Neuroleptic malignant syndrome

NMS symptoms include:{{cite book | vauthors = Simon LV, Hashmi MF, Callahan AL | chapter = Neuroleptic Malignant Syndrome. | date = August 2022 | title = StatPearls [Internet]. | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 29489248 | url = https://www.ncbi.nlm.nih.gov/books/NBK482282/ }}

• Increased body temperature >38 °C (>100.4 °F)
• Confused or altered consciousness
• Excessive sweating{{cite book | chapter = Neuroleptic malignant syndrome. | vauthors = Papadakis MA, McPhee SJ | date = 2023 | title = Quick Medical Diagnosis & Treatment | publisher = McGraw Hill | url = https://accessmedicine.mhmedical.com/content.aspx?bookid=3241§ionid=271755113 }}
• Severely rigid muscles
• Autonomic imbalance

The first symptoms of neuroleptic malignant syndrome are usually muscle cramps and tremors, fever, symptoms of autonomic nervous system instability such as unstable blood pressure, and sudden changes in mental status (agitation, delirium, or coma). Other possible symptoms include sweating, trouble swallowing, tremors, incontinence, and mutism. Once symptoms appear, they may progress rapidly and reach peak intensity in as little as three days. These symptoms can last anywhere from eight hours to forty days, with the median duration of symptoms, with treatment, being nine days.{{cite journal |last1=Wijdicks |first1=Eelco F.M. |last2=Ropper |first2=Allan H. |title=Neuroleptic Malignant Syndrome |journal=New England Journal of Medicine |date=26 September 2024 |volume=391 |issue=12 |pages=1130–1138 |doi=10.1056/NEJMra2404606|pmid=39321364 }} The median onset of symptoms is four days after initiating the offending medication, but in some cases symptoms may begin up to 30 days later.

Symptoms are sometimes misinterpreted by doctors as symptoms of mental illness which can result in delayed treatment.{{cite web | vauthors = Milbouer S | title = Quest for the truth | work = Nashua Telegraph | url = http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=/20050424/NEWS01/104240081 | archive-url = https://web.archive.org/web/20070927222612/http://www.nashuatelegraph.com/apps/pbcs.dll/article?AID=%2F20050424%2FNEWS01%2F104240081 |archive-date=2007-09-27 }} Symptoms may also be mistaken for similarly presenting conditions such as malignant hyperthermia, serotonin syndrome, or withdrawal from illicit drugs such as alcohol, cocaine, or MDMA.

Neuroleptic malignant syndrome (NMS) usually presents with a "lead pipe rigidity" in which the muscles are stiffened and resistance is observed throughout the range of motion on testing. Severe cases may present as catatonia in which the person is not responsive to stimuli.

The deep tendon reflexes in NMS are usually preserved whereas serotonin syndrome presents with myoclonus or hyperactive muscle reflexes.

NMS is usually caused by antipsychotic drug use, but other dopaminergic blocking drugs can also be a cause.{{Emedicine|article|816018|Neuroleptic Malignant Syndrome}} Individuals using butyrophenones (such as haloperidol and droperidol) or phenothiazines (such as promethazine and chlorpromazine) are reported to be at greatest risk. However, various atypical antipsychotics such as clozapine, olanzapine, risperidone, quetiapine, and ziprasidone have also been implicated in cases.{{cite journal | vauthors = Khaldi S, Kornreich C, Choubani Z, Gourevitch R | title = [Neuroleptic malignant syndrome and atypical antipsychotics: a brief review] | language = fr | journal = L'Encephale | volume = 34 | issue = 6 | pages = 618–624 | date = December 2008 | pmid = 19081460 | doi = 10.1016/j.encep.2007.11.007 | trans-title = Neuroleptic malignant syndrome and atypical antipsychotics: A brief review }}

