Neuroleptic malignant syndrome

Last updated
Neuroleptic malignant syndrome
Haloperidol (Haldol).jpg
Haloperidol, a known cause of NMS
Specialty Critical care medicine, neurology, psychiatry
Symptoms High fever, confusion, rigid muscles, variable blood pressure, sweating [1]
Complications Rhabdomyolysis, high blood potassium, kidney failure, seizures [1] [2]
Usual onsetWithin a few weeks or days [3]
Causes Antipsychotic medication [1]
Risk factors Dehydration, agitation, catatonia [4]
Diagnostic method Based on symptoms in someone who has started on antipsychotics within the last month [2]
Differential diagnosis Heat stroke, malignant hyperthermia, serotonin syndrome, lethal catatonia [2]
TreatmentStopping the offending medication, rapid cooling, starting other medications [2]
Medication Dantrolene, bromocriptine, diazepam [2]
Prognosis 10–15% risk of death [4]
Frequency15 per 100,000 per year (on neuroleptics) [1]

Neuroleptic malignant syndrome (NMS) is a rare [5] [6] but life-threatening reaction that can occur in response to antipsychotic (neuroleptic) medications. [1] Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. [1] Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures. [1] [2]

Contents

Any medications within the family of antipsychotics can cause the condition, though typical antipsychotics appear to have a higher risk than atypicals, [1] specifically first generation antipsychotics like haloperidol. [5] Onset is often within a few weeks of starting the medication but can occur at any time. [1] [3] Risk factors include dehydration, agitation, and catatonia. [4]

Rapidly decreasing the use of levodopa or other dopamine agonists, such as pramipexole, may also trigger the condition. [1] [7] The underlying mechanism involves blockage of dopamine receptors. [1] Diagnosis is based on symptoms. [2]

Management includes stopping the triggering medication, rapid cooling, and starting other medications. [2] Medications used include dantrolene, bromocriptine, and diazepam. [2] The risk of death among those affected is about 10%. [4] Rapid diagnosis and treatment is required to improve outcomes. [1] Many people can eventually be restarted on a lower dose of antipsychotic. [2] [3]

As of 2011, among those in psychiatric hospitals on antipsychotics about 15 per 100,000 are affected per year (0.015%). [1] In the second half of the 20th century rates were over 100 times higher at about 2% (2,000 per 100,000). [1] Males appear to be more often affected than females. [1] The condition was first described in 1956. [1]

Signs and symptoms

NMS symptoms include: [8]

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). Once symptoms appear, they may progress rapidly and reach peak intensity in as little as three days. [8] These symptoms can last anywhere from eight hours to forty days. [4]

Symptoms are sometimes misinterpreted by doctors as symptoms of mental illness which can result in delayed treatment. [10] NMS is less likely if a person has previously been stable for a period of time on antipsychotics, especially in situations where the dose has not been changed and there are no issues of noncompliance or consumption of psychoactive substances known to worsen psychosis.[ citation needed ]

Causes

NMS is usually caused by antipsychotic drug use, and a wide range of drugs can result in NMS. [11] 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. [12]

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. [13] In addition, other drugs with anti-dopaminergic activity, such as the antiemetic metoclopramide, can induce NMS. [14] 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. [15] Whether lithium can cause NMS is unclear. [16] However, concomitant use of lithium is associated with a higher risk of NMS when the patient starts on a antipsychotic drug. [17]

At the molecular level, NMS is caused by a sudden, marked reduction in dopamine activity, either from withdrawal of dopaminergic agents or from blockade of dopamine receptors. [18]

Risk factors

One of the clearest risk factors in the development of NMS is the course of drug therapy chosen to treat a condition. Use of high-potency antipsychotics, a rapid increase in the dosage of antipsychotics, and use of long-acting forms of antipsychotics (such as haloperidol) [19] are all known to increase the risk of developing NMS. [20] There appears to be no relationship between duration of therapy and the development of NMS. [6]

Use of the following agents is most commonly associated with the development of NMS: [8]

