| アブストラクト | BACKGROUND: Antipsychotic use in people living with dementia has been linked to serious adverse outcomes. Guidelines recommend limiting antipsychotic treatment to short-term use (<12 weeks), followed by tapering and cessation. However, antipsychotic treatment in routine practice often exceeds the recommended duration. The effect of discontinuing antipsychotics on reducing adverse outcomes in practice remains unclear. We aimed to use linked primary and secondary care data in England to investigate whether tapering or abrupt discontinuation of antipsychotics, versus continuation, affected the risk of stroke, death, fracture, delirium, and pneumonia in people living with dementia. METHODS: Using UK primary care data from the Clinical Practice Research Datalink, linked with hospital and mortality data from Jan 1, 1998, to March 31, 2021, we emulated two sets of target trials, one after 12 weeks of antipsychotic treatment and another after 24 weeks of antipsychotic treatment, to compare continuing treatment versus tapering treatment and continuing treatment versus abrupt discontinuation of treatment. Patients aged 65 years and older at incident dementia diagnosis with antipsychotic treatment duration of at least 12 weeks were included. Study outcomes were incidence of fracture, stroke, hospitalisation for delirium, hospitalisation for pneumonia, and all-cause mortality within 24 months. A negative control outcome of skin conditions was included to measure potential unmeasured confounding. A clone-censor-weight approach was used with a 6-month grace period allowed for discontinuing antipsychotics. Weighted pooled logistic regression models were used to estimate 24-month absolute risk differences (ARDs). FINDINGS: 134 549 eligible patients had a new antipsychotic treatment after dementia diagnosis, of whom 24 822 (18.4%) had a treatment period of at least 12 weeks and 16 795 (12.5%) had a treatment period of at least 24 weeks and met the eligibility criteria. The mean age was 83.57 (SD 7.07) in the 12-week trial and 83.65 (SD 7.02) in the 24-week trial; 16 725 (67.4%) of 24 822 patients were female and 8097 were male in the 12-week trial and 11 523 (68.6%) of 16 795 patients were female and 5272 were male in the 24-week trial. Compared with continuation after 12 weeks of treatment, estimated risks of delirium and fracture under the tapering strategy corresponded to 24-month ARDs of -2.46% (95% CI -4.10 to -1.27) and -2.80% (-4.14 to -1.29), respectively. Estimated risks for stroke, pneumonia, and all-cause mortality were similar between strategies. No difference in risk was observed for the negative control outcome. Similar results were found after 24 weeks of treatment and in sensitivity analyses. INTERPRETATION: Irrespective of method, antipsychotic discontinuation decreased the risk of delirium and fracture. Antipsychotics can be discontinued safely when treatment duration has exceeded guideline recommendations without increasing the risk of death, stroke, or pneumonia in those living with dementia. FUNDING: PharmAlliance Research Clusters for Doctoral Training. |
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| ジャーナル名 | The lancet. Healthy longevity |
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| Pubmed追加日 | 2026/6/17 |
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| 投稿者 | Hopkinson, Olivia K; Chobanov, Jan; Goordeen, Darshna; Man, Kenneth K C; Wong, Ian C K; Reeve, Emily; Bell, J Simon; Wei, Li; Howard, Robert; Lau, Wallis C Y |
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| 組織名 | Research Department of Practice and Policy, School of Pharmacy, University;College London, London, UK.;Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical;Sciences, Monash University, Melbourne, VIC, Australia.;College London, London, UK; Centre for Medicines Optimisation Research and;Education, University College London Hospitals NHS Foundation Trust, London, UK;;Centre for Safe Medication Practice and Research, Department of Pharmacology and;Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong;Special Administrative Region, China; Laboratory of Data Discovery for Health;(D(2)4H), Hong Kong Special Administrative Region, China.;(D(2)4H), Hong Kong Special Administrative Region, China; School of Pharmacy,;Aston University, Birmingham, UK.;Sciences, Monash University, Melbourne, VIC, Australia; School of Pharmacy and;Biomedical Science, Adelaide University, Adelaide, SA, Australia.;Education, University College London Hospitals NHS Foundation Trust, London, UK.;Division of Psychiatry, University College London, London, UK.;(D(2)4H), Hong Kong Special Administrative Region, China. Electronic address:;wallis.lau@ucl.ac.uk. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42302797/ |
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