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

Abstract

BackgroundNeuroleptic 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.ObjectivesThe 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 SourcesCitations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations.Study Eligibility CriteriaEligibility 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 MethodsA standardized method for data extraction and coding was developed for the analysis of eligible case reports.ResultsSix 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.LimitationsCase reports report non-systematic data, therefore analyses may be subject to bias.Conclusions and Implications of Key FindingsClinicians 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-014-0078-0) contains supplementary material, which is available to authorized users.

A successful management with electroconvulsive therapy of neuroleptic malignant syndrome due to amisulpride

“…In the literature, mortality has been also reported in a case with NMS related to amisulpide (15). Consequently, the ECT procedure was applied quickly due to the life-threatening condition (16).…”

A Case Of Neuroleptic Malignant Syndrome Likely Related To Be Clozapine

“…Klozapin ile ilişkili NMS'de klozapinin adrenerjik ve muskarinik blokajına bağlı olarak taşikardi, terleme ve bilinç değişikliği gibi otonomik belirtilerin daha sık görüldü-ğü bildirilmiştir (7) . Olgumuzda da diğer klozapin ile ilişkili NMS'ler gibi terleme ve taşikardi belirgindir.…”

“…Olgumuzda da ateş ilk ortaya çıkan belirtilerden olup, agranülosito-zun tersine lökositoz mevcuttur. Klozapin ile ilişkili NMS'de daha az ekstrapiramidal sistem (EPS) belirtisi gözlendiği ve kreatin kinaz yükselmesinin daha geç olduğu bildirilmiştir (7) . EPS sıklıkla önce tremor şeklinde görülürken, NMS'nin daha geç dönemlerin-de rijidite olarak kendini gösterebilir.…”

Ileus as a Sign of Neuroleptic Malignant Syndrome: A Case Report and Review of the Literature

“…However, several case reports and reviews (4)(5)(6)(7) suggested that NMS may be induced by second-generation antipsychotics, atypically. Preliminary studies indicated that NMS is induced by second-generation antipsychotics with a lower incidence, milder clinical severity and fatal prognosis, and occurs less than NMSs induced by first-generation antipsychotics (8). Results of a systematic review in 2015 found that even antipsychotics most recently marketed are not free of the risk of inducing NMS.…”

“…In addition, clozapine, aripiprazole, and amisulpride can create a more atypical view, e.g. they can show extrapyramidal symptoms with less severity or high fever (8). Notably, several cases of NMS induced by clozapine (CLZ-NMS) presented with different clinical features than first generation antipsychotics (FGZ-NMS) have been reported, in which for example there were no cardinal signs.…”