Malignant neuroleptic syndrome

This devastating disorder was seemingly so bizarre, unexpected, and inexplicable that physicians for years literally refused to believe their eyes. Seven years after the introduction of the drugs into North America, Leo Hollister (1961) reviewed their side effects in the New England Journal of Medicine. In two separate places, he referred to syndromes that probably were NMS. He described a bizarre dystonic syndrome that can be confused with hysteria, tetanus, encephalitis or other acute nervous-system disorders a rare fatality may occur. Later, he mentioned, Other clinical syndromes attributed to central nervous-system effects of these drugs have resembled acute encephalitis, myasthenia gravis, bulbar palsy or pseudotabes.  

Delay and Deniker (1968) were already able to identify many of the components of NMS, including pallor, hyperthermia, a severe psychomotor syndrome with akinesia and stupor, or hypertonicity with varying dyskinesias. They warn that at the first suspicion, one must stop medication immediately and completely. They were already aware of fatalities. That the syndrome was named and definitively identified in English in 1968 is most remarkable in light of the failure of drug companies to give it formal recognition until compelled to do so by the FDA almost 20 years later (see chapter 13 for further discussion). 

NMS is characterized by such symptoms as severe dyskinesia or akinesia, temperature elevation, tachycardia, blood pressure fluctuations, diaphoresis, dyspnea, dysphagia, and urinary incontinence (Coons et al., 1982). The DSM-IV-TR establishes criteria of severe muscle rigidity and elevated temperature plus 2 more of 10 associated features, including sweating, swallowing problems, tremor, incontinence, changes in level of consciousness from confusion to coma, mutism, elevated heart rate, unstable blood pressure, elevated white count, or laboratory evidence of 

Almost all patients were agitated shortly before developing NMS, suggesting to Rosebush and Stewart (1989) that they were undergoing akathisia. White blood cell counts were elevated in all cases, dehydration was common, and lab tests showed a broad spectrum of enzymatic abnormalities, including indications of muscle breakdown such as an elevated CPK. 

If unrecognized, as too often happens, NMS can be fatal in more than 20% of cases. The syndrome frequendy leaves the surviving patient with permanent dyskinesias and dementia (see chapter 5). 

---

Kosten TR, Kleber HD Rapid death during cocaine abuse a variant of the neuroleptic malignant syndrome Am J Drug Alcohol Abuse 14 335-346, 1988 Kosten TR, Kleber HD, Morgan C Treatment of cocaine abuse with buprenorphine. Biol Psychiatry 26 637—639, 1989... 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

The patient may be alert and oriented, withdrawn or lethargic, or have an acute brain syndrome. There is a high incidence of rhabdomyolysis and hyperthermia in PCP-induced catatonic syndrome. Some patients have the neuroleptic malignant syndrome or develop it after administration of haloperidol. 

The neuroleptic malignant syndrome is characterized by hyperthermia (temperature over 103 °F without evidence of infection), altered sensorium, muscle rigidity, and autonomic disturbances, usually profuse diaphoresis, hypersali vat ion, bronchorrhea, and urinary retention. 

Once neuroleptic malignant syndrome (NMS) develops, signs and symptoms may escalate over 24—72 h and may have a prolonged clinical course... 

Rare Neuroleptic malignant syndrome, hematologic abnormalities... 

Kosten, T. and Kleber, H.D. Sudden death in cocaine abusers relation to neuroleptic malignant syndrome. Lancet. 1 1198, 1987. 

Kosten, T.R. and Kleber, H.D. Rapid death during cocaine abuse a variant of neuroleptic malignant syndrome. Am J. Drug Alcohol Abuse. 14 335, 1988. 

SECTION 13 Psychiatric Disorders Neuroleptic Malignant Syndrome... 

Neuroleptic malignant syndrome is an acute iatrogenic condition caused by neuroleptics, characterized by tremor, catatonia, fluctuating consciousness, hyperthermia, and cardiovascular instability. It is relatively uncommon, occuring in 1-1.5% of patients but is fatal in 11-38%, most often due to cardiovascular collapse (Jahan et al. 1992). The pathogenesis of neuroleptic malignant syndrome is poorly understood, but it is believed to result from altered dopamine and serotonin transmission in the hypothalamus, spinal cord, and striatum. Treatment includes discontinuation of neuroleptics and administration of drugs that increase dopamine transmission bromocriptine or L-dopa (Jahan etal. 1992 Baldessarini 1996). 

Jahan MS, Farooque AI, Wahid Z. (1992). Neuroleptic malignant syndrome. J Natl Med Assoc. 

Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with promethazine alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (eg, irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias). 

Neuroleptic malignant syndrome (NMS) NMS is a potentially fatal condition reported in association with antipsychotic drugs and with amoxapine. 

---