Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) is a life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures. Neuroleptic malignant syndrome (NMS) is a life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures. Any medications within the family of neuroleptics can cause the condition, though typical antipsychotics appear to have a higher risk than atypicals. Onset is often within a few weeks of starting the medication but can occur at any time. Risk factors include dehydration, agitation, and catatonia. Rapidly decreasing the use of levodopa may also trigger the condition. The underlying mechanism involves blockage of dopamine receptors. Diagnosis is based on symptoms. Management includes stopping the offending medication, rapid cooling, and starting other medications. Medications used include dantrolene, bromocriptine, and diazepam. The risk of death among those affected is about 10%. Rapid diagnosis and treatment is required to improve outcomes. Many people can eventually be restarted on a lower dose of antipsychotic. As of 2011, among those in psychiatric hospitals on neuroleptics about 15 per 100,000 are affected per year. In the second half of the 20th century rates were higher at about 2% (2,000 per 100,000). Males appear to be more often affected than females. The condition was first described in 1956. 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. These symptoms can last anywhere from eight hours to forty days. Symptoms are sometimes misinterpreted by doctors as symptoms of mental illness which can result in delayed treatment. 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. NMS is usually caused by antipsychotic drug use, and a wide range of drugs can result in NMS. 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. 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. In addition, other drugs with anti-dopaminergic activity, such as the antiemetic metoclopramide, can induce NMS. Even drugs without known anti-dopaminergic activity have been associated with NMS; examples include amoxapines and lithium. Also, desipramine, dothiepin, phenelzine, tetrabenazine, and reserpine have been known to trigger NMS. 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. 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 neuroleptics, a rapid increase in the dosage of neuroleptics, and use of long-acting forms of neuroleptics are all known to increase the risk of developing NMS.