Atypical Neuroleptic Malignant Syndrome Research Articles

Atypical antipsychotic-induced neuroleptic malignant syndrome

The rare neuroleptic malignant syndrome (NMS) is associated with early mortality of >30%. Better supportive care has reduced mortality to <10%. Atypical antipsychotics such as clozapine and risperidone are associated with an atypical but potentially lethal, NMS. A 22-year-old male developed NMS after being treated with clozapine and risperidone for aggression associated with mental retardation for about 8 years. For the past 1 year, the dose of clozapine was 200 mg/day and the dose of risperidone was 8 mg/day. The patient presented with symptoms of hyperthermia, perspiration, neck rigidity, and tonic posturing of all four limbs with tongue bite and frothing from the mouth. On examination, the patient’s Glasgow coma Scale was E3V1M4. He was intubated and given antibiotics, antiepileptic, tablet bromocriptine 2.5 mg (1-1-1-1), and other supportive treatment. The patient showed improvement in 10 days. Knowledge of diagnostic features, risk factors, treatment modalities, and differential diagnosis of NMS is essential. Early diagnosis and prompt treatment can reduce mortality and morbidity significantly.

Neuroleptic Malignant Syndrome in Patients With Dementia: Experiences of A Single Memory Clinic.

Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course. The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay. Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died. This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.

Serotonin Syndrome: The Role of Pharmacology in Understanding Its Occurrence.

Serotonin syndrome (SS) is a potentially fatal adverse drug reaction characterized by an exaggerated increase in serotonergic activity in the central and peripheral nervous systems. It presents a constellation of signs and symptoms related to behavioral changes, neuromuscular excitability, and autonomic instability. These symptoms can occur in both mild and severe forms. SS can be triggered by the therapeutic use of a drug that increases serotonin (5-HT) availability in the synaptic cleft or by the co-administration of two or more drugs that provide this increase. With the escalating use of antidepressants by the world's population, this adverse reaction may be more recurrent. However, SS is often overlooked by patients or not diagnosed by doctors. This review aims to improve awareness about SS and provide a pharmacological perspective to explain its occurrence. Evidence shows that other neurotransmitters may also be involved with the pathology of SS. Furthermore, SS and neuroleptic malignant syndrome (NMS) seem to be part of the same pathological spectrum, especially in atypical NMS cases. The emergence of the syndrome's symptoms may be closely related to pharmacokinetic and/or pharmacodynamic polymorphisms that lead to an increase in the 5-HT available to or 5-HT signaling by specific receptors, thus constituting an important area for future investigations.

Atypical Presentations of Neuroleptic Malignant Syndrome: Diagnostic Challenge

Introduction: Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, potentially fatal disease that can present with an atypical clinical picture that refers to subthreshold presentations of NMS. The aim of our study is to shed light on the atypical presentations of neuroleptic malignant syndrome by highlighting the different clinical and biological features of this entity that may be underestimated or confused with a differential diagnosis. Materials and Methods: A descriptive study that retrospectively studied the clinical characteristics and laboratory results of patients with a diagnosis of neuroleptic malignant syndrome; the patients were divided into two groups: typical malignant syndrome and atypical NMS. All data were transferred and analyzed using SPSS 13.0 software. Results: The Amisulpride was the most frequently implicated drug (n = 36.6%), most patients were male (21 males versus 9 females). The majority of patients had psychosis, there were no statistically significant differences in terms of age, clinical and laboratory characteristics, but in the atypical NMS group both gender were affected with comparable rates, more than half of the patients in the atypical NMS group had no rigidity with no fever and no disturbance of consciousness and creatine kinase (CK)values lower than those observed in the typical NMS group. The evolution was favorable in the atypical NMS group compared to the typical NMS group in which one death was noted and 5 patients were transferred to intensive care. Conclusion: Neuroleptic malignant syndrome is a fatal complication. Clinicians must be vigilant while carefully assessing the features of NMS in a patient on antipsychotics even in the absence of cardinal signs such as rigidity and fever. Furthermore, the need to adopt a spectrum concept of NMS to challenge the underdiagnosis and misdiagnosis of this fatal entity is of paramount importance.

Successful clozapine re-challenge in a case of Atypical Neuroleptic Malignant Syndrome with markedly elevated Creatinine Phosphokinase and no muscle rigidity

Successful clozapine re-challenge in a case of Atypical Neuroleptic Malignant Syndrome with markedly elevated Creatinine Phosphokinase and no muscle rigidity

Neuroleptic malignant syndrome: evaluation of drug safety data from the AMSP program during 1993-2015.

