Toxicology Case Files from the Utah Poison Control Center
Teaching Points
- Neuroleptic malignant syndrome (NMS) occurs most often with traditional antipsychotics, long-acting injectables, in male patients, in those on lithium therapy, and with concomitant iron deficiency
- Onset is generally over days with a decline in alertness with delirium, slowed movements with increased tone, and eventual rhabdomyolysis, rigidity, and hyperthermia
- Clonus and hyperreflexia should be absent
Case Presentation
A 38-year-old male with history of schizoaffective disorder was brought to the ED with altered mental status. The exact reason for referral was unclear, and it was thought he was near his baseline. Initial workup was unremarkable, and the patient was discharged.
The patient was then found unresponsive on the floor shortly after returning home and was brought back to the ED. CK was elevated to about 5000. He had brisk patellar reflexes, which had been noted during prior examinations before this admission. There was no inducible clonus. Pupils were normal, and nystagmus was absent. Over the next 12 hours, his muscle tone increased until he had moderate rigidity (but not “lead pipe” rigidity).
Extensive workup, including CT, MRI, LP, and EEG, were all unremarkable. Serum carbamazepine and lithium (both home medications) were low.
Further history was obtained that the patient had recently been started on paliperidone 234 mg IM about 1 week prior after recent trials on clozapine (discontinued for possible seizures) and haloperidol.
Given his rhabdomyolysis and hypertonia with a 2-3 day decline shortly after initiating a long-acting injectable antipsychotic together with an otherwise unrevealing workup, a presumptive diagnosis of neuroleptic malignant syndrome was made. The patient received dantrolene 2.5 mg/kg IV with improvement in rigidity.
Over the next few days he had waxing and waning delirium and increased muscle tone treated with benzodiazepines. He developed hyperthermia to 38.0 and received an additional dose of dantrolene 2.5 mg/kg IV. By the 4th day of admission he was somewhat delirious but able to speak in full sentences, and his muscle tone was only slightly increased. His CK peaked at 7000 and trended down. Bromocriptine was given once enteral access was obtained. The patient was eventually discharged to acute rehab as he developed significant weakness and contractures from his prolonged course of NMS.
Neuroleptic Malignant Syndrome
NMS has occurred with every available antipsychotic and is idiosyncratic in nature. Though it may occur at any dose and any time during therapy, it most often occurs with typical high-potency antipsychotics, with long-acting injectables, and within 2 weeks of starting a new agent or increasing a dose.
The classic findings of lead pipe rigidity and hyperthermia do not occur until later in the disease course. Initial symptoms are progressive delirium, decreased mental status, decreased movements with increased muscle tone, and labile heart rate and blood pressure. Notably, clonus and hyperreflexia are absent, and pupils are normal in size. Patients should not be “agitated” in the sense of striking out, getting out of bed, or thrashing as muscle tone is increased and movement becomes progressively more difficult.
The diagnosis may not be readily apparent early on, and other causes of delirium, hyperthermia, and abnormal muscle tone must be ruled out.
Treatment is supportive with IV fluids for dehydration, benzodiazepines to control rigidity, tachycardia, and hypertension, and cooling measures for hyperthermia. Dantrolene is the antidote for malignant hyperthermia and acts by inhibiting calcium release from skeletal muscle sarcoplasmic reticulum. It may be helpful in treating muscle rigidity in NMS but results from case reports are mixed. Hyperthermia is also centrally mediated in NMS, and dantrolene does not treat central hyperthermia, nor do antipyretics.
Dopamine agonists such as bromocriptine, carbidopa/levodopa, and amantadine have been used but are only available in oral formulations and may exacerbate psychosis.