JOP0010.1177/0269881119889296Journal of PsychopharmacologyBarnes et al. 889296review-article2019 BAP Guidelines Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Journal of Psychopharmacology 1 –76 Association for Psychopharmacology © The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI:https://doi.org/10.1177/0269881119889296 10.1177/0269881119889296 journals.sagepub.com/home/jop Thomas RE Barnes1 , Richard Drake2, Carol Paton3 , Stephen J Cooper4, Bill Deakin5, I Nicol Ferrier6, Catherine J Gregory7, Peter M Haddad8, Oliver D Howes9, Ian Jones10, Eileen M Joyce11, Shôn Lewis12, Anne Lingford-Hughes13, James H MacCabe14, David Cunningham Owens15, Maxine X Patel16, Julia MA Sinclair17, James M Stone18 , Peter S Talbot19, Rachel Upthegrove20, Angelika Wieck21 and Alison R Yung22 Abstract These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement. Keywords Guideline, schizophrenia, psychopharmacology 14 Professor of Epidemiology and Therapeutics, Department of Psychosis 1Emeritus Professor of Clinical Psychiatry, Division of Psychiatry, Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s Imperial College London, and Joint-head of the Prescribing College London, and Honorary Consultant Psychiatrist, National Observatory for Mental Health, Centre for Quality Improvement, Royal Psychosis Service, South London and Maudsley NHS Foundation Trust, College of Psychiatrists, London, UK Beckenham, UK 2 Clinical Lead for Mental Health in Working Age Adults, Health 15Professor of Clinical Psychiatry, University of Edinburgh. Honorary Innovation Manchester, University of Manchester and Greater Consultant Psychiatrist, Royal Edinburgh Hospital, Edinburgh, UK Manchester Mental Health NHS Foundation Trust, Manchester, UK 16 Honorary Clinical Senior Lecturer, King’s College London, Institute of 3 Joint-head of the Prescribing Observatory for Mental Health, Centre Psychiatry, Psychology and Neuroscience and Consultant Psychiatrist, for Quality Improvement, Royal College of Psychiatrists, London, UK Oxleas NHS Foundation Trust, London, UK 4 Emeritus Professor of Psychiatry, School of Medicine, Queen’s 17 Professor of Addiction Psychiatry, Faculty of Medicine, University of University Belfast, Belfast, UK Southampton, Southampton, UK 5 Professor of Psychiatry, Neuroscience & Psychiatry Unit, University of 18 Clinical Senior Lecturer and Honorary Consultant Psychiatrist, King’s Manchester and Greater Manchester Mental Health NHS Foundation College London, Institute of Psychiatry, Psychology and Neuroscience Trust, Manchester, UK and South London and Maudsley NHS Trust, London, UK 6Emeritus Professor of Psychiatry, Institute of Neuroscience, Newcastle 19Senior Lecturer and Honorary Consultant Psychiatrist, University of University, Newcastle upon Tyne, UK Manchester and Greater Manchester Mental Health NHS Foundation 7 Honorary Clinical Research Fellow, University of Manchester and Trust, Manchester, UK Higher Trainee in Child and Adolescent Psychiatry, Manchester 20 Professor of Psychiatry and Youth Mental Health, University University NHS Foundation Trust, Manchester, UK of Birmingham and Consultant Psychiatrist, Birmingham Early 8 Honorary Professor of Psychiatry, Division of Psychology and Mental Intervention Service, Birmingham Women’s and Children’s NHS Health, University of Manchester, UK and Senior Consultant Psychiatrist, Foundation Trust, Birmingham, UK Department of Psychiatry, Hamad Medical Corporation, Doha, Qatar 21 Honorary Consultant in Perinatal Psychiatry, Greater Manchester 9 Professor of Molecular Psychiatry, Imperial College London and Mental Health NHS Foundation Trust, Manchester, UK Institute of Psychiatry, Psychology and Neuroscience, King’s College 22 Professor of Psychiatry, University of Manchester, School of Health London, London, UK Sciences, Manchester, UK and Centre for Youth Mental Health, 10Professor of Psychiatry and Director, National Centre of Mental University of Melbourne, Australia, and Honorary Consultant Health, Cardiff University, Cardiff, UK Psychiatrist, Greater Manchester Mental Health NHS Foundation Trust, 11Professor of Neuropsychiatry, UCL Queen Square Institute of Manchester, UK Neurology, London, UK 12Professor of Adult Psychiatry, Faculty