NMS may also occur in people taking dopaminergic drugs (such as levodopa) for Parkinson's disease, most often when the drug dosage is abruptly reduced.{{cite journal | vauthors = Keyser DL, Rodnitzky RL | title = Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy | journal = Archives of Internal Medicine | volume = 151 | issue = 4 | pages = 794–796 | date = April 1991 | pmid = 1672810 | doi = 10.1001/archinte.151.4.794 }} In addition, other drugs with anti-dopaminergic activity, such as the antiemetic metoclopramide, can induce NMS.{{cite journal | vauthors = Friedman LS, Weinrauch LA, D'Elia JA | title = Metoclopramide-induced neuroleptic malignant syndrome | journal = Archives of Internal Medicine | volume = 147 | issue = 8 | pages = 1495–1497 | date = August 1987 | pmid = 3632154 | doi = 10.1001/archinte.147.8.1495 }} Tetracyclics with anti-dopaminergic activity have been linked to NMS in case reports, such as the amoxapines. Additionally, desipramine, dothiepin, phenelzine, tetrabenazine, and reserpine have been known to trigger NMS.{{cite journal | vauthors = Buckley PF, Hutchinson M | title = Neuroleptic malignant syndrome | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 58 | issue = 3 | pages = 271–273 | date = March 1995 | pmid = 7897404 | pmc = 1073359 | doi = 10.1136/jnnp.58.3.271 }} Whether lithium can cause NMS is unclear.{{cite book | vauthors = Aronson JK |title=Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions |date=2015 |publisher=Elsevier |isbn=978-0-444-53716-4 |page=607 |url=https://books.google.com/books?id=NOKoBAAAQBAJ&pg=RA3-PA607 |language=en}} However, concomitant use of lithium is associated with a higher risk of NMS when a person starts on an antipsychotic drug.{{cite journal | vauthors = Buckley PF, Hutchinson M | title = Neuroleptic malignant syndrome | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 58 | issue = 3 | pages = 271–273 | date = March 1995 | pmid = 7897404 | pmc = 1073359 | doi = 10.1136/jnnp.58.3.271 }}

At the molecular level, NMS is caused by a sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agents or blockade of dopamine receptors.{{Cite web|title= Treatment of Schizophrenia | work = TMedWeb: Medical Pharmacology | publisher = Tulane University |url=https://tmedweb.tulane.edu/pharmwiki/doku.php/rx_of_schizophrenia|access-date=2021-06-19 |language=en}}

The use of antipsychotics as well as how this class of medications is used is one of the most common risk factors for NMS. Use of high-potency antipsychotics, a rapid increase in the dosage of antipsychotics, use of long-acting forms of antipsychotics (such as haloperidol) or injectable formulations, or using multiple antipsychotics are all known to increase the risk of developing NMS.{{cite book | vauthors = Miller CS, Wiese JG | date = 2017 | chapter = Hyperthermia and fever. | veditors = McKean SC, Ross JJ, Dressler DD, Scheurer DB | title = Principles and Practice of Hospital Medicine | edition = 2nd | publisher = McGraw Hill | url = https://accessmedicine.mhmedical.com/content.aspx?bookid=1872§ionid=146976769 | isbn = 978-0-07-184313-3 }}{{cite journal | vauthors = Keck PE, Pope HG, Cohen BM, McElroy SL, Nierenberg AA | title = Risk factors for neuroleptic malignant syndrome. A case-control study | journal = Archives of General Psychiatry | volume = 46 | issue = 10 | pages = 914–918 | date = October 1989 | pmid = 2572206 | doi = 10.1001/archpsyc.1989.01810100056011 }} Dehydration is a risk factor for the development of NMS. There appears to be no relationship between duration of therapy and the development of NMS.

Use of the following agents is most commonly associated with the development of NMS:

• Typical antipsychotics: e.g. haloperidol, chlorpromazine.{{cite book | chapter = Key medications & interventions in psychiatry. | vauthors = Huppert LA, Dyster TG | date = 2021 | title = Huppert's Notes: Pathophysiology and Clinical Pearls for Internal Medicine. | publisher = McGraw Hill | chapter-url = https://accessmedicine.mhmedical.com/content.aspx?bookid=3072§ionid=257403886 | isbn = 978-1-260-47007-9 }}
• Anti-dopaminergic antiemetics: e.g. droperidol
• Withdrawal of dopaminergic agents: e.g. levodopa, amantadine{{cite book | chapter = Thermoregulation, hypothermia, & malignant hyperthermia. | vauthors = Butterworth IV JF, Mackey DC, Wasnick JD | date = 2022 | title = Morgan & Mikhail's Clinical Anesthesiology | edition = 7th | publisher = McGraw Hill | url = https://accessmedicine.mhmedical.com/content.aspx?bookid=3194§ionid=266525430 | isbn = 978-1-260-47379-7 }}

