Case Of 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.

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.

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.

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.

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.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

Women have been under-represented in trials of antipsychotic medications. Our primary objective was toevaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to menthrough an analysis of the FDA Adverse Event Reporting System (FAERS). We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

The role of antipsychotics and other drugs on the development and progression of neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a rare but serious and sometimes fatal complication in patients taking antipsychotic drugs, and its underlying mechanism still remains unclear. The pharmacotherapy for psychotic disorders is complicated and often involves a combination of two or more drugs, including drugs other than antipsychotics. In the present study, we used the Japanese Adverse Drug Event Report (JADER) database to broadly investigate the drugs associated with NMS, following their related pathways, as well as the drug-drug interactions (DDIs) in NMS. All analyses were performed using data from the JADER database from April 2004 to May 2022. Single-drug signals were evaluated using the reporting odds ratio (ROR) and proportional reporting ratio (PRR), and drug pathways were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG). DDIs were evaluated using the Ω shrinkage measure and Chi-square statistics models. All drugs associated with 20 or more NMS cases in the JADER database exhibited signals for NMS, including non-antipsychotics. Pathways associated with the drugs included the dopaminergic or serotonergic synapses related to antipsychotics. DDIs leading to NMS were confirmed for several drug combinations exhibiting single-drug signals. This study confirmed the significant association of various drugs, including non-psychotics, with NMS and suggested that various pathways related to these drugs may be involved in the progression of NMS. In addition, several combinations of these drugs were found to interact (DDI), increasing the risk of NMS, which suggests that appropriate caution should be taken when administering these drugs.

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.

Drug Induced Neuroleptic Malignant Syndrome: A Case Report

Neuroleptic malignant syndrome (NMS) causes fever, muscle rigidity, and impaired mental status. Drugs that influence central dopaminergic neurotransmission and almost all neuroleptics, including newer atypical antipsychotics, are also associated with it. While uncommon, NMS remains a critical differential diagnosis for patients with fever and mental status changes due to the requirement for prompt resuscitation to prevent morbidity and mortality. We present a case of a 21-year-old man with schizophrenia who attended the emergency room with generalized muscle rigidity, high-grade fever, and disturbed mental status for 12 days. His serum creatine phosphokinase was elevated (CPK). The computed tomography (CT) of the brain was normal, and the CSF was clear and cell-free. The patient was given muscle relaxants, dopamine agonists, and biperiden. After three days, rigidity, fever, and consciousness improved. A few cases of antipsychotic-induced NMS have been reported. Healthcare professionals should be aware of this fatal side effect.

Silent Neuroleptic Malignant Syndrome: A Case Report of Atypical Antipsychotic Induced Elevation of Creatinine Kinase and Altered Mental Status.

34-year-old African American male with a diagnosis of schizophrenia was placed on aripiprazole and risperidone for psychosis and mood stabilization. Two days after medication initiation, the patient's mentation was altered and he appeared confused with an elevated creatine kinase (CK) at 7101. Medications were held and CK normalized with IV fluids. Quetiapine was initiated after medical stabilization along with lithium and paliperidone palmitate injections. After the second dose of paliperidone palmitate, the patient's mentation was altered, and repeat CK was 4272. The patient received 4 liters of IV fluid and his mental status returned to baseline. There were two case studies noted that had marked increases in serum CK with risperidone use. The first was in an adolescent who was titrated to a dose of risperidone 3mg/ day but the only abnormality was an increase in his CK levels. The next case report was in a 40-year-old female who was on risperidone 2.5mg /day for one year. She had an intention tremor, minor muscle weakness of the lower extremities with a blood pressure of 140/100 and a pulse of 100. She manifested more clinical signs of possible Neuroleptic Malignant Syndrome (NMS). This case highlights the importance of laboratory investigations when there is a high suspicion of possible NMS. It also highlights that some cases of NMS may only present as altered mental status and increased CK in which quick treatment may lead to the prevention of full-blown clinical manifestations of NMS which could be life-threatening.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Antipsychotics for schizophrenia spectrum disorders with catatonic symptoms.

