Atypical Neuroleptic Malignant Syndrome Precipitated by Clozapine and Quetiapine Overdose: A Diagnostic Challenge

Abstract

Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, but life-threatening adverse reaction associated with the use of antipsychotic drugs. It is characterized by a tetrad of fever, rigidity, autonomic instability, and altered mental status. Failure to diagnose NMS early and institute appropriate treatment can result in serious medical complications and death. While diagnostic criteria for NMS exist, atypical presentations that lack one or more characteristic features pose a diagnostic dilemma to clinicians. The concept of atypical NMS has been proposed for such cases but remains controversial. We report a case of atypical NMS associated with overdose on clozapine and quetiapine and discuss the diagnostic challenges of an atypical presentation. In this case, the diagnosis was delayed due to the absence of rigidity, but later made after serum creatine kinase was found to be markedly elevated. Clinicians should have a high index of suspicion for NMS. Routine checking and trending of serum CK in patients on antipsychotic drugs who present with features of NMS is recommended to facilitate diagnosis. Future research is needed to define and validate threshold scores for existing diagnostic criteria for NMS.

Keywords: Neuroleptic malignant syndrome; antipsychotics; clozapine; creatine kinase; diagnosis; drug overdose; quetiapine.