Incidence Of Neuroleptic Malignant Syndrome Research Articles

Antipsychotic-associated neuroleptic malignant syndrome (NMS) in schizophrenia patients: a narrative review

Neuroleptic malignant syndrome (NMS) is a neurological disorder with an high mortality rate among schizophrenia patients who receive antipsychotics as the primary long-term therapy. Appropriate selection of antipsychotics in NMS should be carefully considered to obtain maximal effectiveness with minimal side effects. An evaluation of the safety profile of the antipsychotics is important due to their different treatment patterns and rapid onset of symptoms. This review article aimed to compare the safety profile of antipsychotics in relation to NMS in schizophrenia patients. It was a narrative review using multiple search engines included PubMed, Google Scholar, and Springer to collect publications from 2007 to 2023. Of the total 14 articles reviewed, 7 articles explained the role of antipsychotics in NMS, 5 articles about the onset of NMS, and 7 articles about mortality rate. The incidence of NMS was less then 0.11%, typical antipsychotics were the most common cause of NMS, especially high-potency antipsychotics compared with atypical antipsychotics. Meanwhile, the onset of NMS consistently occured within 30 d of antipsychotic initiation with a symptom duration of 1 to 30 d, and the mortality rate was also higher for typical antipsychotics. In conclusion, the choice of antipsychotics must be carefully considered and its use must be monitored due to the rapid onset and high mortality. The use of antipsychotics is not free from the risk of NMS. The heterogeneous symptoms of NMS require earlier detection to reduce disease progression.

Analysis of the Serie of Cases of Neuroleptic Malignant Syndrome (Cross-Sectional Observational Study)

Background: neuroleptic malignant syndrome (NMS) is the most dangerous complication of therapy with neuroleptics with high mortality. The publications on MNS are the reviews articles or case reports.The aim of study: an identification of the frequency of occurrence of NMS harm in patients of the city psychiatric hospital over a 4-year period, a clarification of the clinical manifestations of this complication, an analysis of the effectiveness of the treatment and rate of deaths.Patients and methods: 19 cases with a confirmed diagnosis of NMS who were treated for 4 years in one of the clinical psychiatric hospitals in Moscow with 1158 beds. All patients met the criteria for the diagnosis of NMS according to DSM-5 (333.92). The severity of extrapyramidal disorders was assessed on the Simpson–Angus Rating Scale (SAS). The Bush–Francis Catatonia Rating Scale (BFCRS) was used to assess the features and severity of catatonic symptoms. All patients underwent a study of the general clinical analysis and biochemical analysis of blood with the determination of the number of leukocytes and the activity of the enzyme creatine phosphokinase (CPK).Results: the incidence of NMS was 0.035% of all treated patients, mortality— 10.5%. Most often, NMS develops during treatment with haloperidol and much less frequently with the appointment of atypical antipsychotics risperidone and clozapine in patients with schizophrenia, acute polymorphic mental disorder, organic mental disorders, including dementia. The influence of such factors as gender, age, type of disease on the development of NMS has not been established. The age of patients with a fatal outcome was higher than the average for the group. The clinical picture of NMS was characterized by a combination of catatonic, extrapyramidal and somato-vegetative disorders with hyperthermia, leukocytosis and increased activity of CPK.Conclusion: today NMS remains a relatively rare, but extremely dangerous complication of antipsychotic therapy, with a high risk of death and can develop both in the treatment with first and second generation antipsychotics in patients with schizophrenia and acute polymorphic mental disorder and in organic mental disorders, including dementia.

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.

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.

A case of aripiprazole-Induced neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a serious medical emergency with significant fatality rates if not recognized and treated early. High-potency first-generation antipsychotics are reported to have more incidence of NMS. Aripiprazole-induced NMS is very rare, and here we report the case of a 38-year-old woman with bipolar illness disorder. The disorder started after escalating the dose and resolved after stopping the medicine.