Neuroleptic malignant syndrome (NMS) is a rare, but severe adverse drug reaction of drugs with anti-dopaminergic properties. The main symptoms are fever and rigor. In addition, other symptoms such as creatine kinase elevation, alteration of consciousness and various neurological symptoms may occur. A total of 52 NMS cases have been documented in the drug safety program 'Arzneimittelsicherheit in der Psychiatrie' from 1993 to 2015. We calculated incidences and analyzed imputed substances and additional risk factors to study the impact of changing therapy regimes. The overall incidence was 0.16‰. High-potency first-generation antipsychotics (FGAs) had the highest incidences, e.g. flupentixol with 0.61‰. Second-generation antipsychotics (SGAs) had lower incidences. Low-potency FGAs had very low incidences, comparable to SGAs, but in contrast to SGAs, had not been imputed alone in any case of NMS. Preexisting organic pathologies of the central nervous system, lithium treatment, infection/exsiccosis and the withdrawal of medication with anticholinergic properties or alcohol were found to be additional risk factors. With the increasing use of SGAs, one should always be aware of the risk of NMS. Better suited diagnostic criteria for 'atypical NMS' would lead to a better understanding and, therefore, to improved treatment possibilities.

Atypical Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) in the absence of an elevated creatine kinase is atypical and more difficult to diagnose. We present a patient with NMS significant risk factors who developed atypical NMS 6 days after a liver transplant. Symptoms of hyperthermia, altered mental status, dyskinesia, and autonomic instability (hypertension and tachycardia) coincided with promethazine administration, with rapid progression to fulminant NMS with lead pipe rigidity after a single injection of intramuscular ziprasidone. Rapid diagnosis and management resulted in full patient recovery. Differential diagnoses for NMS are discussed and a treatment algorithm is proposed.

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

Atypical neuroleptic malignant syndrome with long‐acting paliperidone

Neuroleptic malignant syndrome (NMS) is a rare but serious and potentially fatal adverse effect caused by dopamine receptor blockade associated with the use of antipsychotic agents. The incidence of NMS has been estimated to range from 0.01% to 2.4%, and the syndrome can occur in any age group, including the elderly. Classical features include mental status changes, muscular rigidity, hyperthermia, and symptoms suggestive of autonomic instability (e.g., presyncope, tachycardia, diaphoresis), with elevated creatine kinase and white blood cell count as common laboratory findings.

Atypical neuroleptic malignant syndrome in a young male precipitated by oral sodium valproate

Atypical neuroleptic malignant syndrome in a young male precipitated by oral sodium valproate

Neuroleptic Malignant Syndrome.

To review evidence for the treatment of neuroleptic malignant syndrome (NMS) and to discuss how to rechallenge patients with neuroleptics when continued pharmacotherapy for chronic psychological illness is required. A PubMed search was conducted through March 2016 using available medical subject heading (MeSH) terms and keywords that included neuroleptic malignant syndrome, treatment, dantrolene, and bromocriptine. A manual search of article reference sections followed. Case reports and case series in English that discussed NMS and atypical NMS treatment as well as neuroleptic rechallenge were included for review. The reported incidence of NMS was 0.02% to 0.03%, with a mortality rate of 5.6%. Current literature on NMS is primarily retrospective and emphasizes diagnostic criteria, causative agents, and potential pharmacotherapy. Details regarding timing of administration, dose, and duration of pharmacotherapy are inconsistently reported. Reported dosing strategies and outcomes have been summarized. Instances of rechallenge were infrequently reported but demonstrate that recurrence may happen at any time after NMS resolution. Recommendations regarding safe rechallenge are provided. NMS is a rare adverse drug reaction, with a complex pathophysiology and presentation. Timely diagnosis and discontinuation of antipsychotic therapy is the first-line treatment, followed by supportive care and pharmacotherapy. Antipsychotic rechallenge is often required and should be attempted only after a drug-free period and with a different agent, slowly titrated with close monitoring.

Atypical neuroleptic malignant syndrome in adolescence

Objective To report re-challenges of antipsychotic drugs after neuroleptic malignant syndrome (NMS) in a case of Cotard syndrome and considering electroconvulsive treatment as an option in these cases. Case report A 17-year-old adolescent, treated for acute psychotic attack with multi-antipsychotic (olanzapine, risperidone) for 15 days, developed NMS within 48hours of the addition of low doses of clozapine to his regimen. Symptoms included fever, agitation, dysautonomia, pulmonary edema, ventricular failure and laboratory findings, which included elevation of CK levels, leukocytes, transaminase, resolved after discontinuation of psychotropics, supportive management and 6 days of treatment with bromocriptine and amantadine. At first, patient was treated with low doses of quetiapine. Then, we decided to imply ECT because of two reasons. The first reason is low dosage of quetiapine was not believed to control symptoms which included Cotard syndrome based on assertions such as I am dead, I cannot breathe, My teeth and my bones are melted, suicidal thoughts, incoherence speech. The second reason is increasing quetiapine dose rapidly could have caused relapsing of NMS. Finally, we transferred our patient to another child psychiatry clinic where ECT can be applied. Discussion Starting atypical antipsychotic drugs in re-emergence of post NMS psychosis and catatonia is a challenge. Because of the risk of relapsing NMS, anti-psychotic drugs must be started lower dosage, titrated up slowly then patient should be monitored at least two weeks until resumption of therapy. Process of monitoring depends on existing of clinical residua. Moreover, it is unclear when clinical residua exist, thus it is difficult to interpret the existing guidelines on safe reintroduction of antipsychotics. At that point, ECT can be considered as an option in order to control psychotic symptoms. Conclusions Clinicians should closely monitor patients when restarting anti-psychotic drugs after NMS owing to risk of relapsing NMS and ECT should be considered as an option in order to control symptoms.

