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Drugs in R&D
Published in: Drugs in R&D 1/2015

Open Access 01-03-2015 | Systematic Review

Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

Authors: Martino Belvederi Murri, Argentina Guaglianone, Michele Bugliani, Pietro Calcagno, Matteo Respino, Gianluca Serafini, Marco Innamorati, Maurizio Pompili, Mario Amore

Published in: Drugs in R&D | Issue 1/2015

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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.

Objectives

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.

Data Sources

Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations.

Study Eligibility Criteria

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.

Study Appraisal and Synthesis 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.

Limitations

Case reports report non-systematic data, therefore analyses may be subject to bias.

Conclusions and Implications of Key Findings

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.
Appendix
Available only for authorised users
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Metadata
Title
Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis
Authors
Martino Belvederi Murri
Argentina Guaglianone
Michele Bugliani
Pietro Calcagno
Matteo Respino
Gianluca Serafini
Marco Innamorati
Maurizio Pompili
Mario Amore
Publication date
01-03-2015
Publisher
Springer International Publishing
Published in
Drugs in R&D / Issue 1/2015
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI
https://doi.org/10.1007/s40268-014-0078-0

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