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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Associated mortality risk of atypical antipsychotic medication in individuals with dementia
Peter Phiri, Tomas Engelthaler, Hannah Carr, Gayathri Delanerolle, Clive Holmes, Shanaya Rathod
Peter Phiri, Hannah Carr, Shanaya Rathod, Research & Innovation Department, Southern Health NHS Foundation Trust, Southampton SO30 3JB, United Kingdom
Peter Phiri, Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton SO16 5ST, United Kingdom
Tomas Engelthaler, Oxford Centre for Innovation, Akrivia Health, Oxford OX1 BY, United Kingdom
Hannah Carr, Department of Psychology, University of Southampton, Southampton SO16 5ST, United Kingdom
Gayathri Delanerolle, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom
Clive Holmes, Clinical and Experimental Sciences, University of Southampton, Southampton SO16 5ST, United Kingdom
Clive Holmes, Research & Innovation Department, Memory Assessment & Research Centre, Southern Health NHS Foundation Trust, Southampton SO30 3JB, United Kingdom
Author contributions: Phiri P and Carr H drafted the study protocol; Phiri P wrote the first draft of the manuscript version; Engelthaler T conducted the data extraction and analysis; all authors contributed to the critical revision of the manuscript and have approved the final manuscript.
Institutional review board statement: Health Research Authority (HRA) provided guidance to the Akrivia Health and all data controllers that neither ethics nor HRA approval (legal & governance) is required for the establishment of the Clinical Record Interactive Search (CRIS) system or using de-identified data (from the system) for research purposes in March 2020. Local approvals were obtained from the Southern Health NHS Foundation Trust (SHFT) patient-led oversight committee.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: Phiri P has received other, educational from Queen Mary University of London, Stanford University School of Medicine and other from John Wiley and Blackwell, outside the submitted work. Rathod S reports other from Janssen, Otsuka and Lundbeck outside the submitted work. All other authors report no conflict of interest.
Data sharing statement: No additional data available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Peter Phiri, BSc, PhD, RN, Academic Fellow, Research & Innovation Department, Southern Health NHS Foundation Trust, Botley Road, West End, Southampton SO30 3JB, United Kingdom. peter.phiri@southernhealth.nhs.uk
Received: June 28, 2021
Peer-review started: June 28, 2021
First decision: September 5, 2021
Revised: September 24, 2021
Accepted: January 17, 2022
Article in press: January 17, 2022
Published online: February 19, 2022
BACKGROUND
Antipsychotic medications such as risperidone, olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients. Current evidence indicate prescription rates for antipsychotics vary and wider consensus to evaluate clinical epidemiological outcomes is limited.
AIM
To investigate the potential impact of atypical antipsychotics on the mortality of patients with dementia.
METHODS
A retrospective clinical cohort study was developed to review United Kingdom Clinical Record Interactive Search system based data between January 1, 2013 to December 31, 2017. A descriptive statistical method was used to analyse the data. Mini Mental State Examination (MMSE) scores were used to assess the severity and stage of disease progression. A cox proportional hazards model was developed to evaluate the relationship between survival following diagnosis and other variables.
RESULTS
A total of 1692 patients were identified using natural language processing of which, 587 were prescribed olanzapine, quetiapine or risperidone (common group) whilst 893 (control group) were not prescribed any antipsychotics. Patients prescribed olanzapine showed an increased risk of death [hazard ratio (HR) = 1.32; 95% confidence interval (CI): 1.08-1.60; P < 0.01], as did those with risperidone (HR = 1.35; 95%CI: 1.18-1.54; P < 0.001). Patients prescribed quetiapine showed no significant association (HR = 1.09; 95%CI: 0.90-1.34; P = 0.38). Factors associated with a lower risk of death were: High MMSE score at diagnosis (HR = 0.72; 95%CI: 0.62-0.83; P < 0.001), identifying as female (HR = 0.73; 95%CI: 0.64-0.82; P < 0.001), and being of a White-British ethnic group (HR = 0.82; 95%CI: 0.72-0.94; P < 0.01).
CONCLUSION
A significant mortality risk was identified among those prescribed olanzapine and risperidone which contradicts previous findings although the study designs used were different. Comprehensive research should be conducted to better assess clinical epidemiological outcomes associated with diagnosis and therapies to improve clinical management of these patients.
Core Tip: Antipsychotic medication is widely prescribed to patients with dementia displaying neuropsychiatric symptoms. Treatment with olanzapine and risperidone was associated with an increased mortality risk. In comparison, quetiapine showed a relatively lower, non-significant association with the mortality risk in those with dementia. Clinicians need to be aware of the potential heterogeneous relationship between dementias, antipsychotic medication, and mortality when creating a psychopharmacological treatment plan for their patients.
