title: Atypical neuroleptic malignant syndrome in patients treated with aripiprazole and clozapine: a case-series study and short review.
abstract: OBJECTIVE
  Neuroleptic malignant syndrome (NMS) requires emergency treatment and can be fatal. Combined aripiprazole and clozapine therapy is rarely used in clinical settings, and NMS related this combination still lacks evaluation. Herein, we present two cases of atypical NMS treated with aripiprazole and clozapine.
  
  
  METHODS
  Case 1 was a schizophrenic male with a history of NMS under treatment with aripiprazole 20 mg. He was hospitalized and maintained with aripiprazole 5 mg and clozapine 225 mg. On the 25th day, atypical NMS occurred with rigidity, elevated creatine kinase, and stupor, which subsided with supportive therapy. He was discharged under treatment with aripiprazole 15 mg and fluoxetine 60 mg. Case 2 was a female with schizoaffective disorder without a history of NMS. She was hospitalized and maintained with clozapine 50 mg and aripirazole 30 mg. On the 11th day, atypical NMS occurred with mild fever, delirium, and rigidity, which subsided under supportive therapy.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Ping-Tao
authors.initials: PT
authors.lastname: Tseng
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Chih-Hua
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Yu-Shian
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan.
authors.forename: Ching-Kuan
authors.initials: CK
authors.lastname: Wu
authors.affiliation: EDa hospital, Kaohsiung, Taiwan.
authors.forename: Yen-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Tsyr-Huey Mental Hospital, Kaohsiung Jen-Ai's Home, Taiwan johnwayroom@gmail.com.
authors.forename: Weilun
authors.initials: W
authors.lastname: Chung
mesh_terms: D000328:Adult; D000068180:Aripiprazole; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009459:Neuroleptic Malignant Syndrome / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D015363:Quinolones / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D012565:Schizophrenic Psychology
chemical_list: D010879:Piperazines; D015363:Quinolones; D005473:Fluoxetine; D000068180:Aripiprazole; D003402:Creatine Kinase; D003024:Clozapine
keywords: aripiprazole; atypical NMS; case series; clozapine; combination therapy; drug-drug interaction; massive creatine kinase elevation; neuroleptic malignant syndrome (NMS)