perspectives and approaches to care for confused patients, particularly optimizing facilitation of care and maintaining vigilance for diagnostic overshadowing. Psychiatrists also offer expertise in primary psychiatric illnesses that can overlap with AMS, and the most common etiology of AMS is delirium. In this article, we provide a consultation liaison psychiatrist perspective on AMS and related psychiatric conditions in addition to delirium. Manic and psychotic episodes have primary and secondary etiologies, with some symptoms that can overlap with delirium. Catatonia, neuroleptic malignant syndrome, and serotonin syndrome are potentially fatal emergencies, and require prompt index of suspicion to optimize clinical outcomes. Trauma sequelae, functional neurologic disorders, and dissociative disorders can present as puzzling cases that require psychiatric facilitation of care. Additionally, AMS is sometimes due to substance intoxication and withdrawal in the hospital. A nonstigmatizing approach to evaluation and management of delirium and AMS can ensure optimal patient care experiences and outcomes.

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.

Neuroleptic Malignant Syndrome with Low-dose Quetiapine After Venlafaxine Withdrawal: A Case Report.

Neuroleptic Malignant Syndrome (NMS) is an idiosyncratic and potentially life-threatening drug reaction. Although uncommon, NMS cases induced by oral quetiapine have been reported. Most reports have predisposing risk factors such as an organic brain disorder, concomitant use of other antipsychotics or lithium, overdose or rapid titration. NMS with low doses of quetiapine is a much rarer clinical picture. Venlafaxine is commonly associated with withdrawal upon discontinuation sometimes as soon as the next day. In this case report, a 40-year-old man treated with venlafaxine for generalized anxiety disorder with symptoms of full-blown NMS after venlafaxine withdrawal, induced by low-dose quetiapine (50 mg), is presented. In accordance with the previous reports, we speculate that venlafaxine withdrawal was a predisposing factor in our case however we also discussed other possible explanations for NMS. Acknowledging the risk of NMS, even with low doses of quetiapine in patients devoid of known risk factors, is of paramount importance for prompt diagnosis and mitigating morbidity and mortality. To our knowledge, this is the first case of NMS with such a low dose of quetiapine without any other known risk factors or substances. Keywords: Antipsychotics, NMS, Quetiapine, Venlafaxine, Consultation Liaison Psychiatry.

Pancytopenie en drug fever bij olanzapine

Olanzapine-induced pancytopenia and drug fever Olanzapine is a frequently used antipsychotic. Despite the structural similarity, olanzapine is considered a safer alternative for clozapine in terms of side effects. Hematological suppression, particularly neutropenia, is generally not associated with olanzapine. Furthermore, fever in the absence of a malignant neuroleptic syndrome is not an expected side effect of olanzapine. This case reports the occurrence of olanzapine-induced pancytopenia and fever in a 74-year-old woman with acute psychosis. Both side effects developed a few days after starting olanzapine and resolved after its discontinuation. Extensive investigations did not reveal any satisfactory alternative explanation for both phenomena. This article describes other cases with similar findings and discusses the possible pathogenesis. This case, in addition to other case reports, suggests that olanzapine can also lead to hematological suppression. Whether hematological monitoring, as with clozapine, is required, needs further investigation. Furthermore, this case illustrates that fever can occur with olanzapine in the absence of a malignant neuroleptic syndrome. Increased vigilance for both side effects is therefore indicated.

Incidence of Neuroleptic Malignant Syndrome During Antipsychotic Treatment in Children and Youth: A National Cohort Study.

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5-24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004-2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18-24 years (HR [95% CI] = 2.45 [1.65-3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16-10.88]), neurodevelopmental disorders (HR = 7.11 [4.02-12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15-2.54]), and first-generation antipsychotics (HR = 4.32 [2.74-6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1-3.0) for those with none of these factors to 198.1 (132.8-295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5-17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18-24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes.

Conceptualizing the relationship between synthetic cannabinoid use and neuroleptic malignant syndrome.