Re-Challenge with Clozapine after Neuroleptic Malignant Syndrome and Seizure in a Patient with Di-George Syndrome: Case Report and Review of Literature

Background: Individuals with 22q11.2DS, a genetic subtype of Schizophrenia, respond as well to clozapine as those with other forms of Schizophrenia. It has been reported that serious and rare adverse events like seizures, and myocarditis have been associated with clozapine treatment in this population. To the best of our knowledge, the incidence of neuroleptic malignant syndrome (NMS) as an adverse effect of antipsychotic use in patients with this disorder has not yet been reported. Aim: In this article, we discuss a case of clozapine-induced NMS and subsequent re-challenge in a patient with 22q11.2DS-associated schizophrenia. The aim of this study is to accumulate scientific data about rare presentations, and serve as a major educational tool, and highlight the unique challenges faced when using clozapine in a patient with DiGeorge Syndrome. Methods: This is a descriptive case report of a patient encountered in the inpatient unit which includes retrospective review of the patient’s electronic medical record and a literature review of antipsychotic medications-induced NMS. Conclusion: This study demonstrates a successful re-challenge with clozapine after the patient developed NMS and seizures during the initial treatment and also highlights how, in addition to drug level monitoring, considering pharmacogenetic testing early in treatment might help minimize adverse drug reactions in individuals with known genetic disorders such as 22q11.2DS.

Fluvoxamine-induced neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is an uncommon but life-threatening idiosyncratic drug reaction that occurs following neuroleptic drug exposure. The estimated incidence of NMS is though very low, resulting mortality rates range between 4% and 30%. There is increasing evidence that “Atypical” antipsychotics are associated with NMS that has a different character. NMS occurring with selective serotonin reuptake inhibitors' use is extremely rare, and it should be differentiated from serotonin syndrome. Here, we report a rare case of NMS induced by fluvoxamine.

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.

Akinetic crisis in dementia with Lewy bodies

Background and purposeDementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or...

Life-threatening conditions in psychiatry – neuroleptic malignant syndrome (NMS)

The introduction of neuroleptics in the 1950’s was a turning point in psychiatric treatment. The new drugs brought hope to millions of patients and their doctors. However, there were also some side-effects, one of which is Neuroleptic malignant syndrome (NMS), a rare complication of antipsychotic treatment and untreated it may lead to mortality as high as 20%. The incidence of NMS, estimated to be 0.01–0.02%, has decreased significantly probably due to higher awareness of the diseases and shift to atypical antipsychotics. The aim of this study was to present the signs and symptoms of this rare condition and describe management possibilities since this condition is observed not only in psychiatric departments but also in emergency rooms. NMS is thought to be related to change caused by neuroleptics within the central nervous system due to dopamine D2 receptor antagonism, especially nigrostriatal pathways and the hypothalamus. There are three symptoms which are considered as major and indicate a high probability of NMS: muscle rigidity, hyperthermia (core body temperature above 38.5 °C), and elevated creatine phosphokinase concentration (above 1000 U/l). NMS is a diagnosis of exclusion and clinicians must be vigilant in detecting early signs of NMS. The basic management in NMS is antipsychotic discontinuation and proper supportive care of the patient (vital signs monitoring, hydration, correction of electrolyte and acid-base disturbances). In more severe cases, the introduction of bromocriptine or dantrolene, as well as benzodiazepines, may indicated. Further usage of neuroleptic in patients with a history of NMS should be with care, and low doses of low-potency neuroleptics or atypical neuroleptics seem to be the best treatment choice.