It has been purported that there is a genetic risk factor for NMS.{{cite journal | vauthors = Velamoor VR | title = Neuroleptic malignant syndrome. Recognition, prevention and management | journal = Drug Safety | volume = 19 | issue = 1 | pages = 73–82 | date = July 1998 | pmid = 9673859 | doi = 10.2165/00002018-199819010-00006 | s2cid = 23303714 }} In one study, identical twins presented with NMS, and a mother and two of her daughters have presented with NMS in another case.{{cite journal | vauthors = Otani K, Horiuchi M, Kondo T, Kaneko S, Fukushima Y | title = Is the predisposition to neuroleptic malignant syndrome genetically transmitted? | journal = The British Journal of Psychiatry | volume = 158 | issue = 6 | pages = 850–853 | date = June 1991 | pmid = 1678666 | doi = 10.1192/bjp.158.6.850 | s2cid = 23185221 }}

Demographically, it appears that males, especially those under forty, are at greatest risk for developing NMS, although it is unclear if the increased incidence is a result of greater antipsychotic use in men under forty. It has also been suggested that postpartum women may be at a greater risk for NMS.{{cite journal | vauthors = Alexander PJ, Thomas RM, Das A | title = Is risk of neuroleptic malignant syndrome increased in the postpartum period? | journal = The Journal of Clinical Psychiatry | volume = 59 | issue = 5 | pages = 254–255 | date = May 1998 | pmid = 9632037 | doi = 10.4088/JCP.v59n0509a | doi-access = free }}

Antipsychotic use in those with Lewy body dementia is a risk factor for NMS. These people are extremely sensitive to antipsychotics. As a result, antipsychotics should be used cautiously in all cases of dementia.{{cite journal | vauthors = Steinberg M, Lyketsos CG | title = Atypical antipsychotic use in patients with dementia: managing safety concerns | journal = The American Journal of Psychiatry | volume = 169 | issue = 9 | pages = 900–906 | date = September 2012 | pmid = 22952071 | pmc = 3516138 | doi = 10.1176/appi.ajp.2012.12030342 }}

The mechanism is commonly thought to depend on decreased levels of dopamine activity due to:

• Dopamine receptor blockade
• Genetically reduced function of dopamine receptor D₂{{cite journal | vauthors = Mihara K, Kondo T, Suzuki A, Yasui-Furukori N, Ono S, Sano A, Koshiro K, Otani K, Kaneko S | display-authors = 6 | title = Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 117B | issue = 1 | pages = 57–60 | date = February 2003 | pmid = 12555236 | doi = 10.1002/ajmg.b.10025 | s2cid = 44866985 }}
• Sympathoadrenal hyperactivity and autonomic dysfunction

It has been proposed that blockade of D₂-like (D₂, D₃ and D₄) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity.{{cite journal | vauthors = Kornhuber J, Weller M, Riederer P | title = Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic parkinsonian crisis | journal = Journal of Neural Transmission. Parkinson's Disease and Dementia Section | volume = 6 | issue = 1 | pages = 63–72 | year = 1993 | pmid = 8105799 | doi = 10.1007/bf02252624 | s2cid = 45530847 }}{{cite journal | vauthors = Chatterjee A | title = Glutamate-based magnetic resonance spectroscopy in neuroleptic malignant syndrome | journal = Annals of Indian Academy of Neurology | volume = 17 | issue = 1 | pages = 123–124 | date = January 2014 | pmid = 24753679 | pmc = 3992752 | doi = 10.4103/0972-2327.128579 | doi-access = free }} Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5-HT₁ receptors by some may reduce GABA release and indirectly induce glutamate release, worsening this proposed glutamatergic neurotoxicity.{{cite journal | vauthors = Odagaki Y | title = Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics? | journal = Current Drug Safety | volume = 4 | issue = 1 | pages = 84–93 | date = January 2009 | pmid = 19149529 | doi = 10.2174/157488609787354387 | citeseerx = 10.1.1.334.241 }}

The muscular symptoms are most likely caused by blockade of the dopamine receptor D₂, leading to abnormal function of the basal ganglia similar to that seen in Parkinson's disease.{{Cite web | vauthors = Wijdicks EF | date = 26 May 2022 | veditors = Aminoff MJ, Rabinstein AA, Wilterdink JL |url= https://www.uptodate.com/contents/neuroleptic-malignant-syndrome|title=Neuroleptic malignant syndrome | work = UpToDate }}

In the past, research and clinical studies seemed to corroborate the D₂ receptor blockade theory in which antipsychotic drugs were thought to significantly reduce dopamine activity by blocking the D₂ receptors associated with this neurotransmitter. The introduction of atypical antipsychotic drugs, with lower affinity to the D₂ dopamine receptors, was thought to have reduced the incidence of NMS. However, recent studies suggest that the decrease in mortality may be the result of increased physician awareness and earlier initiation of treatment rather than the action of the drugs themselves. NMS induced by atypical drugs also resembles "classical" NMS (induced by "typical" antipsychotic drugs), further casting doubt on the overall superiority of these drugs.{{cite journal | vauthors = Hasan S, Buckley P | title = Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique | journal = The American Journal of Psychiatry | volume = 155 | issue = 8 | pages = 1113–1116 | date = August 1998 | pmid = 9699705 | doi = 10.1176/ajp.155.8.1113 }}

However, the failure of D₂ dopamine receptor antagonism, or dopamine receptor dysfunction, do not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D₂ dopamine activity.{{cite journal | vauthors = Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T | title = Neuroleptic malignant syndrome and atypical antipsychotic drugs | journal = The Journal of Clinical Psychiatry | volume = 65 | issue = 4 | pages = 464–470 | date = April 2004 | pmid = 15119907 | doi = 10.4088/JCP.v65n0403 | s2cid = 32752143 }} This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as a mechanism for NMS.{{cite journal | vauthors = Gurrera RJ | title = Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome | journal = The American Journal of Psychiatry | volume = 156 | issue = 2 | pages = 169–180 | date = February 1999 | pmid = 9989551 | doi = 10.1176/ajp.156.2.169 | s2cid = 31276121 }} Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in the breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical antipsychotics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.

In support of the sympathoadrenal hyperactivity model, it has been hypothesized that a defect in calcium regulatory proteins within the sympathetic neurons may bring about the onset of NMS.{{cite journal | vauthors = Gurrera RJ | title = Is neuroleptic malignant syndrome a neurogenic form of malignant hyperthermia? | journal = Clinical Neuropharmacology | volume = 25 | issue = 4 | pages = 183–193 | year = 2002 | pmid = 12151905 | doi = 10.1097/00002826-200207000-00001 | s2cid = 29010904 }} This model of NMS strengthens its suspected association with malignant hyperthermia in which NMS may be regarded as a neurogenic form of this condition which itself is linked to defective calcium-related proteins.{{citation needed|date=December 2020}}

There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.{{cite journal | vauthors = Northoff G | title = Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology | journal = Journal of Neural Transmission | volume = 109 | issue = 12 | pages = 1453–1467 | date = December 2002 | pmid = 12486486 | doi = 10.1007/s00702-002-0762-z | s2cid = 12971112 | citeseerx = 10.1.1.464.9266 }}

The raised white blood cell count and creatine phosphokinase (CPK) plasma concentration seen in those with NMS is due to increased muscular activity and rhabdomyolysis (destruction of muscle tissue).{{cite journal | vauthors = Latham J, Campbell D, Nichols W, Mott T | title = Clinical inquiries. How much can exercise raise creatine kinase level--and does it matter? | journal = The Journal of Family Practice | volume = 57 | issue = 8 | pages = 545–547 | date = August 2008 | pmid = 18687233 | url = http://www.jfponline.com/home/article/how-much-can-exercise-raise-creatine-kinase-level-and-does-it-matter/86f4f4fd65053888a3d529aca00eb455.html | url-status = live | archive-url = https://web.archive.org/web/20160601202531/http://www.jfponline.com/home/article/how-much-can-exercise-raise-creatine-kinase-level-and-does-it-matter/86f4f4fd65053888a3d529aca00eb455.html | archive-date = 2016-06-01 }} Someone may experience hypertensive crisis and metabolic acidosis.

