Article
Psychiatry
Shushan Zheng, Sherry Kit Wa Chan, Jimmy Lee
Summary: This study surveyed psychiatrists in Hong Kong and Singapore to understand their familiarity and prescribing practices in treatment-resistant schizophrenia and clozapine-resistant schizophrenia. The results showed that, despite the familiarity with treatment guidelines, delays in prescribing clozapine still occur. The study also found regional differences in alternative treatment methods to clozapine.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Psychiatry
Elias Wagner, Dan Siskind, Peter Falkai, Oliver Howes, Christoph Correll, Jimmy Lee, William G. Honer, John M. Kane, Emilio Fernandez-Egea, Thomas R. E. Barnes, Alkomiet Hasan
Summary: This study conducted an online Delphi survey to develop consensus recommendations for the optimization of clozapine monotherapy. The recommendations include specific treatment options for certain symptoms and management of side effects. The study results provide guidance for clinical decision-making and future research in treatment-resistant schizophrenia.
SCHIZOPHRENIA BULLETIN
(2023)
Article
Psychiatry
Julia M. Lappin, Kimberley Davies, Maryanne O'Donnell, Ishan C. Walpola
Summary: This study aimed to understand the use of clozapine and electroconvulsive therapy (ECT) in individuals with treatment-resistant psychosis. The study found that the utilization of these treatments was low and clozapine trials were often terminated prematurely without adequate testing. The study suggests strategies should be implemented to optimize the use of clozapine therapy and ECT in clinical settings to improve the therapeutic effectiveness for treatment-resistant psychosis.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Psychiatry
Can Ugurpala, Ertug Berberoglu, Utku Ozkan, Selin Akisk Genc, Nuran Caglar Tanriverdi, Damla Inhanli, Chouda Ali, Alp Ucok
Summary: This study investigates the relationship between minor physical anomalies (MPA) and treatment resistance in schizophrenia (TRS). It found that TRS patients had higher total MPA score, and MPAs in the eye and mouth regions were more frequent in TRS patients compared to non-TRS patients. The total MPA score was correlated to BPRS-E total and BPRS positive scores in TRS patients. These findings suggest that MPA might contribute to treatment resistance in schizophrenia.
ASIAN JOURNAL OF PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Elias D. Mouchlianitis, Lucy D. Vanes, Derek K. Tracy, Anne-Katherin Fett, Daniel Joyce, Sukhi S. Shergill
Summary: Glutamatergic dysfunction is associated with treatment resistance in individuals with schizophrenia. This study used neurochemical and functional brain imaging methods to investigate glutamatergic dysfunction and reward processing in treatment-resistant and treatment-responsive schizophrenia. The results suggest that glutamatergic differences can differentiate treatment-resistant and treatment-responsive schizophrenia, which has potential diagnostic value.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Alejandra Zazueta, Tito Castillo, Alvaro Cavieres, Rene Gonzalez, Maximiliano Abarca, Rodrigo R. Nieto, Javier Deneken, Cristian Araneda, Pablo R. Moya, M. Leonor Bustamante
Summary: The response to conventional antipsychotic drugs and clozapine treatment is associated with genetic variations, but more research is needed for personalized prescriptions.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Ming-Huan Zhu, Zhen-Jing Liu, Qiong-Yue Hu, Jia-Yu Yang, Ying Jin, Na Zhu, Ying Huang, Dian-Hong Shi, Min-Jia Liu, Hong-Yang Tan, Lei Zhao, Qin-Yu Lv, Zheng-Hui Yi, Feng-Chun Wu, Ze-Zhi Li
Summary: This study aimed to investigate the efficacy of amisulpride augmentation therapy in treating patients with treatment-resistant schizophrenia. The results showed that amisulpride augmentation therapy improved psychiatric symptoms and cognitive function with tolerability and safety.
MILITARY MEDICAL RESEARCH
(2022)
Article
Psychiatry
Laura Orsolini, Silvia Bellagamba, Virginio Salvi, Umberto Volpe
Summary: This article describes a 20-year-old patient with clozapine-resistant schizophrenia and comorbid cannabinoid use disorder, who was successfully treated with a combination of clozapine and brexpiprazole, and later switched to clozapine with long-acting injectable aripiprazole.
