Snapshot A 32-year-old woman is brought to the psychiatric emergency department by emergency medical service for a suicidal attempt. The patient expressed to the hospital staff that she wishes to end her life due to concerns someone is attempting to kidnap her. She has a medical history of schizophrenia and has not been adherent to her aripiprazole. The patient attempted to attack 1 of the security guards due to the belief that he is involved in her kidnapping. She was given multiple doses of intramuscular haloperidol. Approximately 2 days later, the patient's temperature is 102°F (38.9°C), blood pressure is 163/95 mmHg, pulse is 115/min, and respirations are 26/min. On physical examination, the patient is diffusely rigid and is profusely diaphoretic. Introduction Overview life-threatening neurologic and psychiatric emergency associated with neuroleptic (antipsychotic) medication use classic clinical syndrome tetrad altered mental status fever rigidity autonomic instability Epidemiology Demographics typically seen in young adults can occur at any age Risk factors antipsychotic use first- and second-generation antiemetic use e.g., metoclopramide and prochlorperazine antiparkinson medication withdrawal also called neuroleptic malignant-like syndrome or parkinsonism hyperpyrexia syndrome ETIOLOGY Pathophysiology unknown but dopamine receptor blockade in the central nervous system is believed to be involved Associated conditions psychiatric disorders that require high or frequent doses of antipsychotic medications Presentation History tetrad usually occurs over the course of 1-3 days after neuroleptic use Physical exam altered mental status agitated delirium confusion catatonia mutism fever ≥ 38°C rigidity typically diffuse can be described as a "lead-pipe rigidity" patients may also have a tremor (45-92% of cases) autonomic instability tachycardia patients may develop dysrhythmias hypertension or labile blood pressure tachypnea diaphoresis hyporeflexia Studies Labs ↑ creatine kinase usually > 1000 U/L basic metabolic panel hypo- or hypernatremia hyperkalemia hypomagnesemia hypocalcemia metabolic acidosis acute renal failure may occure if myoglobinuria ↓ iron concentration sensitive but not specific Differential Serotonin syndrome key distinguishing factors acute onset myoclonus hyperreflexia mydriasis (large pupils) Malignant hyperthermia key distinguishing factorss offending agents are halogenated inhalational anesthetics succinylcholine Treatment Prevention Conservative use of antipsychotics Gradual titration of antopsychotics Lifestyle supportive care indication first-line in preventing further complications intravenous fluids to prevent dehydration and acute kidney injury from myglobinuria electrolyte repletion to prevent cardiac arrythmias and seizures Pharmacologic discontinue the offending agent indication first-line to prevent further progression of neuroleptic malignant syndrome benzodiazepines indication usually initially used along with dantrolene in moderate or severe cases medication lorazepam diazepam dantrolene indication usually given with benzodiazepines in moderate or severe cases effective in relaxing skeletal muscles bromocriptine indication administered after benzodiazepines and dantrolene is administered in order to restore dopaminergic tone alternative agent amantadine Complications Seizure Cardiac dysrhythmia Myocardial infarction Respiratory failure Hepatic failure Acute renal failure Deep venous thrombosis Disseminated intravascular coagulation Prognosis Natural history of disease most cases resolve within 2 weeks Survival with treatment improved