An international research agenda for clozapine-resistant schizophrenia

Jurjen J. Luykx*, Jairo M. Gonzalez-Diaz, Ta-Wei Guu, Marte Z. van der Horst, Edwin van Dellen, Marco P. Boks, Sinan Guloksuz, Lynn E. DeLisi, Iris E. Sommer, Russel Cummins, David Shiers, Jimmy Lee, Susanna Every-Palmer, Ahmed Mhalla, Zohra Chadly, Sherry K.W. Chan, Robert O. Cotes, Shun Takahashi, Michael E. Benros, Elias WagnerChristoph U. Correll, Alkomiet Hasan, Dan Siskind, Dominique Endres, James MacCabe, Jari Tiihonen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research avenues to optimise the early detection, diagnosis, and management of clozapine-resistant schizophrenia is unavailable. In this Health Policy, we discuss the ongoing challenges associated with clozapine-resistant schizophrenia faced by patients and health-care providers worldwide to improve the understanding of this condition. We then revisit several clozapine guidelines, the diagnostic tests and treatment options for clozapine-resistant schizophrenia, and currently applied research approaches in clozapine-resistant schizophrenia. We also suggest methodologies and targets for future research, divided into innovative nosology-oriented field trials (eg, examining dimensional symptom staging), translational approaches (eg, genetics), epidemiological research (eg, real-world studies), and interventional studies (eg, non-traditional trial designs incorporating lived experiences and caregivers' perspectives). Finally, we note that low-income and middle-income countries are under-represented in studies on clozapine-resistant schizophrenia and propose an agenda to guide multinational research on the cause and treatment of clozapine-resistant schizophrenia. We hope that this research agenda will empower better global representation of patients living with clozapine-resistant schizophrenia and ultimately improve their functional outcomes and quality of life.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalThe Lancet Psychiatry
Issue number8
Early online date14 Jun 2023
Publication statusPublished - Aug 2023


Dive into the research topics of 'An international research agenda for clozapine-resistant schizophrenia'. Together they form a unique fingerprint.

Cite this