The fever seen with NMS is believed to be caused by hypothalamic dopamine receptor blockade. Antipsychotics cause an increased calcium release from the sarcoplasmic reticulum of muscle cells which can result in rigidity and eventual cell breakdown. No major studies have reported an explanation for the abnormal EEG, but it is likely also attributable to dopamine blockage leading to changes in neuronal pathways.

Due to the comparative rarity of NMS, it is often overlooked. Immediate treatment for the syndrome should not be delayed as it has a high mortality of between 10-20%.{{cite book | chapter = Antipsychotics or neuroleptics. | veditors = Stringer JL | date = 2017 | title = Basic Concepts in Pharmacology: What You Need to Know for Each Drug Class | edition = 5th | publisher = McGraw Hill | chapter-url = https://accessmedicine.mhmedical.com/content.aspx?bookid=2147§ionid=161351718 | isbn = 978-1-259-86107-9 }} Differentiating NMS from other neurological disorders can be very difficult.

The diagnosis is suggested on patients with a history of drug exposure to the most common inducing agents such as strong antidopaminergic medications.{{cite book | vauthors = Yandle G, deBoisblanc BP | date = 2014 | chapter = Persistent fever | veditors = Hall JB, Schmidt GA, Kress JP | title = Principles of Critical Care | edition = 4th | publisher = McGraw Hill | chapter-url = https://accessmedicine.mhmedical.com/content.aspx?bookid=1340§ionid=80033832 | isbn = 978-0-07-173881-1 }} The differential diagnosis includes serotonin syndrome,{{cite journal | vauthors = Christensen V, Glenthøj BY | title = [Malignant neuroleptic syndrome or serotonergic syndrome] | journal = Ugeskrift for Laeger | volume = 163 | issue = 3 | pages = 301–302 | date = January 2001 | pmid = 11219110 }} encephalitis, toxic encephalopathy, status epilepticus, heat stroke, catatonia and malignant hyperthermia. Drugs such as cocaine and amphetamine may also produce similar symptoms.{{cite journal | vauthors = Sachdev PS | title = A rating scale for neuroleptic malignant syndrome | journal = Psychiatry Research | volume = 135 | issue = 3 | pages = 249–256 | date = June 2005 | pmid = 15996751 | doi = 10.1016/j.psychres.2005.05.003 | s2cid = 25728796 | hdl = 1959.4/unsworks_46263 | hdl-access = free }} Features which distinguish NMS from serotonin syndrome include bradykinesia, muscle rigidity, and a high white blood cell count.{{cite journal | vauthors = Birmes P, Coppin D, Schmitt L, Lauque D | title = Serotonin syndrome: a brief review | journal = CMAJ | volume = 168 | issue = 11 | pages = 1439–1442 | date = May 2003 | pmid = 12771076 | pmc = 155963 | url = http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=12771076 }}

NMS is a medical emergency and can lead to death if untreated. The first step is to stop the culprit medication and treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Acetaminophen is commonly used as an anti-pyretic. Supportive care in an intensive care unit capable of circulatory and ventilatory support is crucial. In those unable to control their secretions, or who have muscle spams of the respiratory muscles, mechanical ventilation may be needed.

The best pharmacological treatment is still unclear. Dantrolene has been used when needed to reduce muscle rigidity, and dopamine pathway medications such as bromocriptine have shown benefit.{{cite journal | vauthors = Dhib-Jalbut S, Hesselbrock R, Mouradian MM, Means ED | title = Bromocriptine treatment of neuroleptic malignant syndrome | journal = The Journal of Clinical Psychiatry | volume = 48 | issue = 2 | pages = 69–73 | date = February 1987 | pmid = 3804991 }} Dantrolene may act centrally on thermoregulatory pathways to lower the temperature. Dantrolene also inhibits calcium release from the muscle sarcoplasmic reticulum to cause muscle relaxation.

Amantadine is another treatment option due to its dopaminergic and anticholinergic effects.