of Biology, Medicine and Corresponding author: Health, The University of Manchester, UK, and Mental Health Thomas R E Barnes, Emeritus Professor of Clinical Psychiatry, Academic Lead, Health Innovation Manchester, Manchester, UK Division of Psychiatry, Imperial College London, Du Cane Road, 13 Professor of Addiction Biology and Honorary Consultant Psychiatrist, London, W12 0NN, UK. Imperial College London and Central North West London NHS Email: [email protected] Foundation Trust, London, UK 2 Journal of Psychopharmacology 00(0) Introduction IIb: evidence from pharmacovigilance studies III: evidence from non-representative surveys, case reports The methodology for this updated guideline was essentially the IV: evidence from expert committee reports or opinions and/ same as was followed for previous British Association for or clinical experience of respected authorities Psychopharmacology (BAP) guidelines. A meeting of experts was convened in May 2017 with a remit to produce up-to-date, evi- Strength of recommendation dence-based, consensus recommendations covering the pharmaco- logical management of schizophrenia from first episode to A: directly based on category I evidence long-term relapse prevention, targeting treatment for particular per- B: directly based on category II evidence or extrapolated sistent symptoms, and strategies for refractory illness. All the con- recommendation from category I evidence tributors invited to the meeting had extensive clinical experience of C: directly based on category III evidence or extrapolated the treatment of people with schizophrenia and each of them gave a recommendation from category I or II evidence brief presentation of the published evidence relevant to the section D: directly based on category IV evidence or extrapolated of the guideline they would write. The costs of the meeting were recommendation from category I, II or III evidence defrayed by the BAP. Subsequently, the submissions from each of the co-authors were edited and integrated into a first draft which The recommendations are graded A to D, as shown above. We dis- was then circulated for further amendment and updating in 2018. A tinguish between the category of evidence and the strength of the second draft was similarly revised and updated in 2019. associated recommendation. It is possible to have methodologi- cally sound (category I) evidence about an area of practice that is clinically irrelevant or where the effect is modest and of little prac- Strength of evidence and recommendations tical significance and therefore a lower strength of recommenda- for guidelines tion is warranted. More commonly, a statement of evidence covers only one aspect of a recommendation or covers it in a way that To rank the evidence and the strength of recommendations, the conflicts with other evidence. Therefore, to produce comprehen- authors followed the categories used in the earlier, published ver- sive recommendations it is necessary to generalise from the avail- sion of this guideline (Barnes et al., 2011), which had been taken able evidence. This may lead to weaker levels of recommendation from the methodology of the North of England Evidence-Based (B, C or D) based upon category I evidence statements. Guideline Development Project, developed by the Centre for Deriving realistic, sound recommendations for clinical practice Health Services Research, University of Newcastle upon Tyne from a disparate and inconsistent evidence base is not straightfor- and the Centre for Health Economics, University of York. ward; it is not simply the application of deductive reasoning or sim- ple extrapolation. Critical appraisal of research studies and judicious Evidence categories. The six evidence categories (see Shekelle reflection on clinical experience are necessary, as well as some et al., 1999) are as follows: insight into the cognitive biases and defaults involved in the deci- sion-making process. Where recommendations were predominantly Categories of evidence for causal relationships and derived from a consensus view, in the absence of valid, systematic treatment evidence, they are graded as S (standard of good practice). Ia: evidence from meta-analysis of randomised controlled