Neuroleptic Malignant Syndrome in Emergency Medicine Medication

Pharmacotherapy recommendations are from noncontrolled prospective and retrospective studies and case reports; no controlled studies exist. The mortality rate has declined from approximately 20% to less than 10%. The decrease may be due to improved supportive care modalities. Whether the addition of dantrolene to dopamine agonists will improve the prognosis is unclear. A recent review of case reports indicates that combining dantrolene with other pharmacotherapy prolongs the recovery period. Using dantrolene as monotherapy seemed to be associated with increased mortality. Dopaminergic medications can be especially useful if the NMS was caused by withdrawal of anti-Parkinson medication.^{[7, 8, 9]}

Class Summary

Dopamine agonists reverse the dopamine D2-receptor blockade produced by neuroleptics. In retrospective studies, agonists appear to decrease mortality and shorten the course of NMS.

Bromocriptine (Parlodel)

Semisynthetic, ergot alkaloid derivative. Strong, dopamine D2-receptor agonist. Partial dopamine, D1-receptor agonist.

May relieve akinesia, rigidity, and tremor associated with Parkinson disease. Stimulates dopamine receptors in the corpus striatum.

Approximately 28% is absorbed from the GI tract and metabolized in the liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine.

Initiate at low dosage. Slowly increase dosage to individualize therapy. Assess dosage titration q2wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.

Amantadine (Symmetrel)

May act to release dopamine from dopaminergic terminals and other central sites.

Levodopa and carbidopa (Sinemet)

Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system. Absorption is decreased by meals, which include other large neutral amino acids. Only patients with meaningful motor fluctuations need consider a low protein or protein redistributed diet. Greater consistency of absorption achieved when levodopa taken >1 h after meals. Nausea often is reduced if levodopa is taken immediately following meals. Some patients with nausea benefit from additional carbidopa in doses up to 200 mg/d. Half-life of levodopa/carbidopa is approximately 2 h.

Provide at least 70-100 mg/d carbidopa. When more carbidopa required, substitute 25/100 tab for each 10/100 tab. When more levodopa required, substitute 25/250 tab for the 25/100 or 10/100 tab.

Sustained-release formulation of levodopa/carbidopa is more slowly absorbed and provides more sustained levodopa levels than the immediate-release dosage form. Effective as immediate-release formulation when levodopa is required initially and may be more convenient when fewer intakes are desired.

Most patients have been adequately treated with 2-8 tab/d (divided doses) at intervals of 4-8 h while awake. Higher doses (>12 tab/d) and intervals < 4 h have been used but are not usually recommended. If < 4 h interval used or if divided doses are not equal, give smaller doses at end of day. Allow at least a 3-d interval between dosage adjustments. May administer as whole or half tab, which should not be crushed or chewed.

Class Summary

These agents stimulate muscle relaxation by modulating skeletal muscle contractions at site beyond myoneural junction and acting directly on muscle itself.

Dantrolene (Dantrium)

Inhibits ionized calcium release from sarcoplasmic reticulum and results in direct muscle relaxation. Used to treat NMS-associated muscular rigidity and hyperthermia.

Based on retrospective studies, the addition of dantrolene to bromocriptine does not appear to offer additional advantage. Dantrolene therapy alone appears to shorten the duration of illness, but use is controversial. Reduction of fever and rigidity is not immediate but occurs over a mean of 1.7 d. When rapid rigidity reduction is necessary, alternative means (eg, neuromuscular paralysis) may be preferable. A recent review of case reports indicates that adding dantrolene to other medication prolongs the course of NMS. Therapy with dantrolene alone had increased mortality. The only benefit to dantrolene was in patients who prior to NMS had been on a neuroleptic monotherapy.

Most patients respond to 400 mg/d or less.