EPA-0362 – Neuroleptic malignant syndrome – an atypical presentation with quetiapine

Neuroleptic malignant syndrome (NMS) is a life-threatening condition associated with the use of neuroleptic drugs and is characterized by a clinical syndrome of mental status change, muscle rigidity, fever, and autonomic instability. The incidence of NMS seems to has been decreasing, possibly due to increased awareness, changes in drug prescribing practices, the use of lower doses of dopamine blocking agents and atypical antipsychotics. The risk factors most consistently identified with precipitating NMS are prominent psychomotor agitation and incrementally higher doses of one or more parenterally administered neuroleptics. The use of atypical antipsychotics may be associated with: a decreased risk, decreased mortality, and atypical features of NMS. To alert clinicians for atypical presentations of NM. To report and discuss, based on online pubmed database, a case of a NMS with no muscle rigidity, in spite of an extremely elevated CK level, due to quetiapine. Atypical cases of NMS without muscle rigidity and/or hyperthermia have been reported in database. With the widespread use of atypical antipsychotics, atypical presentations of NMS should be more frequent. While not yet proven, it has been hypothesized that such atypical cases are a prodrome of the disease and represent impending NMS with typical presentation. Clinicians must be aware for this atypical presentation of the NSM since adherence to strict diagnostic criteria may lead to alternate and/or delayed diagnosis, with eventually poor outcomes. For this reason, a strong clinical suspicion based on clinical history is crucial for early diagnosis and treatment.

Neuroleptic Malignant Syndrome Revisited in the Perspective of Pakistan

Abstract Objective: Neuroleptic malignant syndrome (NMS) is a life threatening adverse reaction of antipsychotic drugs, especially of dopamine receptor antagonists (DRA's). In addition to clinical and pharmacological risk factors, legal and ethical risk factors may be con-tributory towards the incidence, diagnosis and prog-nosis of NMS in Pakistan. Study Design: Experimental case study. Place and Duration of Study: The department of psychiatry and behavioral sciences of Bahawal Vic-toria Hospital affiliated with Quaid-e-Azam Medical College, from July 2011 to October 2012. Subjects and Methods: All the patients with proba-ble NMS, received consecutively at the inpatient depa-rtment of psychiatry, were included and investigated to rule out any other medical condition mimicking the syndrome. The patients were treated till complete recovery from the syndrome. The psychiatric diagno-ses were confirmed, during their hospital stay, accord-ing to ICD 10 Diagnostic Criteria for Research, the residual symptoms were recorded and tabulated along with other important characteristics of the patients. Results: Reckless use of DRA's in the form of intra-muscular depot injections or high initial oral doses, along with certain other previously perceived clinical risk factors, increased the chance of developing NMS. Female gender and younger age along with early dete-ction and prudent management proved to be good pro-gnostic factors for NMS in our study. The diverse categories of the first hand attending health providers e.g. doctors, quacks and faith healers of our psychiatric patients frequently used antipsychotics. This scenario points towards the lapses in determination of pathways to care, legality and ethics governing the mental health care in Pakistan. Conclusion: Standard protocol must be followed to start antipsychotics in psychotic patients, especially while planning to use depot DRA's. The manic pati-ents are even more sensitive to develop extrapyramidal side effects and neuroleptic malignant syndrome; these patients can better be managed with zuclopinthixol acetate (colpixol acuphase) injections when oral medi-cation is not feasible. These drugs should not be used in neurotic patients. The introduction of depot injec-tions of serotonin and dopamine antagonists (SDA's) may minimize the incidence of NMS. In Pakistan, a task force should immediately be constituted to inclu-de Mental Health Ordinance (MHO) 2001 into the constitution so that the serious legal and ethical issues of the mental health care are solved, accordingly. Key Words: Neuroleptic Malignant Syndrome (NMS), risk factors, adverse reaction, antipsychotics.

Neuroleptic malignant syndrome controversies revisited—what is the incidence of neuroleptic malignant syndrome?

Neuroleptic malignant syndrome controversies revisited—what <i>is</i> the incidence of neuroleptic malignant syndrome?

Coexistence of neuroleptic malignant syndrome and a hyperosmolar hyperglycemic state

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic disorder characterized by muscle rigidity, hyperthermia, autonomic dysfunction, and altered consciousness. Although the incidence of NMS is low, it may be fatal if early recognition is delayed. There are a variety of precipitating factors for NMS including systemic illness and dehydration. The combination of NMS with systemic illness can be difficult to diagnose because the systemic illness may mask the coexistence of NMS. We report a patient with hyperosmolar hyperglycemic state with coexistent NMS to remind physicians that hyperosmolar hyperglycemic state may precipitate the development of NMS in patients receiving neuroleptics.

