Neuroleptic Malignant Syndrome (NMS) on Clozapine with aPotential Atypical Interaction with Paliperidone

Neuroleptic Malignant Syndrome (NMS) associated with the use offirst-generation antipsychotics is a widely known phenomenon.This idiosyncratic reaction is less significant with the use of second-generation antipsychotics, and only a few cases in the literatureexist, describing this reaction with clozapine use. While being titrated on clozapine, the patient developed major and minor criteriafeatures of NMS as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-5) criteria except for fever, acore symptom which created diagnostic uncertainty. Initially, clozapine was temporarily discontinued due to his deterioratingmental and physical state. A rechallenge was considered at a much lower dose, but due to a rapid increase in his creatininekinase (CK) levels within a 12-hour timeframe, clozapine was permanently stopped. The evidence further suggests that thepresentation of NMS for patients on this medication may be different to the classical presentation, and other criteria fordiagnosis are suggested, which may lower the threshold for investigating NMS for patients on clozapine.