Neuroleptic Malignant Syndrome: Typical Antipsychotic Drugs Versus Atypical Antipsychotic Medications

Introduction: Neuroleptic malignant syndrome is an idiosyncratic reaction and a severe disorder caused by an adverse reaction to drugs with dopamine receptor- antagonist properties and is characterized by a tetrad of rigidity, fever, altered mental status, and autonomic instability. In the present assessment, typical or conventional antipsychotics have been contrasted with atypical antipsychotics with respect to recorded cases of neuroleptic malignant syndrome among a sample of nonwestern psychiatric inpatients. Methods: For assessment, all the cases with a diagnosis of neuroleptic malignant syndrome during the last sixty-two months, after exclusion of other conceivable differential diagnoses, were incorporated in the current retrospective, record-based evaluation. The clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. The valuation of independent variables was analyzed by ‘Compression of proportions. Statistical significance is defined as p value ≤0.05. Results: Amongst 19814 psychiatric inpatients, in the course of sixty-two months, eighteen cases received the diagnosis of neuroleptic malignant syndrome. As said by the findings, neuroleptic malignant syndrome was meaningfully more frequent among males, in comparison with females, and it was importantly more prevalent among cases suffering from schizophrenia, in comparison with bipolar disorder. Also, the highest risk of neuroleptic malignant syndrome was found in the age group of 30-39. In the current assessment, only one of the patients, who had received haloperidol, died due to aspiration pneumonia and respiratory failure, and the most prevalent symptom was fever, which was observable in one hundred percent of cases. In addition to a similar clinical profile, ‘Compression of proportions’ did not show any significant difference between the conventional (typical) antipsychotics versus the atypical antipsychotic medications with respect to the occurrence of neuroleptic malignant syndrome. Conclusion: As said by the findings, no significant difference was evident between the typical antipsychotic drugs versus the atypical antipsychotic medications, with respect to incidence and clinical profile of neuroleptic malignant syndrome.

Neuroleptic malignant syndrome cases in a Moroccan intensive care unit: a retrospective analysis and literature review

Background: Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening neuropsychiatric emergency. The aim of our study was to update our bedside procedures by investigating NMS cases managed in the intensive care unit (ICU).Methods: This retrospective study included all NMS patients admitted to our hospital between January 2012 and December 2019. The variables analyzed included demographics, diagnosis, therapeutics, and outcomes.Results: This study included 20 patients, with an average age of 36.6 years. The male to female ratio was 1:4. No patient had a history of NMS, and 60% of the patients had schizophrenia. First-generation neuroleptics (NLs) were the most commonly prescribed drugs (80%). The mean time between the introduction of NLs and onset of symptoms was 7.6 days. Rigidity was observed in 90% of the patients, hyperthermia and neuropsychic syndrome in 65%, and dysautonomia in 50%. The creatine phosphokinase level in all patients was four times the normal value. Mechanical ventilation was required in 20% of the patients and hemodialysis in one patient. None of the patients received specific therapy. The mean duration of ICU stay was 10 days. The mortality rate was 10%,, mainly associated with renal failure. The analysis of the predictors of mortality was limited by the size of our cohort.Conclusion: NMS is a rare condition requiring multidisciplinary implementation of contextualized and updated procedures. Early detection and supportive treatment could improve the prognosis in resource-limited settings, where specific treatments are not available. Predictive risk factors should be investigated in larger multicenter cohorts.

