title: Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis.
abstract: BACKGROUND
  Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported.
  
  
  OBJECTIVE
  The aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs.
  
  
  METHODS
  Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations.
  
  
  METHODS
  Eligibility criteria included (a) primary studies reporting data on NMS, with at least 50 % of the sample receiving SGAs; or (b) case reports and case reviews reporting on NMS induced by SGA monotherapy, excluding those due to antipsychotic withdrawal.
  
  
  METHODS
  A standardized method for data extraction and coding was developed for the analysis of eligible case reports.
  
  
  RESULTS
  Six primary studies and 186 individual cases of NMS induced by SGAs were included. Primary studies suggest that SGA-NMS is characterized by lower incidence, lower clinical severity, and less frequent lethal outcome than NMS induced by first-generation antipsychotics. Systematic analysis of case reports suggests that even the most recently marketed antipsychotics are not free from the risk of inducing NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can present with atypical features more frequently than other SGA-NMS, i.e. displaying less intense extrapyramidal symptoms or high fever.
  
  
  CONCLUSIONS
  Case reports report non-systematic data, therefore analyses may be subject to bias.
  
  
  CONCLUSIONS
  Clinicians should be aware that NMS is virtually associated with all antipsychotics, including those most recently marketed. Although apparently less severe than NMS induced by older antipsychotics, SGA-NMS still represent a relevant clinical issue.
authors.affiliation: Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Largo Rosanna Benzi, 10, 16132, Genoa, Italy, martino.belvederi@gmail.com.
authors.forename: Martino
authors.initials: M
authors.lastname: Belvederi Murri
authors.forename: Argentina
authors.initials: A
authors.lastname: Guaglianone
authors.forename: Michele
authors.initials: M
authors.lastname: Bugliani
authors.forename: Pietro
authors.initials: P
authors.lastname: Calcagno
authors.forename: Matteo
authors.initials: M
authors.lastname: Respino
authors.forename: Gianluca
authors.initials: G
authors.lastname: Serafini
authors.forename: Marco
authors.initials: M
authors.lastname: Innamorati
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pompili
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D009459:Neuroleptic Malignant Syndrome / Q000453:epidemiology / Q000209:etiology*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents