A 22-year-old man Is brought in by ambulance to the emergency department with profound rigidity and extreme agitation for the past 1 hour. His mother relays that the patient was previously well but woke up this morning feeling very hot with no symptomatic relief with acetaminophen. She recalls the patient visiting a psychiatrist 7 days ago following concerns that he could hear voices telling him to kill himself that no one else around him was able to hear. She is unsure of the outcome of this appointment. Vital signs are temperature 39.5° C (103.1° F), pulse 115 beats/min, and respirations 22/min. Systolic blood pressure is noted to fluctuate between 133mmHg and 160mmHg. On physical examination, the patient appears diaphoretic and displays mutism. Neurological examination reveals generalized muscle rigidity and bradyreflexia.
Pertinent laboratory studies include the following:
- Leukocyte count - 21,000/mm3
- Creatine kinase - 2,000 U/L
Intravenous access is obtained, and the patient is transferred to intensive care unit (ICU).
Which of the following medications would not be useful in managing this patient?
- A) Amantadine
- B) Bromocriptine
- C) Cyproheptadine
- D) Dantrolene
- E) Diazepam
This is a case of neuroleptic malignant syndrome (NMS). NMS is a rare but life-threatening reaction to initiation or rapid up-titration of antipsychotic agents (especially first-generation antipsychotics) and certain anti-emetics (e.g., metoclopramide, promethazine). It has also been associated with withdrawal of dopaminergic Parkinson disease medications. Though the pathogenesis of NMS is unknown, dopamine receptor blockade remains the most common theory. NMS has an onset within days to weeks and typically presents with a tetrad of clinical features: fever, rigidity, altered mental status, and autonomic instability. The mainstay treatment for NMS involves cessation of causative agents and supportive care. Medical therapy is required in patients with moderate or severe NMS.
Cyproheptadine is an antihistamine with anti-serotonergic properties, implicated in the management of serotonin syndrome (SS) but not NMS. SS is caused by the use of selective serotonin reuptake inhibitors (SSRIs) and can present similarly to NMS, making it difficult to distinguish. SS tends to present more quickly than NMS (within 24 hours) and is characterized by signs of hyperreactivity (hyperreflexia, clonus, tremor).
Amantadine is used as an alternative to bromocriptine in the management of NMS.
Bromocriptine is a dopamine agonist used to reverse the antidopaminergic effect of antipsychotic drugs in NMS.
Dantrolene is a direct-acting skeletal muscle relaxant used in NMS for reducing muscle rigidity and heat production.
Diazepam is a benzodiazepine that can be used to manage agitation in patients with NMS.
Key Learning Point
Neuroleptic malignant syndrome is a rare but life-threatening emergency that requires prompt diagnosis and management. Medications used to treat NMS include amantadine, bromocriptine, dantrolene, and diazepam. Serotonin syndrome is an important differential diagnosis to consider in patients presenting with altered mental status, neuromuscular excitation, and autonomic dysfunction.