It has been purported that there is a genetic risk factor for NMS. [23] In one study, identical twins presented with NMS, and a mother and two of her daughters have presented with NMS in another case. [24]

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. [11] It has also been suggested that postpartum women may be at a greater risk for NMS. [25]

An important risk factor for this condition is Lewy body dementia. These patients are extremely sensitive to antipsychotics. As a result, antipsychotics should be used cautiously in all cases of dementia. [26]

Pathophysiology

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

It has been proposed that blockade of D2-like (D2, D3 and D4) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity. [28] [29] Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5-HT1 receptors by certain of them reduces GABA release and indirectly induces glutamate release, worsening this syndrome. [30]

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. [31]

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. [32] NMS induced by atypical drugs also resembles "classical" NMS (induced by "typical" antipsychotic drugs), further casting doubt on the overall superiority of these drugs. [33]

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. [32] This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as a mechanism for NMS. [34] 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. [4]

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. [35] 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 ]

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. [36]

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). [37] The patient may experience hypertensive crisis and metabolic acidosis. A non-generalized slowing on an EEG is reported in around 50% of cases.[ citation needed ]

The fever seen with NMS is believed to be caused by hypothalamic dopamine receptor blockade. The peripheral problems (the high white blood cell and CPK count) are caused by the antipsychotic drugs. They 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. [11]

Diagnosis

Differential diagnosis

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%. [38] Differentiating NMS from other neurological disorders can be very difficult. It requires expert judgement to separate symptoms of NMS from other diseases.

The diagnosis is suggested on patients with an accurate history of drug exposure to the most common inducing agents such as strong antidopaminergic medication. [6] [39] The differential diagnosis includes serotonin syndrome, [40] encephalitis, toxic encephalopathy, status epilepticus, heat stroke, catatonia and malignant hyperthermia. Drugs such as cocaine and amphetamine may also produce similar symptoms. [4] [41] [6] Features which distinguish NMS from serotonin syndrome include bradykinesia, muscle rigidity, and a high white blood cell count. [42]

Treatment

NMS is a medical emergency and can lead to death if untreated. The first step is to stop the antipsychotic medication and treat the hyperthermia aggressively, such as with cooling blankets or ice packs to the axillae and groin. Supportive care in an intensive care unit capable of circulatory and ventilatory support is crucial. The best pharmacological treatment is still unclear. Dantrolene has been used when needed to reduce muscle rigidity, and more recently dopamine pathway medications such as bromocriptine have shown benefit. [43] Amantadine is another treatment option due to its dopaminergic and anticholinergic effects. Apomorphine may be used however its use is supported by little evidence. [31] Benzodiazepines may be used to control agitation. Highly elevated blood myoglobin levels 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. [4]

Should the affected person subsequently require an antipsychotic, trialing a low dose of a low-potency atypical antipsychotic is recommended. [4]

Prognosis

The prognosis is best when identified early and treated aggressively. In these cases NMS is not usually fatal. In earlier studies the mortality rates from 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 improved management. [44] Re-introduction to the drug that originally caused NMS to develop may also trigger a recurrence, although in most cases it does not.[ citation needed ]

Memory impairment is a consistent feature of recovery from NMS, and is usually temporary though in some cases may become persistent. [45]

Epidemiology

Pooled data suggest the incidence of NMS is between 0.2%–3.23%. [46] However, greater physician awareness coupled with increased use of atypical anti-psychotics have likely reduced the prevalence of NMS. [11] Additionally, young males are particularly susceptible and the male:female ratio has been reported to be as high as 2:1. [11] [46] [47]

History

NMS was known about as early as 1956, shortly after the introduction of the first phenothiazines. [48] [ self-published source? ] 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. [15]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Catatonia</span> Psychiatric behavioral syndrome

Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during episodes. It has historically been related to schizophrenia, but catatonia is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions. Catatonia is now a stand-alone diagnosis, and the term is used to describe a feature of the underlying disorder.

