Epidemiology
The true incidence of NMS is not known because the available evidence is inconclusive.[8] Estimates range from 0.02% to 3%.[9] An important limitation when considering published estimates is that they are almost exclusively incidence proportions (number of new cases over a period of time divided by number of persons at risk at the beginning of the time period) rather than true incidence rates (number of new cases over a period of time divided by the person-time at risk).[8] Reported incidence has declined over the last 20 years, which may reflect greater awareness with heightened vigilance and more prompt clinical intervention. Systematic reporting bias may play a part.[8] Other contributing factors may include an evolving practice trend toward the use of second-generation antipsychotic medications, and caution in using high initial doses of antipsychotics.
NMS has been reported to be more common in male than in female patients, but larger studies have not consistently found this.[10] A systematic review and meta-analysis that specifically examined sex and age distribution in NMS found a male to female ratio of 1.5.[11]
Pre-existing structural brain abnormality, catatonia, and older age are associated with an increased risk.[12][13] Mortality associated with NMS appears to vary.[8][12][14][15][16][17][18] Two large studies reported a rate between 8% and 9%.[10][19] One systematic review found that respiratory difficulties, hyperthermia severity, and older age were associated with increased mortality in those with NMS.[20]
Risk factors
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]
Studies have found that rigidity is more frequent and mortality is higher with first-generation antipsychotics.[19][37]
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]
Administration of high doses of antipsychotics at onset of treatment and intramuscular administration may increase the risk.
Patients with agitation require intramuscular antipsychotics.[27] Whether the clinical setting (physical agitation and emotional turmoil) predisposes to the development of NMS is not currently known.
Motor restlessness is considered a risk factor for developing NMS.[27]
A systematic review and meta-analysis that specifically examined sex and age distribution in NMS found that men are approximately 50% more likely to be diagnosed with NMS at any age compared with women (male to female ratio of 1.5).[11]
It has been suggested that low serum iron may contribute to acute hypodopaminergia.[32][33]
Although acute hypoferraemia has been observed in a significant proportion of NMS cases, iron does not readily cross the blood-brain barrier, so it is unlikely that acute changes in serum iron play a causative role in NMS. However, chronically low iron levels could affect brain dopamine function over time.
This may be an independent risk factor, secondary to prolonged agitation and/or diaphoresis with poor oral intake, or may be linked by association to sepsis.[27]
Use of this content is subject to our disclaimer