A 25-year-old man is brought to the emergency department due to severe agitation and aggressive behavior. He speaks loudly and rapidly, stating that he has "superpowers" of mind control and that violence is the only way to defend against "the conspiracy." The patient has a history of bipolar disorder and is prescribed olanzapine, lithium, and fluoxetine, although it is unclear if he has been compliant. The patient requires several doses of medication in the emergency department to calm down and is subsequently admitted to the hospital for further psychiatric evaluation. The following night he is found lying very still on his bed and does not respond to questions. Temperature is 40.6 C (105.1 F), blood pressure is 157/90 mm Hg, pulse is 102/min, and respirations are 20/min. Examination is significant for diaphoresis and diffuse rigidity in upper and lower extremities. Which of the following is the most likely explanation for this patient's current symptoms?
Neuroleptic malignant syndrome | Serotonin syndrome | |
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This patient is experiencing a manic episode with psychotic features and most likely received multiple doses of antipsychotic medication to control his agitation in the emergency department. His hyperthermia, sympathetic hyperactivity (eg, diaphoresis, tachycardia), severe muscle rigidity (frequently described as "lead-pipe rigidity"), and altered mental status are characteristic of neuroleptic malignant syndrome (NMS).
NMS is a potentially life-threatening adverse reaction to antipsychotics (ie, neuroleptics) that typically presents 1-3 days after initiation or dose escalation. It is thought to be caused by antagonism of central dopaminergic systems involved in thermoregulation and regulation of muscle tone and movement. Treatment involves cessation of the causative agent; benzodiazepines and dantrolene (a postsynaptic muscle relaxant) are used for treating severe cases.
(Choices A, B, and C) Antipsychotic D2 dopamine receptor antagonism in the nigrostriatal pathway can cause a variety of reactions (known as extrapyramidal symptoms) that can be confused with NMS. Acute dystonic reactions involve distressing contractions of the neck, mouth, and tongue. Akathisia is a subjective feeling of intense restlessness and an inability to sit still. Drug-induced parkinsonism manifests as rigidity, bradykinesia, and tremor. None of these conditions involves altered mental status, hyperthermia, or sympathetic hyperactivity.
(Choice D) Lithium is a mood stabilizer used in bipolar disorder but is not used to control acute agitation and psychosis. Acute lithium toxicity typically begins with nausea, vomiting, and diarrhea, with neuromuscular signs developing later.
(Choice F) Although serotonin syndrome (due to overdose or combinations of serotonergic drugs) can also present with mental status changes, hyperthermia, and sympathetic hyperactivity, it typically presents with neuromuscular hyperactivity (eg, clonus, hyperreflexia) as opposed to the diffuse rigidity seen in NMS and in this patient.
Educational objective:
Neuroleptic malignant syndrome (NMS) is an adverse reaction to antipsychotic medication characterized by severe "lead-pipe" rigidity, hyperthermia, sympathetic hyperactivity, and mental status changes. NMS is characterized by severe rigidity rather than the neuromuscular irritability (eg, hyperreflexia, myoclonus) seen in serotonin syndrome.