Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis.
Drugs R D. 2015 Mar ;15(1):45-62. PMID: 25578944
Martino Belvederi Murri
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.