Conceptualizing the relationship between synthetic cannabinoid use and neuroleptic malignant syndrome.

Evaluation of Antipsychotic-Induced Neuroleptic Malignant Syndrome Using a Self-Organizing Map.

Introduction In neuropsychiatric pharmacotherapy, neuroleptic malignant syndrome (NMS) is a potentially serious side effect of antipsychotics characterized primarily by fever, disorientation, extrapyramidal disorders, and autonomic nervous system imbalance, which can lead to death if left untreated. We visualized the NMS profile of antipsychotics using a self-organizing map (SOM). We combined it with decision tree analysis to discriminate between 31 antipsychotics in more detail than typical antipsychotic (TAP) and atypical antipsychotic (AAP) classifications. Method A total of 20 TAPs and 11 AAPs were analyzed. We analyzed NMS reports extracted from the Japanese Adverse Drug Event Report (JADER) database based on standardized Medical Dictionary for Regulatory Activities (MedDRA) queries (Standardized MedDRA Queries (SMQ) code: 20000044, including 68 preferred terms). The SOM was applied using the SOM package in R version 4.1.2 (RFoundation for Statistical Computing, Vienna, Austria). Results The Japanese Adverse Drug Event Report (JADER) database contained 887,704 reports published between April 2004 and March 2024. The numbers of cases of NMS (SMQ code: 20000044) reported for risperidone, aripiprazole, haloperidol, olanzapine, and quetiapine were 1691, 1294, 1132, 1056, and 986, respectively. After the antipsychotics were classified into six units using SOM, they were adapted for decision tree analysis. First, 31 antipsychotics branched off into groups with loss of consciousness, with one group (10 TAPs) consisting entirely of TAPs, and the other consisting of antipsychotics that were further separated into two groups with coma induced by TAPs and AAPs. Conclusion The results of this study provide a reference for healthcare providers when predicting the NMS characteristics induced by each drug in patients, thereby facilitating the effective treatment of schizophrenia.

Anti-NMDAR Encephalitis developing neuroleptic malignant syndrome.

Anti-NMDAR Encephalitis developing neuroleptic malignant syndrome.

Concomitant Administration of Ozanimod and Serotonergic Antidepressants in Patients With Ulcerative Colitis or Relapsing Multiple Sclerosis.

Ozanimod, approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS), is a weak in vitro monoamine oxidase B (MAO-B) inhibitor. MAO-B inhibitors can cause serotonin accumulation with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs). We evaluated the incidence of treatment-emergent adverse events (TEAEs) potentially associated with serotonin accumulation during ozanimod and concomitant SSRI/SNRI use in this post hoc analysis of pooled UC studies and the open-label extension RMS DAYBREAK. Data for ozanimod 0.92mg from pooled UC studies (n = 1158; cutoff: January 10, 2022) and RMS DAYBREAK (n = 2257; cutoff: February 1, 2022) were analyzed. Concomitant SSRI/SNRI use was allowed in the UC (n = 67) and RMS (n = 274) studies. A narrow Medical Dictionary for Regulatory Activities search ("serotonin syndrome," "neuroleptic malignant syndrome," and "malignant hyperthermia") and a broad search including terms potentially associated with serotonin accumulation were conducted. The percentages of patients with TEAEs in both searches were analyzed by concomitant SSRI/SNRI use when the TEAE occurred. No patients had TEAEs matching the narrow search criteria. No differences were observed in the percentages of patients with ≥1 TEAE matching the broad search regardless of SSRI/SNRI use in UC (with: 25.4% [n = 17 of 67]; without: 15.0% [n = 164 of 1091]) and RMS (with: 12.4% [n = 34 of 274]; without: 15.6% [n = 310 of 1982]) studies. No evidence of increased TEAEs potentially associated with serotonin accumulation was observed with concurrent use of ozanimod and SSRIs/SNRIs. NCT01647516, NCT02531126, NCT02435992, NCT02576717.