Catatonia: Clinical Aspects and Neurobiological Correlates

Catatonia is a neuropsychiatric syndrome that can occur due to medical or psychiatric disorder. This review synthesizes over 20 years of original research and comprehensive review articles with attention to the most recent findings. Though catatonia is common and highly treatable, there have been few research studies investigating the syndrome. Pooled case reports suggest that catatonia due to an underlying general medical condition and catatonia due to a psychiatric illness can be treated similarly and that the catatonic symptoms and the underlying illness must be addressed in both types. Benzodiazepines and ECT continue to be mainstays of treatment. Evidence is mounting for the use of NMDA antagonists in catatonia refractory to lorazepam.

Amisulpride-Induced Neuroleptic Malignant Syndrome

Back to table of contents Previous article Next article LETTERFull AccessAmisulpride-Induced Neuroleptic Malignant SyndromeErcan Abay M.D.,Rugul Kose M.D.,Ercan Abay M.D.Search for more papers by this author,Rugul Kose M.D.Search for more papers by this author,Published Online:1 Oct 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal complication of antipsychotic medication. The risk of developing NMS under atypical neuroleptics seems lower than under typicals. The use of atypical neuroleptics is increasing, so the incidence of NMS under these drugs may also increase. Case Report“Mr. K” was a 73-year-old man with a 5-year history of DSM-IV-TR bipolar disorder and no history of NMS. He had benign prostate hipertrophy and coronary atrery disease and was using medication for these diseases, too.His medication had been changed from olanzapine to amisulpride. On the fourth day of his treatment, he developed clouding of conciousness and admitted to emergency service. He was stuporous, had increased muscle tone, diaphoresis, elevated body temperature (38.4°C), elevated blood pressure (140/100) and metabolic disturbance. First CK (creatinine kinase) value was found to be 1798 U/liter (49–397 U/liter).Neuroleptic malignant syndrome was our diagnosis. Amisulpride was stopped immediately, fluid replacement and bromocriptine were started. Consciousness level improved immediately, metabolic status returned to normal within few days and CK levels decreased. No depressive and manic symptoms were seen and his treatment was arranged accordingly.This case is diagnosed according to DSM-IV-TR criteria. The diagnosis is supported by the rapid improvement in the consciousness level and resolution of metabolic disturbance with discontinuation of amisulpride. We saw similar cases in our service, approximately one case every 2–3 months. Sometimes there is atypical presentation with DSM-IV diagnostic criteria not met but always following a change in antipsychotic medication.Fever, muscle rigidity, and autonomic instability can be caused by neuroleptics in the absence of NMS. Catatonia has also been reported with neuroleptic use. Therefore maybe it is better to consider a dimensional approach and consider NMS in the spectrum concept. Presentation of syndrome with different drugs is different and it can be seen as a result of some antidepressants, lithium, dopamine-depleting drugs and cessation of dopaminergic drugs. We found two demonstrated cases with the use of amisulpiride. We want to report the case in order for us to collect data for upcoming classification of NMS risk by symptomatology, antipsychotic dosage and patient profile. This will allow clinicians to determine the possibility of NMS before even prescribing the drug.Department of Psychiatry, Trakya University School of Medicine, Edirne, TurkeyDepartment of Psychiatry, Trakya University School of Medicine, Edirne, Turkey FiguresReferencesCited byDetailsCited ByLa Presse Médicale, Vol. 47, No. 2Drugs in R&D, Vol. 15, No. 1 Volume 19Issue 4 Fall, 2007Pages 488-489 Metrics PDF download History Published online 1 October 2007 Published in print 1 October 2007

