NMS is a rare but serious possible side effect of antipsychotic medication. The causes are not completely known but are thought to be related to dopamine blockade in specific areas in the brain. NMS is more common with first generation antipsychotics but it can happen with the second generation ones (see this post on the difference between first and second generation) and it has also been seen with antiemetic drugs (drugs that treat nausea) that have anti-dopamine effects in the brain.
Symptoms
There are four main symptoms of NMS and in almost all patients all four symptoms are present and develop over 1-3 days.
Mental status change.
Muscular rigidity.
Hyperthermia.
Autonomic instability.
Cases can be atypical and not all symptoms develop at the same time. I would always consider a diagnosis of NMS in a patient on antipsychotics if 2 of these 4 symptoms are present in a patient and then I would probably order some blood tests, escpecially CK (see below).
Blood tests
Elevated creatine kinase (CK). CK is found in muscles and increases if muscles break down which happens in NMS, probably due to the muscle rigidity. More muscle rigidity leads to a higher CK in blood test and a higher CK is related to a more severe NMS and a worse prognosis.
Other blood tests are not specific for NMS but we can see high white blood cells, a mild elevation of liver function tests, abnormal electrolytes and more.
Treatment
First step is to stop the antipsychotic(s). That should be done immediately if the diagnosis of NMS is confirmed or highly likely. In some cases you also have to stop other psychotropic medications like lithium, antidepressants and anticholinergic drugs.
There are some specific treatments available for NMS but these are based on clinical experience and their efficacy is not based upon data from clinical trials and therefore not clear how effective these really are.
-Benzodiazepines are good for agitation and they also have a muscle relaxant effect. I would probably use lorazepam.
-Bromocriptine is a dopamine agonist (works the opposite of antipsychotics that are dopamine antagonists) and might help given that NMS is thought to be caused by too much dopamine blockade in certain brain areas.
-Dantrolene is a muscle relaxant and used to treat malignant hyperthermia. Might be helpful in NMS.
-Electroconvulsive therapy (ECT) is a treatment option for NMS but is not without risk so would not be used as a first-choice treatment.
Many patients need supportive care because complications are common and can be fatal. In some cases patients need to be admitted to the ICU.
Recovery
Most patients recover within 2 weeks but there is a risk of mortality in more severe cases. When a patient has been without symptoms of NMS for a few weeks antipsychotics can be restarted. I would use second generation antipsychotics and lower potency for these patients. It is also important to start with low doses, titrate up slowly and be careful to monitor for a recurrence of NMS symptoms.
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