Article

Neuroleptic malignant syndrome under treatment with antidepressants? A critical review.

University of Bonn, Bonn, North Rhine-Westphalia, Germany
European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.36). 02/1998; 248(5):231-9. DOI: 10.1007/s004060050043
Source: PubMed

ABSTRACT Neuroleptic malignant syndrome (NMS) is a rare complication of treatment with neuroleptics. The pathophysiology is not fully known. A dopaminergic transmission block in the basal ganglia and hypothalamus is thought to be the pathophysiological mechanism of NMS. Several cases of NMS have been reported, precipitated by medication without a direct effect on the dopaminergic system. This Medline analysis concerns 23 cases of antidepressant-induced NMS reported in the literature with the differing pathophysiological hypotheses on the precipitation of NMS. The results indicate no hard evidence of an antidepressant-evoked NMS. However, various hypotheses assuming an disturbed balance of the dopaminergic and non-dopaminergic system may be relevant in animal studies, but are without clinically relevant proof presently. An antidepressant-induced NMS is a very rare complication on the basis of pretreatment with neuroleptics causing chronic dopamine blockade and elevated plasma level of neuroleptics due to comedicated antidepressants.

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    ABSTRACT: 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. 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. Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations. 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. A standardized method for data extraction and coding was developed for the analysis of eligible case reports. 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. Case reports report non-systematic data, therefore analyses may be subject to bias. 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.
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