A recent review of NMS treatments reported only 14 guidelines thematically related to its management, 8 of which were in English, 6 in German and 1 in French (Schnfeldt-Lecuona Reference Schnfeldt-Lecuona, Cronemeyer and Hiesener2020). Severe hyperthermia is treated aggressively, mainly with physical cooling (see Heatstroke: Treatment Treatment Heatstroke is hyperthermia accompanied by a systemic inflammatory response causing multiple organ dysfunction that may result in death. Indeed, following antipsychotic discontinuation, patients recover within an average of 7 to 10 days. Laboratory evaluation is essential to exclude other causes of hyperthermia (mainly infections, metabolic and endocrine abnormalities, as well as drug-induced syndromes) and to detect medical complications of NMS. Diagnosis Treatment Key Points Neuroleptic malignant syndrome is characterized by altered mental status, muscle rigidity, hyperthermia, and autonomic hyperactivity that occur when certain neuroleptic drugs are used. } Use OR to account for alternate terms Although most people who experience NMS never have another episode, some people may, especially if proper precautions are not followed. Furthermore, it remains unknown why patients who develop NMS are usually able to continue being treated with similar medications and, at times, even the same offending agent (Khaldi Reference Khaldi, Kornreich and Choubani2008; Berman Reference Berman2011). The syndrome was first characterized in the 1960s, soon after the introduction of the first antipsychotic drugs. Neuroleptic malignant syndrome. This might be due to several factors, including a probable increase in the overall (and especially off-label) use of antipsychotics (Procyshyn Reference Procyshyn, Su and Elbe2014), increased pharmacovigilance (Tse Reference Tse, Barr and Scarapicchia2015) and several systematic biases in the published studies (Gurrera Reference Gurrera, Simpson and Tsuang2007). This article discusses the clinical presentation of the syndrome, its differential diagnosis and use of supportive care, medication and electroconvulsive therapy in its treatment. Learn about the condition so you know how best to be aware of it. Neuroleptic malignant syndrome (NMS) is a relatively rare but potentially fatal complication of the use of neuroleptic drugs. Serotonin syndrome is described as a clinical triad of mental status changes, autonomic hyperactivity and neuromuscular changes. Please confirm that you are not located inside the Russian Federation. The abrupt change in stimulation to dopamine receptors seems to dysregulate the autonomic nervous system (part of your body that regulates many unconscious bodily functions). Bromocriptine must be administered orally or through a nasogastric tube as there is no parenteral preparation available. It is also debated whether the potency and dose of the rechallenge drug are an independent predictor of recurrence. A disruption of numerous. A delay of at least 2 weeks in restarting antipsychotic treatment is advised following full resolution of NMS. JMdeclares that he has no competing interests. Several types of medications can cause NMS, but antipsychotics are the most common instigators. Typically, blood pressure elevation in NMS is defined as systolic or diastolic increase 25% above baseline. It is indeed likely that the risk of recurrence is more linked to the wash-out period than to the actual antipsychotic agent that is reintroduced (Pileggi Reference Pileggi and Cook2016). NMS of moderate severity requires ICU care, and use of benzodiazepines and/or bromocriptine has been shown to be effective in improving clinical response compared with supportive care alone (Rosenberg Reference Rosenberg and Green1989). Motor abnormalities: Patients may have generalized, severe muscle rigidity (sometimes with simultaneous tremor, leading to cogwheel rigidity) or, less often, dystonias, chorea, or other abnormalities. ECT is known to reduce mortality in NMS compared with supportive care alone (Davis Reference Davis, Janicak and Sakkas1991). This includes drugs with weak dopamine-blocking properties such as promethazine, which has been incriminated in cases of NMS and should be immediately withdrawn if NMS is suspected (Chandran Reference Chandran, Mikler and Keegan2003; Velamoor Reference Velamoor2017). NMS was originally described with first-generation (conventional or typical) antipsychotics. The diagnosis of NMS is sometimes difficult, as it can resemble other conditions. Supportive care is the mainstay of treatment for NMS and it should occur in a setting where blood pressure, cardiac rhythm and pulse oximetry can be continuously monitored. Key Summary NMS is a rare but potentially fatal adverse reaction, most commonly seen with antipsychotic agents SGAs may have a lower incidence of NMS than FGAs Combinations of antipsychotics or antipsychotics with lithium or antidepressants may increase the risk