ASIAN JOURNAL OF PSYCHIATRY
(2022)
Article
Psychiatry
Simon S. Y. Lui, Stanley S. L. Yip, Ya Wang, Karen S. Y. Hung, Karen K. Y. Ho, Kirby C. M. Tsang, Hera K. H. Yeung, Eric F. C. Cheung, Raymond C. K. Chan
Summary: The study investigated the trajectory of neurological soft signs (NSS) in schizophrenia patients and found that NSS worsened over time in treatment-resistant patients. This suggests that NSS may be useful in identifying treatment resistance in first-episode schizophrenia patients, reflecting the development of underlying neuropathology.
JOURNAL OF PSYCHIATRIC RESEARCH
(2021)
Review
Psychiatry
Mattia Campana, Peter Falkai, Dan Siskind, Alkomiet Hasan, Elias Wagner
Summary: This systematic review and meta-analysis aimed to characterize ultra-treatment-resistant Schizophrenia patients and investigate the consistency in CRS definitions between studies. The results showed a large heterogeneity of CRS definitions and insufficient guidelines implementation. A new score modeled on a best practice definition was offered to help future trials increase their reliability.
SCHIZOPHRENIA RESEARCH
(2021)
Article
Clinical Neurology
Chuanjun Zhuo, Yong Xu, Haibo Wang, Chunhua Zhou, Jian Liu, Xiaocui Yu, Hailin Shao, Hongjun Tian, Tao Fang, Qianchen Li, Jiayue Chen, Shuli Xu, Xiaoyan Ma, Weiliang Yang, Cong Yao, Bo Li, Anqu Yang, Yuhui Chen, Guoyong Huang, Chongguang Lin
Summary: Clozapine-induced metformin-resistant prediabetes/diabetes is common in the early-treatment resistance subtype of treatment-resistant schizophrenia and is associated with poor clinical efficacy of clozapine.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Editorial Material
Psychiatry
Rodolfo Furlan Damiano, Belquiz S. Avrichir, Debora L. Melzer-Ribeiro, Paulo Clemente Sallet, Helio Elkis
Summary: This is a case report of a patient with treatment-resistant schizophrenia who has failed to respond to clozapine and electroconvulsive therapy, and has a history of multiple suicide attempts. Evidence-based clinical decisions for managing such patients were discussed.
PSYCHIATRY RESEARCH
(2021)
Article
Psychology, Clinical
Jerome Brunelin, Filipe Galvao, Marine Mondino
Summary: This retrospective study investigated the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant auditory verbal hallucinations. The results showed that low frequency rTMS could significantly decrease these symptoms.
INTERNATIONAL JOURNAL OF CLINICAL AND HEALTH PSYCHOLOGY
(2023)
Article
Psychiatry
Amina Aissa, Rahma Jouini, Uta Ouali, Yosra Zgueb, Fethi Nacef, Zouhaier El Hechmi
Summary: The study aims to investigate demographic, clinical, and biochemical patient characteristics as potential predictors of response to clozapine in patients with Treatment Resistant Schizophrenia (TRS). Results showed that patients with better premorbid social functioning in childhood and early adolescence tend to have a better response to clozapine. Additionally, a shorter delay in clozapine initiation, having tried at least one atypical antipsychotic, and having schizophrenia paranoid subtype were significantly predictive of a good response to clozapine.
COMPREHENSIVE PSYCHIATRY
(2022)
Article
Psychiatry
Graham Blackman, Ebenezer Oloyede, Mark Horowitz, Robert Harland, David Taylor, James MacCabe, Philip McGuire
Summary: There is currently no formal guidance on how to safely discontinue clozapine treatment, which poses risks of psychotic relapse and withdrawal symptoms.
SCHIZOPHRENIA BULLETIN
(2022)
Article
Psychiatry
Graham Blackman, Ebenezer Oloyede, Mark Horowitz, Robert Harland, David Taylor, James MacCabe, Philip McGuire
Summary: There is currently no formal guidance on how to safely discontinue clozapine treatment, which poses risks of psychotic relapse and withdrawal symptoms.
