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Drugs R D. 2015 Mar;15(1):45-62. doi: 10.1007/s40268-014-0078-0.

Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis.

Author information

1
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.

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.

PMID:
25578944
PMCID:
PMC4359181
DOI:
10.1007/s40268-014-0078-0
[Indexed for MEDLINE]
Free PMC Article

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