Symptom Frequencies and Correlations with Temperature Variations in Suspected Cases of Neuroleptic Malignant Syndrome (NMS)

Background: The incidence of NMS is rare. Relative frequencies of symptoms that are most valuable in making a diagnosis of NMS can be assessed statistically only if a large sample of suspected NMS cases is available. Similarly, the relationship of such NMS symptoms to temperature (a cardinal symptom of NMS) can be meaningfully evaluated only by studying large samples. Method: De-identified archival data on 212 suspected NMS cases were obtained from professionals across the USA and Canada or were extracted from studies published in medical journals. We recorded the symptoms frequencies. The patients’ temperature ranged from 37.20C to 43.00C, with the mean at 39.50 (SD=1.3). All cases were caused by older first-generation antipsychotics (FGAs). We evaluated the frequencies of symptoms reported in these cases. These included symptoms in the realm of mental status, rigidity, and autonomic symptoms. We calculated the frequency of abnormal blood pressure, respiration and heart rate, symptoms such as Dysarthria, Dysphagia, Rigidity, Focal Dystonia, Waxy Flexibility, Myoclonus, Masked Facies, Bradykinesia, Akinesia, Cogwheeling, Stupor, Coma, Obtundation, Mutism, Decrease in Consciousness, Disorientation, Diaphoresis, Sialorrhea, and Seizures. We also calculated their correlations with temperature elevations, the most spectacular symptom of this dangerous syndrome. Results: The highest symptom frequencies (those > 10%) were found for Rigidity (91.0% of patients), Autonomic Instability (66.5%), Diaphoresis (45.8%), Mutism (34.4%), Tremor (31.6%), Stupor (20.3%), Confusion (15.6%), Incontinence (15.6%), Sialorrhea (14.6%), Coma (13.2%), and Dysphagia (11.3%). Other symptoms were too rare within the sample of the 212 suspected NMS cases to calculate the statistical significances of their relationships to temperature. The only significant correlations found of temperature were to increased heart rate and to the severe cases of coma. Discussion and Conclusion: Besides the elevated temperature, the most frequently reported symptoms in this sample of suspected NMS caused by FGAs were Rigidity, Autonomic Instability, Diaphoresis, Mutism, and Tremor. Higher temperature was associated with tachycardia as well as profound impairment of consciousness or coma. Reviews and database studies of second generation antipsychotics (SGAs), also referred to as atypical antipsychotics, suggest a lower incidence of NMS and milder severity of symptoms such as hyperthermia and rigidity. It would be of clinical interest to generate similar de-identified files of archival data for suspected cases of NMS in patients treated with SGAs. Furthermore, a similar profile derived from archival data on milder or prodromal NMS cases could enhance our understanding of this syndrome from a spectrum perspective.

A systematic review and pooled, patient-level analysis of predictors of mortality in neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a potentially fatal, idiosyncratic reaction to antipsychotics. Due to low incidence of NMS, research on risk factors of mortality associated with NMS is limited. Two authors independently searched Medline/Embase/Cochrane/CINAHL/PsychINFO databases for case reports with author-defined NMS published in English until 05/30/2020. Demographic, clinical, treatment, and outcome data were independently extracted following PRISMA guidelines. NMS severity was rated using the Francis-Yacoub scale. Mortality risk factors were identified using a multivariable regression analysis including all characteristics that were significantly different between NMS cases resulting vs. not resulting in death. 683 cases with NMS were analyzed (median age = 36years, males = 62.1%). In a multivariable model, independent predictors of NMS mortality were lack of antipsychotic discontinuation (odds ratio (OR) = 4.39 95% confidence interval (CI) = 2.14-8.99; p < 0.0001), respiratory problems (OR = 3.54 95%CI = 1.71-7.32; p = 0.0004), severity of hyperthermia (Unit-OR = 1.30, 95%CI = 1.16-1.46; p < 0.0001), and older age (Unit-OR = 1.05, 95%CI = 1.02-1.07; p = 0.0014). Even in univariate, patient-level analyses, antipsychotic formulation was not related to death (oral antipsychotic (OAP): n = 39/554 (7.0%) vs. long-acting injectable (LAI): n = 13/129 (10.1%); p = 0.2413). Similarly, death with NMS was not related to antipsychotic class (first-generation antipsychotic: n = 38/433 (8.8%) vs. second-generation antipsychotic: n = 8/180 (4.4%); p = 0.0638). Non-antipsychotic co-treatments were not associated with NMS mortality. Despite reliance on case reports, these findings indicate that presence of respiratory alterations, severity of hyperthermia, and older age should alert clinicians to a higher NMS mortality risk, and that antipsychotics should be stopped to reduce mortality, yet when NMS arises on LAIs, mortality is not increased vs. OAPs.

