drome of 0.01%—0.02% among individuals treated with antipsychotics. The temporal pro- gression of signs and symptoms provides important clues to the diagnosis and prognosis of neuroleptic malignant syndrome. Alteration in mental status and other neurological signs typically precede systemic signs. The onset of symptoms varies from hours to days after drug initiation. Some cases develop within 24 hours after drug initiation, most within the first week, and virtually all cases within 30 days. Once the syndrome is diagnosed and oral antipsychotic drugs are discontinued, neuroleptic malignant syndrome is self—limited in most cases. The mean recovery time after drug discontinuation is 7—10 days, with most individuals recovering within 1 week and nearly all within 30 days. The duration may be prolonged when long-acting antipsychotics are implicated. There have been reports of in- dividuals in whom residual neurological signs persisted for weeks after the acute hyper- metabolic symptoms resolved. Total resolution of symptoms can be obtained in most cases of neuroleptic malignant syndrome; however, fatality rates of 10%—20% have been reported when the disorder is not recognized. Although many individuals do not experi- ence a recurrence of neuroleptic malignant syndrome when rechallenged with antipsy- chotic medication, some do, especially when antipsychotics are reinstituted soon after an episode.
Neuroleptic malignant syndrome is a potential risk in any individual after antipsychotic drug administration. It is not specific to any neuropsychiatric diagnosis and may occur in individuals without a diagnosable mental disorder who receive dopamine antagonists.
Clinical, systemic, and metabolic factors associated with a heightened risk of neuroleptic malignant syndrome include agitation, exhaustion, 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 polymorphisms 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 antipsychotics. Partial or milder forms may be associ- ated with newer antipsychotics, but neuroleptic malignant syndrome varies in severity even with older drugs. Dopamine antagonists used in medical settings (e.g., metoclopra- mide, prochlorperazine) have also been implicated. 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.
or medical conditions, including central nervous system infections, inﬂammatory or au- toimmune conditions, status epilepticus, subcortical structural lesions, and systemic con- ditions (e.g., pheochromocytoma, thyrotoxicosis, tetanus, heat stroke).
resulting from the use of other substances or medications, such as serotonin syndrome; parkinsonian hyperthermia syndrome following abrupt discontinuation of dopamine ag- thesia; hyperthermia associated with abuse of stimulants and hallucinogens; and atropine poisoning from anticholinergics.
In rare instances, individuals with schizophrenia or a mood disorder may present with malignant catatonia, which may be indistinguishable from neuroleptic malignant syn- drome. Some investigators consider neuroleptic malignant syndrome to be a drug- induced form of malignant catatonia.
333.72 (624.02) Medication-Induced Acute Dystonia