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The Effect of Safety Warnings on Antipsychotic Drug Prescribing in Elderly Persons with Dementia in the United Kingdom and Italy: A Population-Based Study

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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.

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Author Contributions

The authors contributed to the present study as follows. Literature search: JS, JI, CB, SS; study design/writing of protocol: JS, AF, GT; data extraction/data management: JS, FG, AP; data analysis: AF, JS, FG; writing and revision of manuscript: JS, AF, FG, AP, CB, CC, SS, ES, GG, JI, CF, MM, MS, GT; conception of study: GT. GT has access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125, Messina, Sicily, Italy

    Janet Sultana, Francesco Giorgianni, Edoardo Spina & Gianluca Trifirò

  2. Unit of Biostatistics, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Bari, Italy

    Andrea Fontana

  3. Health Search, Italian College of General Practitioners, Via Sestese, 61, 50141, Florence, Italy

    Alessandro Pasqua & Claudio Cricelli

  4. Department of Internal Medicine, Catholic University of the Sacred Heart, 00168, Rome, Italy

    Giovanni Gambassi

  5. Italian Drug Agency (AIFA), 181 Via del Tritone, 00187, Rome, Italy

    Jelena Ivanovic

  6. 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

    Carmen Ferrajolo

  7. Department of Epidemiology, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands

    Janet Sultana, Carmen Ferrajolo, Miriam Sturkenboom & Gianluca Trifirò

  8. Department of Primary Care and Public Health Sciences, King’s College, London Capital House, 42 Weston Street, London, UK

    Mariam Molokhia

  9. Biomedical Research Unit for Dementia, Institute of Psychiatry Psychology and Neuroscience, King’s College London, De Crespigny Park, London, UK

    Clive Ballard & Samantha Sharp

  10. IRCCS Centro Neurolesi Bonino Pulejo, Contrada Casazza, SS113, 98124, Messina, Sicily, Italy

    Gianluca Trifirò

Authors
  1. Janet Sultana
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  2. Andrea Fontana
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  3. Francesco Giorgianni
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  4. Alessandro Pasqua
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  6. Edoardo Spina
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  7. Giovanni Gambassi
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  8. Jelena Ivanovic
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  9. Carmen Ferrajolo
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  10. Mariam Molokhia
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  11. Clive Ballard
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  12. Samantha Sharp
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  13. Miriam Sturkenboom
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  14. Gianluca Trifirò
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Corresponding author

Correspondence to Gianluca Trifirò.

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Funding

This study was funded by the Italian Health Minister in the context of the Project “GR-2009-1607316—Assessment of the Safety of Antipsychotic Drugs in Elderly with Dementia: An International, Population-Based Study Using Healthcare Databases”. The funder played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Conflicts of interest

JS, AF, FG, AP, CB, CC, SS, ES, GG, JI, CF, MM, MS and GT have no competing interests to declare directly related to the present study. CC has received consulting fees/honoraria from Bayer unrelated to this study. ES has received grants unrelated to this study, consulting fees/honoraria from Eli Lilly unrelated to this study, payment for lectures unrelated to the study and is a board member for Astra-Zeneca and Lundbeck. MM has received funding from Pfizer, Astra-Zeneca and the international Adverse Events Consortium for studies unrelated to this study. CB has received grants and personal fees from Arcadia, Lundbeck, Napp, Roche, Orion, Bial, Bristol Myer Squibb, Otusaka and Novartis unrelated to this study.

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Sultana, J., Fontana, A., Giorgianni, F. et al. The Effect of Safety Warnings on Antipsychotic Drug Prescribing in Elderly Persons with Dementia in the United Kingdom and Italy: A Population-Based Study. CNS Drugs 30, 1097–1109 (2016). https://doi.org/10.1007/s40263-016-0366-z

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