History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors include exposure to antipsychotic medications, abrupt withdrawal of dopaminergic drugs/dopamine agonists, previous NMS, and structural brain abnormality.
Take a careful drug history to ascertain whether the patient has been treated with a dopamine antagonist (or stopped or rapidly reduced a dopamine agonist) within the last 72 hours.[35][36]
NMS can be caused by any antipsychotic medication but is often associated with the use of first-generation antipsychotics such as haloperidol.[35] NMS can also occur with second-generation antipsychotics such as clozapine, olanzapine, quetiapine, and risperidone.[35][36]
NMS is most likely to develop following initiation of an antipsychotic (most commonly within 3 to 9 days of starting treatment but can occur after the patient has been taking the drug for a longer period of time) or an increase in the dose.[14][24][26][35][44][48][49][50][51]
Some association has been reported with exposure to dopamine antagonists/modulators other than antipsychotics, including metoclopramide, lithium, tolcapone, amantadine, and certain (particularly tricyclic) antidepressants.[1][2][3][29]
This list of causative drugs is not exhaustive, and you should consult your drug formulary for a complete list of drugs where NMS or NMS-like symptoms have been reported.
Almost all patients develop symptoms within 30 days, with 16% developing symptoms within 24 hours of drug initiation and 66% within 1 week.[24][38]
hyperthermia
Temperature >38℃ (>100.4°F) on at least two occasions, measured orally.[36][38] The patient’s temperature can rise quickly; aggressive external cooling interventions may be required.
May occur simultaneously with excessive sweating or flushing, indicating a disruption of normal thermoregulation, though may be delayed by up to 24 hours after onset of these symptoms.
muscle rigidity
Patients can develop new muscle rigidity, or have worsening of pre-existing muscle rigidity. Generalised rigidity, described as 'lead pipe' in its most severe form and usually unresponsive to antiparkinsonian agents, is a cardinal feature and may be associated with other neurological symptoms (e.g., tremor, sialorrhoea, akinesia, dystonia, trismus, myoclonus, dysarthria, dysphagia, rhabdomyolysis).[38]
altered mental status
Confusion, delirium, or stupor.
sympathetic nervous system lability
Blood pressure elevation or fluctuation, sweating, urinary incontinence, or pallor.
Practical tip
Sweating associated with NMS is often described by the patient as being greasy in nature.
hypermetabolism
25% increase of heart rate and 50% increase in respiratory rate above baseline.
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