Use of sedative‐hypnotic medications and risk of dementia: A systematic review and meta‐analysis

Asma AlDawsari; Trevor J. Bushell; Nouf Abutheraa; Shuzo Sakata; Sarah Al Hussain; Amanj Kurdi

doi:10.1111/bcp.15113

Use of sedative‐hypnotic medications and risk of dementia: A systematic review and meta‐analysis

Asma AlDawsari^* (Corresponding Author), Trevor J. Bushell, Nouf Abutheraa, Shuzo Sakata, Sarah Al Hussain, Amanj Kurdi

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

1 Downloads (Pure)

Abstract

Aims: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. Methods: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. Results: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19–1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23–1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48–1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97–1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13–2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17–1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88–1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68–1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85–1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0–1.44) and (OR: 1.22, 95% CI 0.75–2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82–1.58), Z-drugs (OR: 1.29, 95% CI 0.78–2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91–2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23–3.39). Conclusions: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.

Original language	English
Pages (from-to)	1567-1589
Number of pages	23
Journal	British Journal of Clinical Pharmacology
Volume	88
Issue number	4
Early online date	22 Oct 2021
DOIs	https://doi.org/10.1111/bcp.15113
Publication status	Published - 1 Apr 2022

Bibliographical note

Acknowledgements
This research received no specific grant from any funding agency, commercial or not-for profit sectors.

Data Availability Statement

Supporting Information
Additional supporting information may be found in the online version of the article at the publisher's website

Data Availability
The data that support the findings of this study are available on request from the corresponding author.

Keywords

antidepressants
antipsychotics
benzodiazepines
dementia
sedative-hypnotics

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AlDawarsi_etal_BJP_Use_Of_Sedative_AAM
This is the peer reviewed version of the following article: AlDawsari A, Bushell TJ, Abutheraa N,Sakata S, Al Hussain S, Kurdi A. Use of sedative-hypnoticmedications and risk of dementia: A systematic review andmeta-analysis.Br J Clin Pharmacol. 2022;88(4):1567-1589 which has been published in final form at https://doi.org/10.1111/bcp.15113. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Accepted author manuscript, 7.11 MBLicence: Other

Cite this

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title = "Use of sedative‐hypnotic medications and risk of dementia: A systematic review and meta‐analysis",

abstract = "Aims: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. Methods: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. Results: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19–1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23–1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48–1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97–1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13–2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17–1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88–1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68–1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85–1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0–1.44) and (OR: 1.22, 95% CI 0.75–2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82–1.58), Z-drugs (OR: 1.29, 95% CI 0.78–2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91–2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23–3.39). Conclusions: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.",

keywords = "antidepressants, antipsychotics, benzodiazepines, dementia, sedative-hypnotics",

author = "Asma AlDawsari and Bushell, {Trevor J.} and Nouf Abutheraa and Shuzo Sakata and Hussain, {Sarah Al} and Amanj Kurdi",

note = "Acknowledgements This research received no specific grant from any funding agency, commercial or not-for profit sectors.",

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doi = "10.1111/bcp.15113",

language = "English",

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TY - JOUR

T1 - Use of sedative‐hypnotic medications and risk of dementia

T2 - A systematic review and meta‐analysis

AU - AlDawsari, Asma

AU - Bushell, Trevor J.

AU - Abutheraa, Nouf

AU - Sakata, Shuzo

AU - Hussain, Sarah Al

AU - Kurdi, Amanj

N1 - Acknowledgements This research received no specific grant from any funding agency, commercial or not-for profit sectors.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Aims: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. Methods: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. Results: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19–1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23–1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48–1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97–1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13–2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17–1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88–1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68–1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85–1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0–1.44) and (OR: 1.22, 95% CI 0.75–2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82–1.58), Z-drugs (OR: 1.29, 95% CI 0.78–2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91–2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23–3.39). Conclusions: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.

AB - Aims: Growing evidence suggests an association between the use of sedative-hypnotic medications and risk of dementia. The aim of this study is to examine this association using a meta-analysis approach. Methods: MEDLINE (PubMed) and Scopus were systematically searched for studies published in English only. The quality of studies was evaluated using the Newcastle-Ottawa scale, and an overall odds ratio was pooled using a random-effects model. Results: A total of 35 articles were included in the analysis. Pooled odds ratios (ORs) for dementia from all records were (OR; 1.33, 95% CI 1.19–1.49) for benzodiazepine (BZD) combined use (Subgroup-1), (OR: 1.46, 95% CI 1.23–1.73) for short-acting BZD use (Subgroup-2), (OR: 1.72, 95% CI 1.48–1.99) for long-acting BZD use (Subgroup-3), (OR: 1.13, 95% CI 0.97–1.32) for BZDs without specification of duration of action (Subgroup-4), (OR: 1.64, 95% CI 1.13–2.38) for the combined BZDs and Z-drugs, (OR: 1.43, 95% CI 1.17–1.74) for Z-drugs only, (OR: 1.14, 95% CI 0.88–1.46) for antidepressant use, (OR: 0.97, 95% CI 0.68–1.39) for antipsychotic use and (OR: 0.98, 95% CI 0.85–1.13) for anticonvulsant use. When sensitivity analysis was performed, association between overall use of BZDs and short-acting BZDs with the increased risk of dementia disappeared after exclusion of studies that were not adjusted for age covariate (OR: 1.2, 95% CI 1.0–1.44) and (OR: 1.22, 95% CI 0.75–2.01), respectively. Adjustment for protopathic bias by introduction of a lag period showed no evidence of increased risk of dementia with the use of BZDs (Subgroup-1) (OR: 1.14, 95% CI 0.82–1.58), Z-drugs (OR: 1.29, 95% CI 0.78–2.13), and combined BZDs and Z-drugs (OR: 1.51, 95% CI 0.91–2.53). Combined use of BZDs and Z-drugs showed more positive association when only studies of non-user design were analysed (OR: 2.75, 95% CI 2.23–3.39). Conclusions: All the investigated sedative-hypnotics showed no association with increased risk of dementia except for BZDs. However, the observed association with BZDs did not persist after exclusion of studies with potential reverse causation and confounding by indication. Therefore, this association needs to be assessed carefully in future research.

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Use of sedative‐hypnotic medications and risk of dementia: A systematic review and meta‐analysis

Abstract

Bibliographical note

Data Availability Statement

Keywords

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