of NMS It causes a high fever and muscle stiffness. It is characterised by hyperthermia, muscle rigidity, altered mental status, sympathetic nervous system lability, and hypermetabolism, as well as elevated creatine kinase. Possible pharmacological factors include high dosages and/or parenteral administration of causative agents. Dantrolene 0.25 to 2 mg/kg IV every 6 to 12 hours to a maximum of 10 mg/kg/24 hours can be given for hyperthermia. These include neurological and medical conditions, substance- or medication-induced syndromes, as well as psychiatric conditions. A starting dose of 2.5mg administered 23 times daily, to be increased by 2.5mg every 24h until a response is obtained or until a maximum dose of 45mg/day is reached can be used. Use to remove results with certain terms Response is noted within minutes of administration. pheochromocytoma, thyrotoxicosis, tetanus, heat stroke) (Velamoor Reference Velamoor2017; Ware Reference Ware, Feller and Hall2018). These drugs are commonly prescribed for the treatment of schizophrenia and other neurological, mental, or emotional disorders. BOX 1 Royal College of Psychiatrists and Royal College of Physicians statement on neuroleptic malignant syndrome. Neuroleptic malignant syndrome is a life-threatening reaction that may occur as a result of taking certain antipsychotic medicines. [1] General symptomatic treatment, such as hydration, nutrition and reduction of fever, is essential. Nonetheless, all psychiatrists practising without immediate on-site supervision should be able to diagnose NMS. Therefore, a thorough review of the case by obtaining an accurate symptom and medication history (especially any temporal relationship), physical examination and laboratory investigations can help in diagnosis and further management (Velamoor Reference Velamoor2017; Rowland Reference Rowland, Banga and Ayadurai2018; Ware Reference Ware, Feller and Hall2018). The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Hence, it is important to rule out other diagnoses that may present similarly (Table 1). Medication-related factors include antipsychotic polypharmacy, high-potency or high-dose antipsychotics, adjunctive psychotropic medications (e.g. Drugs such as levodopa can be given to help increase dopamine stimulation. The most commonly observed abnormality is elevated creatine kinase. This topic covers the diagnosis and management of neuroleptic malignant syndrome in adults. The classic presentation is that of hyperpyrexia, muscle rigidity, mental state changes and autonomic instability. However, in most cases, if the offending agent is discontinued, NMS is self-limited. "useRatesEcommerce": true Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal adverse reaction to drugs. TAO declares that she has no competing interests. The differential diagnoses listed here are not exhaustive. 2014;5:47. doi:10.3389/fpsyt.2014.00047, Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Use to remove results with certain terms Adjunctive drug therapy can be used, although efficacy has not been shown in clinical trials. Patients of all ages can be affected. Yet, apart from possibly blonanserin and perospirone, SGAs appear to be significantly less associated with NMS than haloperidol, with clozapine being possibly the safest in this regard, followed by quetiapine (Anzai Reference Anzai, Takahashi and Watanabe2019). Standard therapeutic doses of antipsychotics or other dopamine receptor antagonists can cause NMS. Neurological or medical conditions that need to be ruled out include central nervous system infections, inflammatory or autoimmune conditions, status epilepticus, subcortical structural lesions and systemic conditions (e.g. In contrast, NMS is often slower in onset and usually takes 914 days to remit in spite of appropriate treatment. NMS is a medical emergency. In a study including 1346 in-patients from a US nationwide sample for the years 20022011, the NMS mortality rate was 5.6%, with a trend of decreased mortality over the years (Modi Reference Modi, Dharaiya and Schultz2016). BOX 3 Reinstating antipsychotic treatment after neuroleptic malignant syndrome (NMS): checklist, Recheck the accuracy of the diagnosis of the NMS episode, Document indications for antipsychotic medications, Consider alternative pharmacological agents, Discuss risks and benefits, including the risk of recurrence, with patient and family, Monitor vital signs and neurological status. Obtain as needed to rule out differential diagnoses of NMS. When rechallenging after NMS, it is generally advised that a different antipsychotic is used, although one case series found that recurrence rates were similar regardless of whether the same or a different antipsychotic was used (Wells Reference Wells, Sommi and Crismon1988). Our website is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Common differential diagnoses are sepsis and drug reactions. Source: adapted from