<span class="mw-page-title-main">Serotonin syndrome</span> Symptoms caused by an excess of serotonin in the central nervous system

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders in the latter.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive compulsive disorder (OCD), tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Tardive dyskinesia</span> Neurological disorder featuring involuntary, repetitive body movements

Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be chorea or slow writhing movements. In about 20% of people with TD, the disorder interferes with daily functioning. If TD is present in the setting of a long-term drug therapy, reversibility can be determined primarily by severity of symptoms and how long symptoms have been present before the long-term drug has been stopped.

The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes the positive symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.

<span class="mw-page-title-main">Dopamine antagonist</span> Drug which blocks dopamine receptors

A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Flupentixol</span> Typical antipsychotic drug of the thioxanthene class

Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.

Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.

<span class="mw-page-title-main">Tiapride</span> Antipsychotic medication

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects.

Pleurothotonus, commonly known as Pisa syndrome, is a rare neurological disorder which occurs due to prolonged exposure to antipsychotic drugs. It is characterized by dystonia, and abnormal and sustained involuntary muscle contraction. This may cause twisting or jerking movements of the body or a body part. Although Pisa syndrome develops most commonly in those undergoing long-term treatment with antipsychotics, it has been reported less frequently in patients receiving other medications, such as an acetylcholinesterase inhibitor. However, it has also been seen in those with other diseases causing neurodegeneration and in those who are not receiving any medication. The characteristic development of Pisa syndrome consists of two types of dystonia: acute dystonia and tardive dystonia. The underlying pathology of drug-induced Pisa syndrome is very complex, and development may be due to an underlying dopaminergic-cholinergic imbalance, or serotonergic/noradrenergic dysfunction.

<span class="mw-page-title-main">Piquindone</span> Chemical compound

Piquindone (Ro 22-1319) is an atypical antipsychotic with a tricyclic structure that was developed in the 1980s but was never marketed. It acts as a selective D2 receptor antagonist, though based on its effects profile its selectivity may be considered controversial. Unlike most other D2 receptor ligands, piquindone displays Na+-dependent binding, a property it shares with tropapride, zetidoline, and metoclopramide.

<span class="mw-page-title-main">Antipsychotic switching</span> Process of transferring between antipsychotics

Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic. There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorized for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.

The dopamine hypothesis of stuttering attributes to the phenomenon of stuttering a hyperactive and disturbed dopaminergic signal transduction in the brain. The theory is derived from observations in medical neuroimaging and from the empirical response of some antipsychotics and their antagonistic effects on the dopamine receptor. However, it is important to outline that the hypothesis does not consider the excessive dopaminergic activity as the direct cause of stuttering; instead, this synaptic dysregulation is a symptom of a greater disorder that affects other brain pathways and structures.

<span class="mw-page-title-main">Bell's mania</span> Medical condition

Bell's mania, also known as delirious mania, refers to an acute neurobehavioral syndrome. This is usually characterized by an expeditious onset of delirium, mania, psychosis, followed by grandiosity, emotional lability, altered consciousness, hyperthermia, and in extreme cases, death. It is sometimes misdiagnosed as excited delirium (EXD) or catatonia due to the presence of overlapping symptoms. Pathophysiology studies reveal elevated dopamine levels in the neural circuit as the underlying mechanism. Psychostimulant users as well as individuals experiencing severe manic episodes are more prone to the manifestation of this condition. Management solutions such as sedation and ketamine injections have been discussed for medical professionals and individuals with the condition. Bell's mania cases are commonly reported in countries like the United States and Canada and are commonly associated with psychostimulant use and abuse.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Berman, Brian D. (January 2011). "Neuroleptic malignant syndrome: a review for neurohospitalists". The Neurohospitalist. 1 (1). New York City: SAGE Publications: 41–47. doi:10.1177/1941875210386491. PMC   3726098 . PMID   23983836.
  2. 1 2 3 4 5 6 7 8 9 10 "Neuroleptic Malignant Syndrome". NORD (National Organization for Rare Disorders). 2004. Archived from the original on 19 February 2017. Retrieved 1 July 2017.
  3. 1 2 3 "Neuroleptic Malignant Syndrome Information Page". Bethesda, Maryland: National Institute of Neurological Disorders and Stroke. Archived from the original on 4 July 2017. Retrieved 1 July 2017.
  4. 1 2 3 4 5 6 7 8 9 Strawn JR, Keck PE, Caroff SN (June 2007). "Neuroleptic malignant syndrome". The American Journal of Psychiatry . 164 (6): 870–876. doi:10.1176/ajp.2007.164.6.870. PMID   17541044.
  5. 1 2 New, Andrea M.; Nelson, Sarah; Leung, Jonathan G. (October 1, 2015). "Psychiatric Emergencies in the Intensive Care Unit". AACN Advanced Critical Care . 26 (4). Aliso Viejo, California: American Association of Critical-Care Nurses: 285–293. doi:10.4037/NCI.0000000000000104. PMID   26484986.
  6. 1 2 3 4 Troller, Julian N.; Chen, Xiaohua; Sachdev, Perminder S. (February 2009). "Neuroleptic malignant syndrome associated with atypical antipsychotic drugs". CNS Drugs . 23 (6). New York City: Springer Nature: 477–92. doi:10.2165/00023210-200923060-00003. PMID   19480467. S2CID   43859486.
  7. ↑ Sahin, Aynur; Cicek, Mustafa; Cekic, Ozgen Gonenc; Gunaydin, Mucahit; Aykut, Demet Saglam; Tatli, Ozgur; Karaca, Yunus; Arici, Mualla Aylin (December 2017). "A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality". Turkish Journal of Emergency Medicine. 17 (4). Ankara, Turkey: Emergency Medicine Association of Turkey: 141–145. doi:10.1016/j.tjem.2017.10.001. PMC   5812912 . PMID   29464217.
  8. 1 2 3 4 5 Simon LV, Hashmi MF, Callahan AL (August 2022). "Neuroleptic Malignant Syndrome.". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   29489248.
  9. 1 2 Papadakis MA, McPhee SJ (2023). "Neuroleptic malignant syndrome.". Quick Medical Diagnosis & Treatment. McGraw Hill.
  10. ↑ Milbouer S. "Quest for the truth". Nashua Telegraph. Archived from the original on 2007-09-27.
  11. 1 2 3 4 5 Neuroleptic Malignant Syndrome at eMedicine
  12. ↑ Khaldi S, Kornreich C, Choubani Z, Gourevitch R (December 2008). "[Neuroleptic malignant syndrome and atypical antipsychotics: a brief review]" [Neuroleptic malignant syndrome and atypical antipsychotics: A brief review]. L'Encephale (in French). 34 (6): 618–624. doi:10.1016/j.encep.2007.11.007. PMID   19081460.
  13. ↑ Keyser DL, Rodnitzky RL (April 1991). "Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy". Archives of Internal Medicine. 151 (4): 794–796. doi:10.1001/archinte.151.4.794. PMID   1672810.