SCHIZOPHRENIA BULLETIN
(2022)
Article
Psychiatry
Antonio F. Pardinas, Sophie E. Smart, Isabella R. Willcocks, Peter A. Holmans, Charlotte A. Dennison, Amy J. Lynham, Sophie E. Legge, Bernhard T. Baune, Tim B. Bigdeli, Murray J. Cairns, Aiden Corvin, Ayman H. Fanous, Josef Frank, Brian Kelly, Andrew McQuillin, Ingrid Melle, Preben B. Mortensen, Bryan J. Mowry, Carlos N. Pato, Sathish Periyasamy, Marcella Rietschel, Dan Rujescu, Carmen Simonsen, David St Clair, Paul Tooney, Jing Qin Wu, Ole A. Andreassen, Kaarina Kowalec, Patrick F. Sullivan, Robin M. Murray, Michael J. Owen, James H. MacCabe, Michael C. O'Donovan, James T. R. Walters
Summary: This study examined the genetic architecture of treatment-resistant schizophrenia (TRS) by reassessing genetic data from schizophrenia studies and validating it in carefully ascertained clinical samples. The results showed that TRS is a polygenic trait with detectable heritability, and it is genetically correlated with traits related to intelligence and cognition. The study also found associations between TRS and a history of taking clozapine.
Article
Psychiatry
Emma Butler, Toby Pillinger, Kirsten Brown, Faith Borgan, Alice Bowen, Katherine Beck, Enrico D'Ambrosio, Lisa Donaldson, Sameer Jauhar, Stephen Kaar, Tiago Reis Marques, Robert A. McCutcheon, Maria Rogdaki, Fiona Gaughran, James MacCabe, Rosalind Ramsay, David Taylor, Paul McCrone, Alice Egerton, Oliver D. Howes
Summary: This study demonstrates the feasibility of community initiation of clozapine for treatment-resistant schizophrenia. It is associated with significant reductions in costs, service use, and symptom severity.
BRITISH JOURNAL OF PSYCHIATRY
(2022)
Article
Clinical Neurology
Risha Govind, Daniela Fonseca de Freitas, Megan Pritchard, Mizanur Khondoker, James T. Teo, Robert Stewart, Richard D. Hayes, James H. MacCabe
Summary: This study investigated the association between clozapine treatment and increased risk of adverse outcomes in COVID-19 among patients with schizophrenia-spectrum disorders. The results showed that there was no significant association between clozapine treatment and hospitalization, intensive care treatment, or death during COVID-19 infection.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
Daniela Fonseca de Freitas, Giouliana Kadra-Scalzo, Deborah Agbedjro, Emma Francis, Isobel Ridler, Megan Pritchard, Hitesh Shetty, Aviv Segev, Cecilia Casetta, Sophie E. Smart, Johnny Downs, Soren Rahn Christensen, Nikolaj Bak, Bruce J. Kinon, Daniel Stahl, James H. MacCabe, Richard D. Hayes
Summary: In the treatment of treatment-resistant schizophrenia, some patients do not show improvement with clozapine treatment. This study found that patients with higher baseline illness severity, female gender, and comorbid mood disorders have a better response to clozapine.
JOURNAL OF PSYCHOPHARMACOLOGY
(2022)
Article
Psychiatry
Daniela Fonseca de Freitas, India Patel, Giouliana Kadra-Scalzo, Megan Pritchard, Hitesh Shetty, Matthew Broadbent, Rashmi Patel, Johnny Downs, Aviv Segev, Mizanur Khondoker, James H. MacCabe, Kamaldeep Bhui, Richard D. Hayes
Summary: This study investigates the ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder, and finds that black service-users are less likely to receive clozapine compared to white British service-users.
SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
(2022)
Article
Psychiatry
Fanni Krajner, Laila Hadaya, Grant McQueen, Kyra-Verena Sendt, Amy Gillespie, Alessia Avila, John Lally, Emily P. Hedges, Kelly Diederen, Oliver D. Howes, Gareth J. Barker, David J. Lythgoe, Matthew J. Kempton, Philip McGuire, James H. MacCabe, Alice Egerton
Summary: The neurobiological effects of clozapine treatment on subcortical volume and cortical thickness were investigated. The results showed reductions in the volumes of caudate and putamen, enlargement of the lateral ventricles, and reductions in the thickness of specific cortical regions. The reduction in right caudate volume was associated with local reductions in NAA. No association was found between these morphometric changes and glutamate levels.
Article
Psychiatry
Ebenezer Oloyede, Olubanke Dzahini, Zadro Abolou, Siobhan Gee, Eromona Whiskey, Diksha Malhotra, Masuma Hussain, Ian Osborne, Cecilia Casetta, Philip McGuire, James H. H. MacCabe, David Taylor
Summary: To minimize infection during COVID-19, the clozapine hematalogical monitoring interval was extended. This study aims to investigate the impact of this temporary policy change on clinical and safety outcomes.
