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.

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.

• Authors: Martino Belvederi Murri, Argentina Guaglianone, Michele Bugliani, Pietro Calcagno, Matteo Respino, Gianluca Serafini, Marco Innamorati, Maurizio Pompili, Mario Amore
• Journal: Drugs in R&D (Drugs R D) Vol. 15 Issue 1 Pg. 45-62 (Mar 2015) ISSN: 1179-6901 [Electronic] New Zealand
• PMID: 25578944 (Publication Type: Journal Article, Review, Systematic Review)

Chemical References

• Antipsychotic Agents

Topics

• Antipsychotic Agents (adverse effects)
• Humans
• Incidence
• Neuroleptic Malignant Syndrome (epidemiology, etiology)
• Severity of Illness Index