  14. ↑ Friedman LS, Weinrauch LA, D'Elia JA (August 1987). "Metoclopramide-induced neuroleptic malignant syndrome". Archives of Internal Medicine. 147 (8): 1495–1497. doi:10.1001/archinte.147.8.1495. PMID   3632154.
  15. 1 2 Buckley PF, Hutchinson M (March 1995). "Neuroleptic malignant syndrome". Journal of Neurology, Neurosurgery, and Psychiatry. 58 (3): 271–273. doi:10.1136/jnnp.58.3.271. PMC   1073359 . PMID   7897404.
  16. ↑ Aronson JK (2015). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 607. ISBN   978-0-444-53716-4.
  17. ↑ Buckley PF, Hutchinson M (March 1995). "Neuroleptic malignant syndrome". Journal of Neurology, Neurosurgery, and Psychiatry. 58 (3): 271–273. doi:10.1136/jnnp.58.3.271. PMC   1073359 . PMID   7897404.
  18. ↑ "Treatment of Schizophrenia". TMedWeb: Medical Pharmacology. Tulane University. Retrieved 2021-06-19.
  19. ↑ Miller CS, Wiese JG (2017). "Hyperthermia and fever.". In McKean SC, Ross JJ, Dressler DD, Scheurer DB (eds.). Principles and Practice of Hospital Medicine (2nd ed.). McGraw Hill. ISBN   978-0-07-184313-3.
  20. ↑ Keck PE, Pope HG, Cohen BM, McElroy SL, Nierenberg AA (October 1989). "Risk factors for neuroleptic malignant syndrome. A case-control study". Archives of General Psychiatry. 46 (10): 914–918. doi:10.1001/archpsyc.1989.01810100056011. PMID   2572206.
  21. ↑ Huppert LA, Dyster TG (2021). "Key medications & interventions in psychiatry.". Huppert's Notes: Pathophysiology and Clinical Pearls for Internal Medicine. McGraw Hill. ISBN   978-1-260-47007-9.
  22. ↑ Butterworth IV JF, Mackey DC, Wasnick JD (2022). "Thermoregulation, hypothermia, & malignant hyperthermia.". Morgan & Mikhail's Clinical Anesthesiology (7th ed.). McGraw Hill. ISBN   978-1-260-47379-7.
  23. ↑ Velamoor VR (July 1998). "Neuroleptic malignant syndrome. Recognition, prevention and management". Drug Safety. 19 (1): 73–82. doi:10.2165/00002018-199819010-00006. PMID   9673859. S2CID   23303714.
  24. ↑ Otani K, Horiuchi M, Kondo T, Kaneko S, Fukushima Y (June 1991). "Is the predisposition to neuroleptic malignant syndrome genetically transmitted?". The British Journal of Psychiatry. 158 (6): 850–853. doi:10.1192/bjp.158.6.850. PMID   1678666. S2CID   23185221.
  25. ↑ Alexander PJ, Thomas RM, Das A (May 1998). "Is risk of neuroleptic malignant syndrome increased in the postpartum period?". The Journal of Clinical Psychiatry. 59 (5): 254–255. doi: 10.4088/JCP.v59n0509a . PMID   9632037.
  26. ↑ Steinberg M, Lyketsos CG (September 2012). "Atypical antipsychotic use in patients with dementia: managing safety concerns". The American Journal of Psychiatry. 169 (9): 900–906. doi:10.1176/appi.ajp.2012.12030342. PMC   3516138 . PMID   22952071.
  27. ↑ Mihara K, Kondo T, Suzuki A, Yasui-Furukori N, Ono S, Sano A, et al. (February 2003). "Relationship between functional dopamine D2 and D3 receptors gene polymorphisms and neuroleptic malignant syndrome". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 117B (1): 57–60. doi:10.1002/ajmg.b.10025. PMID   12555236. S2CID   44866985.
  28. ↑ Kornhuber J, Weller M, Riederer P (1993). "Glutamate receptor antagonists for neuroleptic malignant syndrome and akinetic hyperthermic parkinsonian crisis". Journal of Neural Transmission. Parkinson's Disease and Dementia Section. 6 (1): 63–72. doi:10.1007/bf02252624. PMID   8105799. S2CID   45530847.
  29. ↑ Chatterjee A (January 2014). "Glutamate-based magnetic resonance spectroscopy in neuroleptic malignant syndrome". Annals of Indian Academy of Neurology. 17 (1): 123–124. doi: 10.4103/0972-2327.128579 . PMC   3992752 . PMID   24753679.
  30. ↑ Odagaki Y (January 2009). "Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics?". Current Drug Safety. 4 (1): 84–93. CiteSeerX   10.1.1.334.241 . doi:10.2174/157488609787354387. PMID   19149529.