BRITISH JOURNAL OF PSYCHIATRY
(2023)
Article
Endocrinology & Metabolism
Giovanna Nordio, Rubaida Easmin, Alessio Giacomel, Ottavia Dipasquale, Daniel Martins, Steven Williams, Federico Turkheimer, Oliver Howes, Mattia Veronese, Sameer Jauhar, Maria Rogdaki, Robert McCutcheon, Stephen Kaar, Luke Vano, Grazia Rutigliano, Ilinca Angelescu, Faith Borgan, Enrico D'Ambrosio, Tarik Dahoun, Euitae Kim, Seoyoung Kim, Micheal Bloomfield, Alice Egerton, Arsime Demjaha, Ilaria Bonoldi, Chiara Nosarti, James Maccabe, Philip McGuire, Julian Matthews, Peter S. Talbot
Summary: In this study, a fully automated analytical framework for FDOPA PET neuroimaging data was evaluated. The framework showed good reproducibility and sensitivity to demographic and experimental variables. It represents an effective resource for standardized and robust quantification of dopamine synthesis capacity using FDOPA PET data.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Psychiatry
Edward Millgate, Sophie E. Smart, Antonio F. Pardinas, Eugenia Kravariti, Olesya Ajnakina, Adrianna P. Kapinska, Ole A. Andreassen, Thomas R. E. Barnes, Domenico Berardi, Benedicto Crespo-Facorro, Giuseppe D'Andre, Arsime Demjaha, Marta Di Forti, Gillian A. Doody, Laura Kassoumeri, Aziz Ferchiou, Lorenzo Guidi, Eileen M. Joyce, Ornella Lastrina, Ingrid Melle, Baptiste Pignon, Jean-Romain Richard, Carmen Simonsen, Andrei Szoke, Ilaria Tarricone, Andrea Tortelli, Javier Vazquez-Bourgon, Robin M. Murray, James T. R. Walters, James H. MacCabe
Summary: This study aimed to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases. The findings showed that patients who were future classified as treatment resistant reported poorer performance across most cognitive domains at baseline. These results indicate that deficits in IQ/general cognitive functioning at first episode are associated with future treatment resistance.
SCHIZOPHRENIA RESEARCH
(2023)
Editorial Material
Psychiatry
Ebenezer Oloyede, David Taylor, James MacCabe
Summary: The Viewpoint discusses the differences in stringency of hematologic monitoring for clozapine across countries and proposes approaches for monitoring.
Article
Psychiatry
Ebenezer Oloyede, Graham Blackman, Bethany Mantell, Eleanor Harris, Julie Williams, David Taylor, James MacCabe, Philip McGuire
Summary: The study finds that there is significant underuse of clozapine in early intervention psychosis services, mainly due to patient concerns about side effects, monitoring requirements, as well as clinician concerns. To improve the utilization of clozapine, greater training for clinicians, improved resources, and optimized monitoring are needed.
Meeting Abstract
Psychiatry
D. Fonseca De Freitas, I. Patel, G. Kadra-Scalzo, M. Pritchard, H. Shetty, M. Broadbent, R. Patel, J. Downs, A. Segev, M. Khondoker, J. Maccabe, K. Bhui, R. Hayes
EUROPEAN PSYCHIATRY
(2022)
Meeting Abstract
Psychiatry
D. Fonseca De Freitas, D. Agbedjro, G. Kadra-Scalzo, E. Francis, I. Ridler, M. Pritchard, H. Shetty, A. Segev, C. Casetta, S. Smart, A. Morris, J. Downs, S. Christensen, N. Bak, B. Kinon, D. Stahl, R. Hayes, J. Maccabe
EUROPEAN PSYCHIATRY
(2022)
Article
Psychiatry
Kira Griffiths, Alice Egerton, Edward Millgate, Adriana Anton, Gareth J. Barker, Bill Deakin, Richard Drake, Emma Eliasson, Catherine J. Gregory, Oliver D. Howes, Eugenia Kravariti, Stephen M. Lawrie, Shon Lewis, David J. Lythgoe, Anna Murphy, Philip McGuire, Scott Semple, Charlotte Stockton-Powdrell, James T. R. Walters, Stephen R. Williams, James H. MacCabe
Summary: In this study, the relationship between brain glutamate levels and cognitive abilities in patients with schizophrenia was investigated using proton magnetic resonance spectroscopy. The results showed that lower levels of glutamate in the anterior cingulate cortex were associated with worse verbal memory. This relationship was independent of the response to antipsychotic medication.