Neuroleptic Malignant Syndrome Applied with Targeted Temperature Management

Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency associated with the use of dopamine receptor-antagonist properties or the rapid withdrawal of dopaminergic medications. NMS is characterized by refractory hyperpyrexia, altered mental state, dysautonomia, and rigor. If hyperpyrexia persists, it can result in multiorgan failure. Herein, we report a case of NMS occurring after metoclopramide administration in a patient with pontine hemorrhage, which was successfully treated with targeted temperature management using a surface cooling device.

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

Long-acting injectable antipsychotics (LAIs) are associated with multiple positive outcomes in psychosis, but it is unclear whether LAIs are associated with worse outcomes if neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect, occurs. We used nationwide and nationally representative databases of healthcare encounters in Finland to study the incidence and outcome predictors of NMS in patients diagnosed with schizophrenia/schizoaffective disorder between January 01, 1972 and December 31, 2017. Using a nested case-control design, we also explored differences by antipsychotic formulation (LAI vs oral antipsychotic [OAP]) and class (first-generation antipsychotic [FGA] vs second-generation antipsychotic [SGA]). One hundred seventy-two NMS cases and 1441 sex-, age-, and diagnosis-matched controls were included (age = 58.8 ± 13.1 years, males = 59.9%). Incidence of NMS was 1.99 (1.98-2.00) per 10 000 person-years. The likelihood of developing NMS did not differ by antipsychotic formulation (adjusted odds ratio [aOR]: 0.89, 95% confidence intervals [95% CI]: 0.59-1.33, for LAIs vs OAPs) or class (FGA-OAP vs SGA-OAP [aOR: 1.08, 95% CI: 0.66-1.76], FGA-LAI [aOR: 0.89, 95% CI: 0.52-1.53], SGA-LAI [aOR: 1.35, 95% CI: 0.58-3.12]). NMS risk factors included antipsychotic treatment change: increased number (odds ratios [OR]: 5.00, 95% CI: 2.56-9.73); decreased number/switch (OR: 2.43, 95% CI: 1.19-4.96); higher antipsychotic dose (>2DDDs-OR: 3.15, 95% CI: 1.61-6.18); co-treatment with anticholinergics (OR: 2.26, 95% CI: 1.57-3.24), lithium (OR: 2.16, 95% CI: 1.30-3.58), benzodiazepines (OR: 2.02, 95% CI: 1.44-3.58); and comorbid cardiovascular disease (OR: 1.73, 95% CI: 1.22-2.45). Within 30 days, 4.7% of cases with NMS died (15.1% within 1 year) without differences by antipsychotic formulation. NMS reoccurred in 5 of 119 subjects (4.2%), after a median = 795 (range = 77-839) days after rechallenge with antipsychotics. NMS remains a potentially life-threatening risk, yet these results should further contribute to mitigate concerns about LAI safety regarding NMS onset or outcomes, including mortality.

Neuroleptic malignant syndrome associated with second-generation antipsychotics (SGA): An analysis of reported cases in eudravigilance database, 2017-2020