  31. 1 2 Wijdicks EF (26 May 2022). Aminoff MJ, Rabinstein AA, Wilterdink JL (eds.). "Neuroleptic malignant syndrome". UpToDate.
  32. 1 2 Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T (April 2004). "Neuroleptic malignant syndrome and atypical antipsychotic drugs". The Journal of Clinical Psychiatry. 65 (4): 464–470. doi:10.4088/JCP.v65n0403. PMID   15119907. S2CID   32752143.
  33. ↑ Hasan S, Buckley P (August 1998). "Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique". The American Journal of Psychiatry. 155 (8): 1113–1116. doi:10.1176/ajp.155.8.1113. PMID   9699705.
  34. ↑ Gurrera RJ (February 1999). "Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome". The American Journal of Psychiatry. 156 (2): 169–180. doi:10.1176/ajp.156.2.169. PMID   9989551. S2CID   31276121.
  35. ↑ Gurrera RJ (2002). "Is neuroleptic malignant syndrome a neurogenic form of malignant hyperthermia?". Clinical Neuropharmacology. 25 (4): 183–193. doi:10.1097/00002826-200207000-00001. PMID   12151905. S2CID   29010904.
  36. ↑ Northoff G (December 2002). "Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology". Journal of Neural Transmission. 109 (12): 1453–1467. CiteSeerX   10.1.1.464.9266 . doi:10.1007/s00702-002-0762-z. PMID   12486486. S2CID   12971112.
  37. ↑ Latham J, Campbell D, Nichols W, Mott T (August 2008). "Clinical inquiries. How much can exercise raise creatine kinase level--and does it matter?". The Journal of Family Practice. 57 (8): 545–547. PMID   18687233. Archived from the original on 2016-06-01.
  38. ↑ Stringer JL, ed. (2017). "Antipsychotics or neuroleptics.". Basic Concepts in Pharmacology: What You Need to Know for Each Drug Class (5th ed.). McGraw Hill. ISBN   978-1-259-86107-9.
  39. ↑ Yandle G, deBoisblanc BP (2014). "Persistent fever". In Hall JB, Schmidt GA, Kress JP (eds.). Principles of Critical Care (4th ed.). McGraw Hill. ISBN   978-0-07-173881-1.
  40. ↑ Christensen V, Glenthøj BY (January 2001). "[Malignant neuroleptic syndrome or serotonergic syndrome]". Ugeskrift for Laeger. 163 (3): 301–302. PMID   11219110.
  41. ↑ Sachdev PS (June 2005). "A rating scale for neuroleptic malignant syndrome". Psychiatry Research. 135 (3): 249–256. doi:10.1016/j.psychres.2005.05.003. PMID   15996751. S2CID   25728796.
  42. ↑ Birmes P, Coppin D, Schmitt L, Lauque D (May 2003). "Serotonin syndrome: a brief review". CMAJ. 168 (11): 1439–1442. PMC   155963 . PMID   12771076.
  43. ↑ Dhib-Jalbut S, Hesselbrock R, Mouradian MM, Means ED (February 1987). "Bromocriptine treatment of neuroleptic malignant syndrome". The Journal of Clinical Psychiatry. 48 (2): 69–73. PMID   3804991.
  44. ↑ Ahuja N, Cole AJ (2009). "Hyperthermia syndromes in psychiatry". Advances in Psychiatric Treatment. 15 (3): 181–91. doi: 10.1192/apt.bp.107.005090 .
  45. ↑ Mendhekar DN, Duggal HS (2006). "Persistent amnesia as a sequel of olanzapine-induced neuroleptic malignant syndrome". The Journal of Neuropsychiatry and Clinical Neurosciences. 18 (4): 552–553. doi: 10.1176/jnp.2006.18.4.552 . PMID   17135384.
  46. 1 2 Pelonero AL, Levenson JL, Pandurangi AK (September 1998). "Neuroleptic malignant syndrome: a review". Psychiatric Services. 49 (9): 1163–1172. doi:10.1176/ps.49.9.1163. PMID   9735957.
  47. ↑ Hernández JL, Palacios-Araus L, Echevarría S, Herrán A, Campo JF, Riancho JA (December 1997). "Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome". Postgraduate Medical Journal. 73 (866): 779–784. doi:10.1136/pgmj.73.866.779. PMC   2431511 . PMID   9497946.
  48. ↑ Friedberg JM. "Neuroleptic malignant syndrome". Archived from the original on October 16, 2006. Retrieved 2006-07-03.[ self-published source ]
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.