Atypical Neuroleptic Malignant Syndrome in Patients Treated with Aripiprazole and Clozapine: A Case-Series Study and Short Review

Abstract

Our cases highlight the atypical features of NMS in patients being treated with combined ari-piprazole and clozapine. Consciousness change, modest elevation of creatine kinase, and leukocytosis were the most consistent findings; hyperthermia accounts for only some of the cases. This is a reminder of the importance of earlier detection of the soft signs and atypical features of NMS under this combined treatment.

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: Nuances and pragmatics of the association

“…Several case reports and case series have accumulated on the occurrence of NMS in patients receiving aripiprazole. 26 , 27 Rigidity and altered mental state seem to be present frequently in such patients, while fever, diaphoresis and tachypnoea are less frequent. NMS has been reported to occur more commonly with fast upward titration of dosages of aripiprazole.…”

“…Aripiprazole has also been implicated in combination antipsychotic regimens, when used alongside other atypical antipsychotics such as clozapine. 27 …”

COVID‐19, neuroleptic malignant syndrome and psychosis

“…Previous cases of NMS occurring in patients on dual aripiprazole and clozapine therapy report consciousness change and only modest elevation of CK, with hyperthermia not typically seen 8 …”

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia

“…The pathophysiological mechanisms of NMS and catatonia remain unclear. However, it is hypothesized that abrupt and extensive D2 dopaminergic blockade of the anterior hypothalamus, corpus stratum, and basal ganglia corresponds to the clinical features of NMS, such as high fever, muscle rigidity, and an altered mental status, respectively ( 10 - 13 ). Additionally, a systematic review of NMS ( 14 ) reported that non-dopaminergic receptors, including serotonergic, adrenergic, and cholinergic receptors, may play an important role in the pathophysiology of NMS in extrapyramidal motor functions ( 15 ), thermoregulation, muscle metabolism ( 16 ), and mental status ( 17 ).…”