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

Department of Psychiatry, University of Bochum, 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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    ABSTRACT: Neuroleptic malignant syndrome (NMS) is associated with the administration of antipsychotic agents and other drugs such as l-dopa, antidepressants, and antihistaminic agents. Unexpected changes in mental status, new-onset catatonia, episodic tachycardia, tachypnea, hypertension, dysarthria, dysphagia, diaphoresis, sialorrhea, incontinence, low-grade temperature elevations, and rigidity should arouse suspicion. Several lines of evidence provide support for the involvement of dopamine. Most of the drugs implicated in NMS are D2 dopamine receptor antagonists. Central noradrenergic activity is also possibly related to the disorder, as sympathetic hyperactivity is associated with the active phase of NMS. Currently, the definitive role of GABA deficiency in NMS is yet to be established. Differential diagnosis should include malignant hyperthermia, lethal catatonia, lithium toxicity, serotonin syndrome, and heat stroke. A high degree of suspicion and the discontinuation of antipsychotic agents even if the diagnosis is not established are essential for the safety of the patient. Treatment of NMS should be individualized and be based empirically on the character, duration, and severity of the clinical signs and symptoms noted. The initial step in the treatment of NMS is the removal of the offending agent. Full-blown NMS is a serious condition and requires immediate supportive, nutritive, and electrolyte therapies. The administration of drugs that can improve NMS, such as IV dantrolene and/or oral bromocriptine, may also be taken into consideration, based on the severity and nature of the NMS.
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