Overcoming the barriers to identifying and managing treatment-resistant schizophrenia and to improving access to clozapine: A narrative review and recommendation for clinical practice.

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations in clozapine utilization across geographic and clinical settings suggest that it could be possible to improve its use. In this narrative review and expert opinion, we summarized information available in the literature on the mechanisms of action, effectiveness, and potential adverse events of clozapine. We identified barriers leading to discouragement in clozapine prescription internationally, and we proposed practical solutions to overcome each barrier. One of the main obstacles identified to the use of clozapine is the lack of appropriate training for physicians: we highlighted the need to develop specific professional programs to train clinicians, both practicing and in residency, on the relevance and efficacy of clozapine in TRS treatment, initiation, maintenance, and management of potential adverse events. This approach would facilitate physicians to identify eligible patients and offer clozapine as a treatment option in the early stage of the disease. We also noted that increasing awareness of the benefits of clozapine among healthcare professionals, people with TRS, and their caregivers can help promote the use of clozapine. Educational material, such as leaflets or videos, could be developed and distributed to achieve this goal. The information provided in this article may be useful to improve disease burden and support healthcare professionals, patients, and caregivers navigating the complex pathways to TRS management.

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Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest BCF declares that has received speaking honoraria (advisory board and educational lectures) and travel expenses from Rovi, Takeda, Menarini, Angelini, Teva, Otsuka, Lundbeck, Boehringer-Ingelheim and Johnson and Johnson. BC-F has also received fundings to support independent research initiatives (i.e., investigator initiated trials) from Lundbeck and also declares that has received funds from Viatris to conduct this study. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Car dio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Tolmar, Vertex, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. ODH has received investigator-initiated research funding from and/or participated in advisory/ speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Jansenn, Karuna, Lundbeck, Merck, Neurocrine, Ontrack/ Pangea, Otsuka, Sunovion, Recordati, Roche, Rovi and Viatris/ Mylan. He was previously a part-time employee of Lundbeck A/v. Dr Howes has a patent for the use of dopaminergic imaging. NS is a part time medical consultant for Viatris, Finland. He is also a Medical Advisor for Janssen-Cilag, Finland and Recordati, Sweden, and received lecture fees from Viatris, Finland; Otsuka, Finland. ADB has received unrestricted research support from Janssen, Lundbeck, and Otsuka and lecture honoraria for unrestricted educational meeting from Janssen, Chiesi, Lundbeck, Roche, Sunovion, Mylan, Viatris, Recordati, Angelini and Takeda; he has served on advisory boards for Eli Lilly, Jansen, Lundbeck, Otsuka, Roche, and Takeda, Chiesi, Recordati, Angelini, Viatris, Iqvia, Idorsia. OA acts as advisor and consultant for Janssen-Ortho (Johnson & Johnson); Otsuka; Lundbeck; Allergan/Abbvie; Mylan/Viatris; Teva; he is involved in speaking engagements for Janssen-Ortho (Johnson & Johnson); Lundbeck, Otsuka, Mylan/Viatris; HLS Therapeutics; Allergan/Abbvie; he holds research contracts with Janssen-Ortho (Johnson & Johnson); Lundbeck; Otsuka; Boehringer Ingelheim. AF is a consultant and/or speaker and/or has received research grants from Angelini, Apsen, Biogen, Boheringer Ingelheim, Idorsia Italfarmaco, Lundbeck, Janssen, Medicamenta, Mylan, Otsuka, Pfizer, Recordati, Sunovion, Viatris.