IntroductionAntipsychotic drugs are the cornerstone of the pharmacological treatment of psychotic disorders; however, even with Second-generation antipsychotics (SGA), adverse effects continue to be extremely accentuated and the treatment effectiveness is compromised by low adherence of the patient.ObjectivesTaking into consideration the importance of adverse effects for psychotic therapeutics, this study aims to analyze the adverse effect of the Neuroleptic Malignant Syndrome (NMS) reported in EudraVigilance Database, associated with 3 widely used SGA, Risperidone, Quetiapine, and Clozapine.MethodsThe EudraVigilance Database was analyzed from 09/01/2017 to 31/10/2020 about NMS, associated with Risperidone, Quetiapine, and Clozapine. NMS is the second most reported adverse effect inside the Nervous System Disorders SOC (System Organ Class). There were just considered NMS as suspected adverse effect.ResultsIt was observed a general tendency of reduction of NMS reports from 2017 to 2020 (most of them performed by healthcare professionals). Risperidone presented the highest level of reports during this period (more than 350), followed by Quetiapine and Clozapine. The NMS reports were predominantly referred to the male sex, from 18 to 64 years old. Risperidone presented the lowest number of fatal cases of NMS (1), in contrast with 3 reported with Quetiapine and Clozapine. A significant number of patients with Schizophrenia recovered from NMS.ConclusionsIt is important to do clinical monitoring of the NMS, because it is rare, although it has life-threatening consequences. Pharmacovigilance databases are important tools to evaluate the safety of drugs and it must be more widely and efficiently promoted for healthcare and patients use.DisclosureNo significant relationships.

The neuroleptic malignant syndrome—a systematic case series analysis focusing on therapy regimes and outcome

Neuroleptic malignant syndrome (NMS) is a rare, potentially life-threatening antipsychotic-associated disorder that requires an efficient and timely therapy. The aim of the study was to compare the effectiveness of different NMS therapies and to analyze its outcome depending on NMS severity. Systematic search for NMS cases in biomedical databases. The focus of the analysis was on therapy with dantrolene, bromocriptine, and electroconvulsive therapy (ECT) when each was compared with symptomatic therapy. Primary outcomes were the survival rate and the duration of treatment. 405 case reports were included. Overall, no statistically significant differences regarding mortality rate or duration of treatment were found between dantrolene, bromocriptine, or ECT compared to supportive care. A subgroup analysis regarding NMS severity showed that the mortality under specific NMS pharmacotherapy (dantrolene, bromocriptine) and under ECT was significantly lower than under purely symptomatic therapy in severe NMS (P=0.018). The difference was not significant in mild and moderate cases. An overall superiority of the specific NMS therapy (dantrolene, bromocriptine, and ECT) was not found in this study. When regarding severity classification, specific therapies were superior but only in severe cases, and ECT showed the lowest mortality rate. In previous case series, an effect on survival or the duration of the disease could only be observed in part for specific therapies, but the evidence available is inconsistent. The results of this study support our hypothesis that NMS treatment with dantrolene, bromocriptine, and ECT is advantageous over purely symptomatic therapy in severe NMS cases.

Risk of Neuroleptic Malignant Syndrome with Vesicular Monoamine Transporter Inhibitors.

ObjectiveVesicular monoamine transporter-2 (VMAT2) inhibitors have been proven to be effective for the treatment of tardive dyskinesia and their use is likely to increase. The evidence base of published clinical reports was reviewed to evaluate the possible risk of neuroleptic malignant syndrome (NMS) with these drugs.MethodsPubmed, Embase, Web of Science and PsycINFO databases were queried for all years using terms for “neuroleptic malignant syndrome”, “hyperthermia” AND “vesicular monoamine transporter inhibitors”, “reserpine”, “tetrabenazine”, “valbenazine” or “deutetrabenazine”ResultsThirteen clinical cases, ten of which involved tetrabenazine, were identified in which VMAT2 inhibitors were prescribed in patients with current or past NMS episodes. In most cases, the association was confounded by limited reporting of clinical data, variable temporal correlation with VMAT2 inhibitors, polypharmacy with antipsychotics, and uncertain differential diagnoses.ConclusionWhile rare cases of NMS meeting consensus criteria have been reported primarily with tetrabenazine, the risk with recently developed VMAT2 inhibitors may be even less. Evidence of causality of NMS with VMAT2 inhibitors is confounded by concomitant treatment with antipsychotics and diagnostic uncertainties in patients susceptible to basal ganglia dysfunction. Nevertheless, clinicians should remain vigilant for early signs of NMS in all patients treated with any drugs that affect brain dopamine activity.