title: Antipsychotic dose escalation as a trigger for neuroleptic malignant syndrome (NMS): literature review and case series report.
abstract: BACKGROUND
  "Neuroleptic malignant syndrome" (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined.
  
  
  METHODS
  We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of "rapid dose escalation" was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and "rapid escalators" and "non rapid escalators" were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1-15 to 346.9 mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators.
  
  
  CONCLUSIONS
  Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose - alongside other known risk factors - may also be important in the development of NMS.
authors.affiliation: Institute of Health an Wellbeing, Mental Health and Wellbeing, Gartnavel Royal Hospital, University of Glasgow, 1055 Great Western Road, Glasgow G12 0XH, Scotland, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Langan
authors.forename: Daniel
authors.initials: D
authors.lastname: Martin
authors.forename: Polash
authors.initials: P
authors.lastname: Shajahan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D009459:Neuroleptic Malignant Syndrome / Q000175:diagnosis / Q000209:etiology*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents