Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome

Po Yu Chen, Chin Kuo Chang, Chun Hsin Chen, Su Chen Fang, Valeria Mondelli, Chih Chiang Chiu, Mong Liang Lu, Ling Ling Hwang, Ming Chyi Huang

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background/Purpose: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. Methods: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. Results: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. Conclusion: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

Original languageEnglish
Pages (from-to)2172-2181
Number of pages10
JournalJournal of the Formosan Medical Association
Issue number11
Publication statusAccepted/In press - 2022


  • Antipsychotics
  • Metabolic syndrome
  • Orexin-A
  • Schizophrenia
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • General Medicine


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