Medication-Induced Movement Disorders 711
Risk and Prognostic Factors
Neuroleptic malignant sy ndrome is a potential risk in an y individual after antipsychotic
drug administration. It is not specific to an y neuropsychiatric diagnosis and may occur in
individuals without a diagnosable mental disorder who receive dopamine antagonists.
Clinical, systemic, and metabolic factors associ ated with a heightened risk of neuroleptic
malignant syndrome include agitation, exhaus tion, dehydration, and iron deficiency. A
prior episode associated with antipsychotics has been described in 15%–20% of index
cases, suggesting underlying vulnerability in  some patients; however, genetic findings
based on neurotransmitter receptor polymorphi sms have not been replicated consistently.
Nearly all dopamine antagonists have been associated with neuroleptic malignant
syndrome, although high-potency antipsychotics  pose a greater risk compared with low-
potency agents and newer atypical antipsychoti cs. Partial or milder forms may be associ-
ated with newer antipsychotics, but neurolep tic malignant syndrome  varies in severity
even with older drugs. Dopami ne antagonists used in medical settings (e.g., metoclopra-
mide, prochlorperazine) have also been impl icated. Parenteral administration routes,
rapid titration rates, and higher total drug dosages have been associated with increased
risk; however, neuroleptic malignant syndrome  usually occurs within the therapeutic dos-
age range of antipsychotics.
Differential Diagnosis
Neuroleptic malignant syndrome must be di stinguished from other serious neurological
or medical conditions, including central nerv ous system infections, inflammatory or au-
toimmune conditions, status ep ilepticus, subcortical structur al lesions, and systemic con-