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. 2019 Feb 5;16(2):e1002728.
doi: 10.1371/journal.pmed.1002728. eCollection 2019 Feb.

Trazodone use and risk of dementia: A population-based cohort study

Ruth Brauer  1 , Wallis C Y Lau  1   2 , Joseph F Hayes  3 , Kenneth K C Man  1   2   4   5 , David P J Osborn  3 , Robert Howard  3 , Joseph Kim  1   6   7 , Ian C K Wong  1   2   8
Affiliations

Trazodone use and risk of dementia: A population-based cohort study

Ruth Brauer et al. PLoS Med. .

Abstract

Background: In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice.

Methods and findings: The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding.

Conclusions: In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: ICKW has received research funding from Bristol-Myers Squibb, Pfizer, Janssen, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund outside the submitted work. KKCM has received personal fees from IQVIA outside the submitted work. JK is an employee of IQVIA. There are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1. Flow of patients.
See this image and copyright information in PMC

References

    1. Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–734. 10.1016/S0140-6736(17)31363-6 - DOI - PubMed
    1. Xu JF, Zhang YQ, Qiu CX, Cheng F. Global and regional economic costs of dementia: a systematic review. Lancet. 2017;390:S47–S. 10.1016/S0140-6736(17)33185-9 - DOI
    1. Pinquart M, Sorensen S. Differences between caregivers and noncaregivers in psychological health and physical health: A meta-analysis. Psychol Aging. 2003;18(2):250–67. 10.1037/0882-7974.18.2.250 - DOI - PubMed
    1. Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry. 1999;174:45–50. - PubMed
    1. Irvine GB, El-Agnaf OM, Shankar GM, Walsh DM. Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases. Molecular medicine. 2008;14(7–8):451–64. 10.2119/2007-00100.Irvine - DOI - PMC - PubMed

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