Unresolved issues for utilization of atypical antipsychotics in schizophrenia: Antipsychotic polypharmacy and metabolic syndrome

Sang Won Jeon, Yong Ku Kim

Research output: Contribution to journalReview articlepeer-review

58 Citations (Scopus)


Atypical antipsychotics (AAP) are the prevailing form of schizophrenia treatment today due to their low side effects and superior efficacy. Nevertheless, some issues still need to be addressed. First, there are still a large number of patients with treatment-resistant schizophrenia (TRS), which has led to a growing trend to resort to AAP polypharmacy with few side effects. Most clinical treatment guidelines recommend clozapine monotherapy in TRS, but around one third of schizophrenic patients fail to respond to clozapine. For these patients, with clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a continually growing evidence base. Second, AAP generally have great risks for developing metabolic syndrome, such as weight gain, abnormality in glucose, and lipid metabolism. These metabolic side effects have become huge stumbling blocks in today’s schizophrenia treatment that aims to improve patients’ quality of life as well as symptoms. The exact reasons why this particular syndrome occurs in patients treated with AAP is as yet unclear though factors such as interaction of AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length of AAP use, and life style of schizophrenic patients that may contribute to its development. The present article aimed to review the evidence underlying these key issues and provide the most reasonable interpretations to expand the overall scope of antipsychotics usage.

Original languageEnglish
Article number2174
JournalInternational journal of molecular sciences
Issue number10
Publication statusPublished - 2017 Oct 18
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.


  • Atypical antipsychotics
  • Metabolic syndrome
  • Polypharmacy
  • Schizophrenia
  • Treatment resistance

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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