The neuroleptic malignant syndrome: A report of 14 cases from North India

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening but potentially treatable condition. This study was performed to investigate the clinical spectrum, antecedent events and outcome of NMS patients admitted in the Neurology department of a large teaching hospital of North India. Fourteen cases of NMS were taken after a thorough search during a three-year period (May 2000 to April 2003). The Incidence of NMS was 1.40/ 1000 patients treated with neuroleptics and mortality rate was 14.28%. Amongst the neuroleptics Haloperidol (parenteral) was implicated as a most common drug for NMS in 57% of patients. An association with coexisting precipitating illness was clearly recorded in 71.4% patients. All the recorded patients of NMS received 500-700 mg CPZ equivalent/day of neuroleptics. NMS as an indiosyncratic phenomenon was noticed in 28% patients. 85.7% responded to dopaminergic drugs along with supportive treatment and showed partial or complete recovery within 7-14 days. In those with partial recovery residual deficits included Parkinsonian features, depression and diaphoresis in a small percentage of patients.

A case of neuroleptic malignant syndrome induced by olanzapine in postpartum period

Neuroleptic malignant syndrome (NMS) is a life-threatening medical complication that occurs as a result of dopaminergic receptor blockage in nigrostriatal pathways. This syndrome is mainly accepted to be an idiosyncratic reaction for antipsychotic medications. Incidence of NMS induced by olanzapine - an atypical antipsychotic - is extremely rare. However, there has been contradiction on postpartum period as a risk factor for NMS. This case is of interest due to the fact that it happens on postpartum period and is induced by olanzapine. We aimed in this study to evaluate the successfully cured case of neuroleptic malignant syndrome induced by olanzapine in postpartum period with the literature view.

Neuroleptic Malignant Syndrome Caused by Risperidone Overdose: A case report

Neuroleptic malignant syndrome (NMS) is a rare, but potentially fatal idiosyncratic reaction to neuroleptics characterized by muscle rigidity, fever, altered consciousness, autonomic instability, leukocytosis and elevated creatinine phosphokinase level suggesting muscle injury. The incidence of NMS is estimated to be between 0.07 and 2.2% among patients receiving neuroleptics, with a motality of 11%. Although the pathophysiology of NMS is not completely understood, reduced dopaminergic activity secondary to antipsychotic induced dopamine receptor blockage is considered to be the best explanation to date. We experienced NMS in a 22-year-old male with antipsychotic drug intoxication who underwent primary closure of dual, self-inflicted wrist laceration. We recognized as NMS about 30 minutes after induction of general anesthesia. All anesthetics were stopped, and supportive care was performed with management of hyperthermia and fluid. Also, Dantrolene sodium and bromocriptine were administered. The patient recovered without any complication.

Neuroleptic Malignant Syndrome: No Longer Exclusively a “Neuroleptic” Phenomenon

Objective: To review the literature concerning the incidence of neuroleptic malignant syndrome (NMS) associated with the use of atypical antipsychotics. Data Sources: Cases were identified through a search of MEDLINE (1986–March 2004) using the terms neuroleptic malignant syndrome, antipsychotic, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Study Selection and Data Extraction: Case reports of possible NMS secondary to second-generation antipsychotics were selected for review. Reports meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for NMS were considered. Case reports in which 1 of the 2 major diagnostic criteria was met were also included in the analysis. Furthermore, at least one minor criterion was met. Case reports in which patients received traditional antipsychotics were excluded. Data Synthesis: NMS is a rare and sometimes fatal disease. Several theories exist as to how NMS develops, and an equally large amount of diagnostic criteria are available. However, the majority of available data are based on the first-generation neuroleptics and very few exist with regard to the second-generation antipsychotics. Conclusions: Although there are numerous case reports of NMS occurring secondary to the use of second-generation antipsychotics, the incidence has never been fully elucidated. While the reasons for this remain uncertain, not all cases of second-generation–induced NMS fulfill the diagnostic criteria established for traditional neuroleptics and therefore may not be reported as such.