Janet Sultana1,2, Andrea Fontana3, Francesco Giorgianni1, Alessandro Pasqua4, Claudio Cricelli4, Edoardo Spina1, Giovanni Gambassi5, Jelena Ivanovic6, Carmen Ferrajolo7,2, Mariam Molokhia8, Clive Ballard9, Samantha Sharp9, Miriam Sturkenboom2, Gianluca Trifirò10,11,12. 1. Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125, Messina, Sicily, Italy. 2. Department of Epidemiology, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. 3. Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Bari, Italy. 4. Health Search, Italian College of General Practitioners, Via Sestese, 61, 50141, Florence, Italy. 5. Department of Internal Medicine, Catholic University of the Sacred Heart, 00168, Rome, Italy. 6. Italian Drug Agency (AIFA), 181 Via del Tritone, 00187, Rome, Italy. 7. Department of Experimental Medicine, Pharmacology section, Campania Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Second University of Naples, 7 Via L. De Crecchio, 80138, Naples, Italy. 8. Department of Primary Care and Public Health Sciences, King's College, London Capital House, 42 Weston Street, London, UK. 9. Biomedical Research Unit for Dementia, Institute of Psychiatry Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK. 10. Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125, Messina, Sicily, Italy. trifirog@unime.it. 11. Department of Epidemiology, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. trifirog@unime.it. 12. IRCCS Centro Neurolesi Bonino Pulejo, Contrada Casazza, SS113, 98124, Messina, Sicily, Italy. trifirog@unime.it.
Abstract
BACKGROUND: Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009. OBJECTIVE: The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy. METHODS: We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65 years and used generalized linear models to explore the effect of the safety warnings. RESULTS: We identified 58,497 and 10,857 individuals aged ≥65 years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3 %, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14 %, respectively). CONCLUSION: The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.
BACKGROUND: Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009. OBJECTIVE: The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy. METHODS: We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65 years and used generalized linear models to explore the effect of the safety warnings. RESULTS: We identified 58,497 and 10,857 individuals aged ≥65 years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3 %, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14 %, respectively). CONCLUSION: The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.
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