A case of clozapine intoxication presenting with atypical NMS symptoms

Clozapine is an antipsychotic drug indicated for treatment-resistant schizophrenia. Clozapine at toxic doses may cause hyperthermia, alterations in consciousness, seizures, cardiac arrhythmias, excessive mucus production in bronchi, hypersalivation, miosis, blood dyscrasias, pancreatitis and hepatitis (Sartorius et al., 2002). Clozapine blood levels are influenced by age, gender, ethnicity, physical illnesses like liver failure, changes in the activity of the cytochrome oxidase enzymes due to genetic variability, concurrent medication use, smoking or caffeine consumption (Greenwood-Smith et al., 2003). Generally, plasma levels of over 1000 ng/ml are associated with central nervous system adverse effects (Varma et al., 2011). One potentially lethal side effect of antipsychotics including clozapine is neuroleptic malignant syndrome (NMS). Neuroleptic malignant syndrome is typically characterized by fever, altered mental status, leukocytosis, autonomic dysfunction and rigidity. Atypical antipsychotics including clozapine are associated less with NMS than typical antipsychotics, and when NMS occurs during treatment with atypical antipsychotics, associated symptoms are less typical (Trollor et al., 2012). In this case report, we present a patient using clozapine for treatment of schizophrenia who was admitted to the Emergency Room with NMS-like symptoms. We present a 53 yr old, female patient diagnosed with schizophrenia, who was on clozapine 500 mg/d for the past 3 yr. She had hyperlipidemia and chronic obstructive pulmonary disease (COPD) and was using rosuvastatin 20 mg/d. She was admitted to the Emergency Room (ER) with acute onset-confusion, shivering, meaningless talk and urinary incontinence. Her body temperature was 39.2°C, blood pressure 90/50 mmHg, pulse rate 117/min, RR: 17/min, SaO2:%96. Electrocardiogram (ECG) was normal. Her Glasgow Coma Score was 15. Blood tests showed hyponatremia (133.2 mEq/l), increased levels of creatinine (1.52 mg/dl), BUN (23.68 mg/dl), uric acid (7.07 mg/dl) and decreased levels of phosphorus (2.50 mg/dl). Liver and thyroid function tests and potassium, chloride and calcium levels were within normal range. Complete …

Case Reports of Neuroleptic Malignant Syndrome in Context of Quetiapine Use

A retrospective analysis was followed on 20 case reports covering the possible correlation between the atypical antipsychotic, quetiapine, and neuroleptic malignant syndrome (NMS), determined by the study of 7 different NMS criteria guidelines. A great majority (19) of the case studies did not meet the requirements of all 7 guidelines, frequently due to unreported information. Nor was quetiapine proven to be the sole cause of the possible NMS in the two age groups investigated. Only one case was found to have no other medication or medical conditions confounding the relationship of quetiapine and NMS symptoms, and that case was in the context of a significant quetiapine overdose. The other 19 cases demonstrated the difficulty of identifying the cause of NMS when polypharmacy and other medical conditions are involved. The authors note the need for caution in deciding both the presence of NMS and the causal factors of the symptoms.

Clozapine-induced atypical neuroleptic malignant syndrome

Clozapine-induced atypical neuroleptic malignant syndrome

It’s all atypical: Can clozapine cause atypical neuroleptic malignant syndrome?

It’s all atypical: Can clozapine cause atypical neuroleptic malignant syndrome?

Atypical Neuroleptic Malignant Syndrome: Pitfalls and Challenges in the Delirious Substance Abuser

Introduction: A rare and atypical form of Neuroleptic Malignant Syndrome (NMS) can be a deceptive and life threatening condition if not diagnosed properly in acute and critical care settings. Methods: The management of a patient presenting with atypical NMS without prominent rigidity, but with extensive rhabdomyolysis after the administration of haloperidol and ziprasidone is described in this report. Results: Prompt recognition of atypical features of NMS was managed by intensive care unit admission, supportive care and pharmacotherapy, leading to a complete resolution of the syndrome and a favorable outcome verified by laboratory findings. Conclusion: Early stages and atypical features of NMS may be variable in presentation and clinical course. The absence of muscle rigidity may not rule out NMS. A strong clinical suspicion based on clinical history is crucial for early diagnosis and treatment. Termination of dantrolene therapy may not be necessary during rhabdomyolysis and elevated aminotransferase levels.

Possible Paliperidone-Induced Neuroleptic Malignant Syndrome: A Case Report

Possible Paliperidone-Induced Neuroleptic Malignant Syndrome: A Case Report

A Self-Limiting Case of Atypical Neuroleptic Malignant Syndrome Associated With Zotepine

A Self-Limiting Case of Atypical Neuroleptic Malignant Syndrome Associated With Zotepine