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, Ahmed Mhalla, Zohra Chadly, Sherry K.W. Chan, Robert O. Cotes, Shun Takahashi, Michael E. Benros, Elias Wagner, Christoph U. Correll, Alkomiet HasanDan Siskind, Dominique Endres, James MacCabe, Jari Tiihonen

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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 (US)
Pages (from-to)644-652
Number of pages9
JournalThe Lancet Psychiatry
Issue number8
StatePublished - Aug 2023

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry


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