A Series of Eight Cases of Pigment Nephropathy: An Obscured Aspect of Acute Kidney Injury.

Pigment-induced acute kidney injury (AKI) is an important and preventable complication of rhabdomyolysis or hemolysis. It is characterized by the release of free heme pigment (myoglobin or hemoglobin) in the circulation, leading to direct injury of the proximal tubuleand distal tubule obstruction by pigment cast. We are reporting eight cases of pigment-induced AKI, including six cases of myoglobin cast nephropathy and two cases of hemoglobin cast nephropathy.The causes of rhabdomyolysis were strenuous exercise, infection/febrile illness, and drug-induced neuroleptic malignant syndrome. Paroxysmal nocturnal hemoglobinuria and anti-tuberculosis treatment (rifampicin and isoniazid) had led to hemoglobin cast nephropathy each in one case. Seven cases had severe renal failure requiring dialysis.Short-term renal outcome was favorable. However, long-term follow-up is necessary to determine whether pigment-induced AKI has delayed sequelae. Therefore, clinicians should consider rhabdomyolysis or hemolysis as potential hidden causes of AKI in diverse clinical conditions, especially those of non-traumatic origin, to achieve an accurate diagnosis.

Neuroleptic malignant syndrome presenting without hyperthermia: A case report of an atypical presentation

Neuroleptic malignant syndrome (NMS) is a life-threatening complication of antipsychotic medications. NMS is characterized by four key symptoms: Changes in mental status, muscular rigidity, hyperthermia, and autonomic dysfunction. Despite its key clinical symptoms, which are easily recognizable in a classic presentation, NMS occasionally does not present with all the described clinical characteristics. Atypical presentations of NMS pose a diagnostic conundrum for clinicians, leading to late recognition and treatment of a potentially treatable life-threatening condition. We present a case of NMS presenting without hyperthermia and autonomic instability but with elevated creatine kinase.

Use of En-Bloc Multiple Monitored Electroconvulsive Therapy in Benzodiazepine Refractory Malignant Catatonia.

We report a case of an adolescent female experiencing benzodiazepine and single-stimulation electroconvulsive (ECT)-refractory malignant catatonia, who improved with the use multiple monitored ECT (mmECT). Per the 2001 American Psychiatric Association guidelines, mmECT should be considered only in cases of intractable seizures or neuroleptic malignant syndrome. Since 2001, neuroleptic malignant syndrome and malignant catatonia have been described as occurring along the same spectrum of illness. Therefore, given the life-threatening nature of her condition, as well as the brief seizure duration she experienced from single-stimulation ECT, the patient was treated with en-bloc and 2-stimulation mmECT. The patient demonstrated a significant improvement in response to this treatment, with her Bush-Francis Catatonia Rating Scale score decreasing by 89%. At 2-year follow-up in an outpatient neurodevelopmental catatonia clinic, the patient has been able to return to school in her previous advanced placement classes and has not required maintenance ECT.

Atypical Antipsychotics and Lithium Induced Neuroleptic Malignant Syndrome associated with Acute Kidney Injury: A Case Report

Neuroleptic Malignant Syndrome (NMS) is a rare but serious adverse reaction to antipsychotic medications. This case report presents a 56-year-old male with bipolar disorder on a regimen of Olanzapine, Clozapine and Lithium carbonate, who developed typical NMS. He had muscle rigidity, hyperthermia, rhabdomyolysis which led to acute kidney injury. Prompt withdrawal of psychotropic medications and administration of supportive therapies was done, yet the patient's condition deteriorated, leading to Multiple Organ Dysfunction Syndrome (MODS) and eventually mortality. This case shows the complexity of managing NMS in the context of polypharmacy emphasizing the need for vigilance when prescribing antipsychotic combinations and the challenges faced in treating NMS, especially when there are associated complications.

