Summary: Researchers report they have found no statistically significant evidence to back up previous claims the antidepressant Trazodone reduces dementia risks, when compared to other antidepressants.
In a large UK population-based study, Ian Wong and colleagues at the University of Hong Kong and University College London, UK, found no statistically significant association between the antidepressant trazodone and a reduced risk of dementia when compared to other antidepressants. Their findings were published this week in PLOS Medicine.
In vitro and animal studies have previously suggested that trazodone may protect against dementia. In the new study, researchers analyzed data from the Health Improvement Network (THIN), which includes medical records of over 15 million primary care patients in the UK. They identified 4,716 people over the age of 50 years who received at least two consecutive trazodone prescriptions between 2000 and 2017, and compared them with 420,280 users of other antidepressants with similar baseline characteristics.
The median time to dementia diagnosis for trazodone users was 1.8 years. The incidence of dementia among trazodone users was higher than in matched antidepressant users (1.8 vs 1.1 dementia cases per 100 person-years) with a hazard ratio of 1.80 (95% confidence interval 1.56-2.09, P < 0.001). However, the results do not point toward a causal association; the study is limited by the fact that people in the prodromal stage of dementia might be preferentially prescribed trazodone.
“These results refute the suggestions from animal studies that trazodone might stop or delay the onset of dementia in patients at the prodromal stage of dementia,” the authors say.
Funding: RB is funded by a UCL Maplethorpe Fellowship and the collaboration between the Department of Pharmacology and Pharmacy of the University of Hong Kong, and the UCL School of Pharmacy is funded by The University of Hong Kong-University College London (HKU-UCL) Strategic Partnership Fund. JFH is funded by a Wellcome Trust Clinical Research Career Development Fellowship. JFH, DPJO, and RH are supported by the UCLH NIHR Biomedical Research Center.
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Original Research: Open access research for “Trazodone use and risk of dementia: A population-based cohort study” by Ruth Brauer, Wallis C. Y. Lau, Joseph F. Hayes, Kenneth K. C. Man, David P. J. Osborn, Robert Howard, Joseph Kim, and Ian C. K. Wong in PLOS Medicine. Published February 5 2019.
Trazodone use and risk of dementia: A population-based cohort study
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.
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.