title: An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method.
abstract: OBJECTIVE
  The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications. The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel.
  
  
  METHODS
  Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure.
  
  
  METHODS
  A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process.
  
  
  METHODS
  After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009.
  
  
  RESULTS
  Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4°F or > 38.0°C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, ≥ 25% above baseline; blood pressure fluctuation, ≥ 20 mm Hg (diastolic) or ≥ 25 mm Hg (systolic) change within 24 hours; tachycardia, ≥ 25% above baseline; and tachypnea, ≥ 50% above baseline.
  
  
  CONCLUSIONS
  These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings.
authors: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA. ronald.gurrera@va.gov
authors: Ronald J
authors: RJ
authors: Gurrera
authors: Stanley N
authors: SN
authors: Caroff
authors: Abigail
authors: A
authors: Cohen
authors: Brendan T
authors: BT
authors: Carroll
authors: Francis
authors: F
authors: DeRoos
authors: Andrew
authors: A
authors: Francis
authors: Steven
authors: S
authors: Frucht
authors: Sanjay
authors: S
authors: Gupta
authors: James L
authors: JL
authors: Levenson
authors: Ahsan
authors: A
authors: Mahmood
authors: Stephan C
authors: SC
authors: Mann
authors: Michael A
authors: MA
authors: Policastro
authors: Patricia I
authors: PI
authors: Rosebush
authors: Henry
authors: H
authors: Rosenberg
authors: Perminder S
authors: PS
authors: Sachdev
authors: Julian N
authors: JN
authors: Trollor
authors: Varadaraj R
authors: VR
authors: Velamoor
authors: Charles B
authors: CB
authors: Watson
authors: Jayne R
authors: JR
authors: Wilkinson
mesh_terms: D032921:Consensus; D003625:Data Collection; D003697:Delphi Technique; D006801:Humans; D058025:Interdisciplinary Studies; D009459:Neuroleptic Malignant Syndrome / Q000175:diagnosis*; D017410:Practice Guidelines as Topic / Q000592:standards*