Schnfeldt-Lecuona et al (Reference Schnfeldt-Lecuona, Cronemeyer and Hiesener2020) and van Rensburg & Decloedt (Reference van Rensburg and Decloedt2019). Berman BD. Management includes discontinuation of the culprit medication, supportive measures, and, in some cases, pharmacotherapy (e.g, dantrolene, bromocriptine, lorazepam). It can occur at any time during antipsychotic therapy, but the risk is highest immediately after starting the medication or following a dose increase. and Serotonin syndrome is an important differential diagnosis, but it is hard to differentiate from NMS when it comes to clinical presentation owing to overlap of symptoms. Other drug-induced syndromes, like serotonin syndrome, also must be eliminated as possibilities. Diagnosis is clinical. However, the diagnosis of NMS remains clinical, since strict use of the criteria might make clinicians miss atypical (less severe) forms of NMS (Tse Reference Tse, Barr and Scarapicchia2015). . However, central thermoregulation is mediated by noradrenergic, serotonergic and cholinergic pathways, as well as the dopaminergic pathways, and it is therefore unlikely that NMS is due to central dopamine blockade alone. Clinically read more ). NMS may be more difficult to diagnose in someone without these classic symptoms. All approved the final draft. No eLetters have been published for this article. Neuroleptic malignant syndrome is a rare but very serious potential syndrome that can result from certain medicationsparticularly certain psychiatric medications. Most commonly, NMS occurs after a person is given a drug that blocks dopamine receptors. While NMS is a diagnosis of exclusion, laboratory studies to support the diagnosis may show elevated creatine kinase (CPK), myoglobinuria, leukocytosis, and metabolic acidosis. Some potentially helpful tests might include: Fortunately, due to greater awareness of the condition, people tend to be diagnosed more quickly than they were in the past. NMS is more likely to occur after sudden changes in these drugs. Ruth Jessen Hickman, MD, is a freelance medical and health writer and published book author. Dantrolene is recommended for severe forms of NMS, administered alone or together with benzodiazepines and bromocriptine. Serotonin syndrome is an adverse reaction caused by therapeutic drug use, intentional overdose or drug interactions leading to excessive stimulation of serotonergic receptors in the peripheral and central nervous system. BMJ Best Practice would like to gratefully acknowledge the previous expert contributor, whose work has been retained in parts of the content: Disclosures: RJG is a member of the Neuroleptic Malignant Syndrome Professional Advisory Board, and has given expert testimony in medical malpractice tort claims in which NMS was alleged. 2023. Reflex responses tend to be decreased. Early manifestations can be missed because mental status changes may be overlooked or dismissed in patients with psychosis. [4], Coadministration of dantrolene and calcium channel blockers can cause cardiovascular collapse. In patients who had developed NMS on clozapine, the outcome of clozapine rechallenge was favourable in 92% of cases, with no death reported even in the unfavourable outcome group who had an NMS recurrence (Lally Reference Lally, Mccaffrey and O'Murchu2019). Liaison psychiatry services within acute hospitals can manage the mental health needs of such patients, so these needs should never influence the decision to transfer.. Psychiatric differential diagnoses are primarily represented by malignant catatonia associated with mood or psychotic illness (Sethi Reference Sethi2004). There is substantial variation in clinical presentation of NMS, ranging from mild to life-threatening. Overall mortality rates that were reported in the 1970s and 1980s were high: 27.7% before 1980, dropping to 22.6% between 1980 and 1983, and then to 11.6% between 1984 and 1987 (Shalev Reference Shalev, Hermesh and Munitz1989). All contributed to the drafting and critical review and to the revision following peer review. Rapid cooling, control of agitation, and other aggressive supportive measures. As discussed, symptoms of NMS sometimes return if treatment is discontinued before complete clearance of the offending medication. Low-dose heparin seems to be indicated to prevent venous thrombosis in an immobilised patient. Verywell Health's content is for informational and educational purposes only. For example, certain drugs to prevent vomiting (such as metoclopramide) also block certain dopamine receptors. It is mainly associated with antipsychotic drugs, originally known as neuroleptic drugs. Prompt discontinuation of antipsychotics is essential with any suspicion of NMS. Serial measurements of white blood cell count and creatine kinase are also warranted. NMS has also been associated with other agents that block central dopamine pathways (e.g., metoclopramide). hasContentIssue false, Clinical features of neuroleptic malignant syndrome, Prevention of neuroleptic malignant syndrome, Antipsychotic rechallenge following neuroleptic malignant syndrome. Discontinue suspected causative agent (e.g., Tse L, Barr A, Scarapicchia V, Vila-Rodriguez F, Evidence-based content, created and peer-reviewed by physicians. 