Neuroleptic malignant syndrome in puerperal women

Introduction Neuroleptic malignant syndrome is an rare event, even more so among patient from puerperal period. The incidence risk is of 0.11%. It is often occurs when a patient is prescribed on antipsychotic for long duration of time. Case Report We report a case of a female patient, two weeks in post natal period presented with altered behaviour at home. She has prior admission being treated for post partum psychosis with anti psychotic. However antipschotic was withheld as she developed extrapyramidal symptoms while in ward. At home, she developed fever, altered sensorium and fitting-like-episode. On arrival patient was unresponsive and with features of impaired airway patency. Her had unstable vital sign with elevated blood pressure, heart rate and temperature. Brain imagine came back normal, excluding brain pathology. She was diagnosed as neuroleptic malignant syndrome as fulfilled features of elevated creatine kinase. She was treated symptomatic by providing first aid to reduce temperature and started on benzodiazepines. She was subsequently admitted to intensive ward and responded well to treatment Conclusion Physician must be familiar and have high index of suspicious to identify and treat neuroleptic malignant syndrome. Without prompt treatment, it is highly fatal.

Successful Treatment of Both Refractory Neuroleptic Malignant Syndrome and Subsequent Catatonia With Electroconvulsive Therapy in a Patient With Suspected Kufs Disease.

We describe a patient suffering from probable Kufs disease who developed a neuroleptic malignant syndrome (NMS) after use of an antipsychotic agent over some weeks during hospitalization due to neuropsychiatric symptoms. Transferred to the neurology department, the patient quickly developed catatonic features. She did not respond to usual medical treatment but did respond to electroconvulsive therapy (ECT). The patient worsened following a nosocomial SARS-CoV-2 infection but improved again during a second course of ECT. We discuss Kufs disease as a potential risk factor for NMS and address the link between NMS and catatonia as well as the indication for ECT in both disorders. We also discuss the impact of SARS-CoV-2 infection on the clinical outcome. We describe the long recovery process and the secondary worsening of the patient on a cognitive level.

Neuroleptic malignant syndrome and serotonin syndrome: a comparative bibliometric analysis

ObjectiveThis study aimed to analyze and map scientific literature on Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS) from prestigious, internationally indexed journals. The objective was to identify key topics, impactful articles, prominent journals, research output, growth patterns, hotspots, and leading countries in the field, providing valuable insights for scholars, medical students, and international funding agencies.MethodsA systematic search strategy was implemented in the PubMed MeSH database using specific keywords for NMS and SS. The search was conducted in the Scopus database, renowned for its extensive coverage of scholarly publications. Inclusion criteria comprised articles published from 1950 to December 31st, 2022, restricted to journal research and review articles written in English. Data were analyzed using Microsoft Excel for descriptive analysis, and VOSviewer was employed for bibliometric mapping.ResultsThe search yielded 1150 articles on NMS and 587 on SS, with the majority being case reports. Growth patterns revealed a surge in NMS research between 1981 and 1991, while SS research increased notably between 1993 and 1997. Active countries and journals differed between NMS and SS, with psychiatry journals predominating for NMS and pharmacology/toxicology journals for SS. Authorship analysis indicated higher multi-authored articles for NMS. Top impactful articles focused on review articles and pathogenic mechanisms. Research hotspots included antipsychotics and catatonia for NMS, while SS highlighted drug interactions and specific medications like linezolid and tramadol.ConclusionsNMS and SS represent rare but life-threatening conditions, requiring detailed clinical and scientific understanding. Differential diagnosis and management necessitate caution in prescribing medications affecting central serotonin or dopamine systems, with awareness of potential drug interactions. International diagnostic tools and genetic screening tests may aid in safe diagnosis and prevention. Reporting rare cases and utilizing bibliometric analysis enhance knowledge dissemination and research exploration in the field of rare drug-induced medical conditions.

A Case of Overlapping Extrapyramidal Side Effects and Neuroleptic Malignant Syndrome

A Case of Overlapping Extrapyramidal Side Effects and Neuroleptic Malignant Syndrome