Chapter 82 Neuroleptic Malignant Syndrome
1 What is neuroleptic malignant syndrome (NMS)?
These features generally appear 24 to 72 hours after the administration of an antipsychotic; however, NMS can also occur with chronic use. Altered mental status is the first presenting symptom in 80% of NMS cases. Mean recovery time after antipsychotic discontinuation is 7 to 10 days but may be prolonged when long-acting depot antipsychotics are implicated. For other common features of NMS, see Box 82-1.
5 What are the diagnostic criteria for NMS?
A. The development of severe muscle rigidity and elevated temperature associated with the use of neuroleptic medication.
B. Two or more of the following: diaphoresis, dysphagia, tremor, incontinence, changes in level of consciousness ranging from confusion to coma, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, and laboratory evidence of muscle injury.
C. The symptoms in criteria A and B are not due to another substance or a neurologic or other general medical condition.
D. The symptoms in criteria A and B are not better accounted for by a mental disorder.
6 What is the differential diagnosis of NMS?
NMS is a clinical diagnosis of exclusion; therefore central, systemic, and toxic causes of hyperthermia, rigidity, rhabdomyolysis, and altered mental status must be excluded. See Box 82-2.
7 Are there specific laboratory findings for NMS?
Elevated serum creatine kinase level of 1000 to 100,000 International Units/L
Leukocytosis (10,000-40,000/mm3)
Elevated lactate dehydrogenase, alkaline phosphatase, and liver transaminase levels
Electrolyte disturbances: hypernatremia, hyponatremia, hyperkalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia
Myoglobinuric acute renal failure: proteinuria, elevated blood urea nitrogen and creatinine levels
9 Which agents have been implicated in the development of NMS?
First- and second-generation antipsychotic medications have been reported to cause NMS:
13 What pharmacologic treatments are useful?
Recent clinical reports suggest that benzodiazepines (oral or parenteral) may ameliorate symptoms of agitation or catatonia and hasten recovery of NMS. A trial of lorazepam 1 to 2 mg parenterally is a reasonable first-line intervention for patients with acute NMS.
Dopamine agonists, such as amantadine and bromocriptine, have been reported to reverse Parkinsonian symptoms, hasten recovery, and decrease mortality rates when used alone or in combination with other pharmacologic agents. Amantadine is generally initiated at 200 to 400 mg/day orally in divided doses. Bromocriptine can be started at 2.5 mg two to three times a day orally with a maximum daily dose of 45 mg. Be advised that bromocriptine can worsen psychosis and hypotension, as well as precipitate vomiting, and must be used with caution. Abrupt discontinuation of bromocriptine can also precipitate rebound symptoms.
Dantrolene may be useful in cases of extreme hyperthermia, rigidity, and hypermetabolism. Typical dosing is 1 to 2.5 mg/kg intravenously initially and may be increased to 1 mg/kg every 6 hours. Side effects include respiratory impairment and hepatic toxicity.
Electroconvulsive therapy (ECT) has been shown to be effective when NMS symptoms are refractory to supportive care and pharmacologic treatment. The typical ECT course was six to 10 bilateral treatments with initial response expected in the first few treatments. During ECT succinylcholine should be avoided in patients with rhabdomyolysis to prevent acute hyperkalemia and cardiovascular complications.
17 Are there alternatives to antipsychotic medications for patients with chronic psychotic illnesses?
Acknowledgments
Key Points Neuroleptic Malignant Syndrome
1. NMS can develop with exposure to any antipsychotic medication—acute or chronic use.
2. When considering the differential diagnosis, the physician should pay particular attention to recent changes in doses and psychotropic polypharmacy.
3. Other agents, such as antiemetic agents, can also cause NMS.
4. Treatment is primarily supportive.
5. In most cases, the most important factors that distinguish NMS from serotonin syndrome are hyperthermia and rigidity.
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