2023 Dotdash Media, Inc. All rights reserved, Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. , resulting in movement disorders and impaired, The clinical presentation of NMS is heterogenous and varies widely; e.g., fulminant symptoms that develop over hours, and. Learn more about the Merck Manuals and our commitment to Global Medical Knowledge. Similar syndromes resulting from the use of other substances or medications include serotonin syndrome, Parkinsonian hyperthermia syndrome following abrupt discontinuation of dopamine agonists, alcohol or sedative withdrawal, malignant hyperthermia occurring during anaesthesia, hyperthermia associated with misuse of stimulants and hallucinogens, as well as atropine poisoning from anticholinergics. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening complication of treatment with antipsychotic drugs, or abrupt withdrawal of dopamine agonists. Serotonin syndrome can cause symptoms quite similar to NMS. We use cookies to distinguish you from other users and to provide you with a better experience on our websites. aripiprazole) (Agrawal Reference Agrawal, Bajaj and Bajaj2019). FALTER: Fever, Autonomic instability, Leukocytosis, Tremor, Elevated enzymes (creatine kinase, transaminases), and Rigidity are common findings in neuroleptic malignant syndrome. The link you have selected will take you to a third-party website. It is recommended that bromocriptine to be continued for 10 days after symptoms are controlled and then tapered slowly to minimise the likelihood of recurrence of NMS (Bhanushali Reference Bhanushali and Tuite2004; Strawn Reference Strawn, Keck and Caroff2007). metoclopramide, prochlorperazine) can also induce NMS (American Psychiatric Association 2013). Serotonin vs. Dopamine: What Are the Differences? Early recognition remains paramount to avoid complications and death, with careful monitoring of vital signs and mental state. Long-acting drugs and high-dose drugs may also be more likely to trigger NMS. This has reduced long-term problems and death rate from the syndrome. Dont stop taking medications without first consulting with your treatment teamthat might lead to other major problems. Or you might be able to use a lower dose of the drug you are taking, lowering the risk of NMS. There are no published randomised controlled trials on the management of NMS, and there are no treatments specifically approved for NMS. In other words, NMS has its greatest potential risk when increasing the dose of a dopamine-blocking drug (like haloperidol) or decreasing the dose of a dopamine-stimulating drug. This improvement in NMS outcome is probably due to better recognition of the syndrome, early intervention and the availability of intensive supportive care (Modi Reference Modi, Dharaiya and Schultz2016). It is characterised by hyperthermia, muscle rigidity, altered mental status, sympathetic nervous system lability, and hypermetabolism, as well as elevated creatine kinase. Furthermore, low serum iron is a potential risk factor for NMS . If the NMS was instead triggered by stopping a dopamine-stimulating drug (like for Parkinsons disease), the drugs should be restarted. Antiemetics (Anti-Nausea Drugs) for the Treatment of Migraine. With the common use of SGAs nowadays, it is possible that such presentations are becoming more and more common. Neuroleptic malignant syndrome is rare idiosyncratic reaction to antipsychotics, which is associated with substantially high morbidity and mortality. Systemic infections, including sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. Neuroleptic malignant syndrome. Other medical risk factors include catatonia, organic brain syndrome or previous brain injury, Parkinson's disease, hyperthyroidism, alcoholism, use of restraints, iron deficiency, exhaustion, dehydration and agitation (Berman Reference Berman2011; Stroup Reference Stroup and Gray2018). Generally speaking, one needs to wait at least a couple of weeks before resuming treatment. Benzodiazepines, bromocriptine (a centrally acting dopamine agonist), amantadine (a dopamine agonist) and dantrolene (a muscle relaxant) can be used. The most commonly used diagnostic criteria are the DSM-5 criteria (American Psychiatric Association 2013) and Levenson's criteria (Levenson Reference Levenson1985). Clinically, neuroleptic malignant syndrome resembles. Other observed findings include: elevations in catecholamines, lactate dehydrogenase and aspartate transaminase; leucocytosis; low serum iron levels; metabolic acidosis; and hypoxia (Velamoor Reference Velamoor2017; Ware Reference Ware, Feller and Hall2018).