Medline ® Abstracts for References 2,4-6

Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic medication. The author describes three new cases and reviews 50 others published in the past 5 years. Demographic and clinical features, diagnosis, treatment, outcome, and pathophysiology are critically reviewed, and a new set of diagnostic criteria, incorporating physical signs and routine laboratory tests, is proposed.

Neuroleptic malignant syndrome is a rare but potentially fatal reaction associated with neuroleptic drugs. It occurs in about 0.2% of patients treated with neuroleptics. Risk factors include previous episodes, dehydration, agitation, and the rate and route of neuroleptic administration. Although NMS has been reported in patients with diverse psychiatric diagnoses, as well as in normal subjects, patients with organic brain disorders or mood disorders, particularly when receiving lithium, may be at increased risk. Standardized criteria for the diagnosis of NMS have been developed and emphasize the classic findings of hyperthermia, muscle rigidity, mental status changes, and autonomic dysfunction. The syndrome lasts 7 to 10 days in uncomplicated cases receiving oral neuroleptics. Treatment consists primarily of early recognition, discontinuation of triggering drugs, management of fluid balance, temperature reduction, and monitoring for complications. Use of dopamine agonists or dantrolene or both should be considered and may be indicated in more severe, prolonged, or refractory cases. Electroconvulsive therapy has been used successfully in some cases and is particularly useful in the post-NMS patient. As a result of these measures, mortality from NMS has declined in recent years although fatalities still occur. Neuroleptics may be safely reintroduced in the management of the majority of patients recovered from an NMS episode, although a significant risk of recurrence does exist, dependent in part on time elapsed sincerecovery and dose or potency of neuroleptics used. Data drawn from clinical observations and basic studies support the primary role of an acute reduction in brain dopamine activity in the development of NMS. Additional studies of facilitating cofactors may lead to innovative risk-reduction strategies and the development of safer neuroleptic drugs.

OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a serious iatrogenic condition. This report reviews the world literature to characterize the syndrome and evaluate factors that promote early detection and effective intervention.

METHOD: The review identified 77 NMS cases (49 males, 27 females, 1 gender unknown); ages ranged from 0.9 to 18 years (mean 14.8 +/- 3.96). Univariate and multiple regression analyses were applied to 38 variables to identify early signs of the disorder, to identify correlates of outcome, and to evaluate treatments.

RESULTS: The duration of NMS spanned from 1 to 119 days. Nine percent of patients died and 20% resolved with serious sequelae. Patients receiving low-potency neuroleptics had a poorer outcome (p = .01). Fever was related to longer duration of illness (p = .03). Anticholinergics and bromocriptine were effective and without fatalities, but dantrolene was not useful in this sample of children and adolescents.

CONCLUSIONS: Early detection and appropriate interventions appear important in moderating the course and outcome of NMS.

PURPOSE: Neuroleptic malignant syndrome (NMS) is a rare and life threatening condition usually defined as a complication of treatment with antipsychotics characterized by severe rigidity, tremor, fever, altered mental status, autonomic dysfunction, and elevated serum creatine phosphokinase and white blood cell count. The literature on this topic is rather extensive, but many aspects related to the syndrome are thought to be controversial. The aim of this paper, written with the clinician in mind, is to summarize some of the most prominent controversies that may have importance in usual clinical practice.

METHODS: The literature was searched for reviews, reports on the series of cases, individual case reports of NMS, and other clinically and theoretically important information.

RESULTS: There are controversies associated with virtually all important aspects of NMS. At the moment, it is not clear if this drug reaction is idiosyncratic or not, what diagnostic criteria are the most appropriate for usual clinical practice, and it seems that the estimated incidence is not in accordance with the number of treated patients. There are rather different approaches to the pathophysiological mechanisms, differential diagnosis, and treatment.

CONCLUSIONS: Some of the controversies related to NMS have an influence on our understanding of the condition and may have importance in clinical practice. There is a need for further research that should elucidate these controversies.