Apomorphine may be used however its use is supported by little evidence. Benzodiazepines may be used to control agitation. Highly elevated blood myoglobin levels from muscle breakdown (rhabdomyolysis) can result in kidney damage, therefore aggressive intravenous hydration with diuresis may be required. When recognized early NMS can be successfully managed; however, up to 10% of cases can be fatal.

Should the affected person subsequently require an antipsychotic, trialing a low dose of a low-potency atypical antipsychotic is recommended.

Electroconvulsive therapy may be used in life threatening cases of NMS that are refractory to first line treatments.

The prognosis is best when identified early and treated aggressively. In earlier studies the mortality rates of NMS ranged from 20%–38%, but by 2009 mortality rates were reported to have fallen below 10% over the previous two decades due to early recognition and improvements in management.{{cite journal | vauthors = Ahuja N, Cole AJ |title=Hyperthermia syndromes in psychiatry |journal=Advances in Psychiatric Treatment |volume=15 |issue=3 |year=2009 |pages=181–91 |doi=10.1192/apt.bp.107.005090|doi-access=free }} Re-introduction of antipsychotics after NMS may trigger a recurrence, although in most cases it does not. With recurrence rate being 4.2% in a small, population based study.{{cite journal |last1=Guinart |first1=Daniel |last2=Taipale |first2=Heidi |last3=Rubio |first3=Jose M |last4=Tanskanen |first4=Antti |last5=Correll |first5=Christoph U |last6=Tiihonen |first6=Jari |last7=Kane |first7=John M |title=Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort |journal=Schizophrenia Bulletin |date=21 October 2021 |volume=47 |issue=6 |pages=1621–1630 |doi=10.1093/schbul/sbab062|pmid=34013325 |pmc=8530388 }}

Pooled data suggest the incidence of NMS is between 0.2%–3.23%.{{cite journal | vauthors = Pelonero AL, Levenson JL, Pandurangi AK | title = Neuroleptic malignant syndrome: a review | journal = Psychiatric Services | volume = 49 | issue = 9 | pages = 1163–1172 | date = September 1998 | pmid = 9735957 | doi = 10.1176/ps.49.9.1163 }} However, greater awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS. Additionally, young males are particularly susceptible and the male to female ratio has been reported to be as high as 2:1.{{cite journal | vauthors = Hernández JL, Palacios-Araus L, Echevarría S, Herrán A, Campo JF, Riancho JA | title = Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome | journal = Postgraduate Medical Journal | volume = 73 | issue = 866 | pages = 779–784 | date = December 1997 | pmid = 9497946 | pmc = 2431511 | doi = 10.1136/pgmj.73.866.779 }}

NMS was known about as early as 1956, shortly after the introduction of the first phenothiazines.{{cite web | vauthors = Friedberg JM | title = Neuroleptic malignant syndrome | url=http://www.idiom.com/~drjohn/biblio.html |access-date=2006-07-03 |url-status=dead |archive-url=https://web.archive.org/web/20061016043024/http://www.idiom.com/~drjohn/biblio.html |archive-date=October 16, 2006 }} {{self-published source|date=April 2016}}{{self-published inline|date=April 2016}} NMS was first described in 1960 by French clinicians who had been working on a study involving haloperidol. They characterized the condition that was associated with the side effects of haloperidol "syndrome malin des neuroleptiques", which was translated to neuroleptic malignant syndrome.

{{Reflist}}

• [https://www.ninds.nih.gov/Disorders/All-Disorders/Neuroleptic-Malignant-Syndrome-Information-Page NINDS Neuroleptic Malignant Syndrome Information Page]—NIH.

{{Medical resources

| DiseasesDB = 8968

| ICD10 = {{ICD10|G|21|0|g|20}}

| ICD9 = {{ICD9|333.92}}

| eMedicineSubj = emerg

| eMedicineTopic = 339

| eMedicine_mult = {{eMedicine2|med|2614}}{{eMedicine2|ped|1581}}

| MeshID = D009459

}}

{{Diseases of the nervous system}}

{{DEFAULTSORT:Neuroleptic Malignant Syndrome}}

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Category:Extrapyramidal and movement disorders

Category:Medical emergencies

Category:Rare syndromes

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