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Trazodone does not reduce risk of dementia

Stephen Padilla
12 Feb 2019

There is no association between trazodone use and a lower risk of dementia compared with other antidepressants, according to a study of population-based electronic health records in the UK, refuting suggestions from animal studies that trazodone might stop or delay the onset of dementia in patients at the prodromal stage.

“[W]e found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. The results were consistent across different patient subgroups, definitions of dementia outcomes and treatment durations, as well as when comparing specific antidepressants to trazodone,” researchers said.

A total of 4,716 patients (59.2 percent female) prescribed trazodone were included in the study. Participants were older (mean age 70.9 vs 65.6 years) and were more likely to have cerebrovascular disease and to use anxiolytic or antipsychotic drugs than those prescribed other antidepressants.

Analysis was conducted in 4,596 users of trazodone and 22,980 users of other antidepressants after propensity score matching. People prescribed trazodone had a median time to dementia diagnosis of 1.8 years (interquartile range, 0.5–5.0 years). [PLoS Med 2019;16:e1002728]

Incidence of dementia was higher among patients taking trazodone than in those using other antidepressants (1.8 vs 1.1 per 100 person-years; hazard ratio [HR], 1.80; 95 percent CI, 1.56–2.09; p<0.001). Results, however, did not suggest a causal relationship.

“We found that the incidence of dementia among patients taking trazodone was higher than that in patients taking other antidepressants,” researchers said. “However, our results do not suggest that this association was causal—the risk differences were closer to zero with increasing duration of treatment, suggesting the possibility of reverse causality, in which people in the prodromal stage of dementia might be more likely to be prescribed trazodone.”

Specifically, individuals with sleep problems may be prescribed trazodone. Of note, sleep problems may be an early sign of dementia and independently predict Alzheimer dementia (AD). [Br Med J 2015;350:h369; Nature Rev Neurol 2014;10:115-119]

In a sensitivity analysis that restricted the control group to users of mirtazapine only, findings were comparable to those of the main analysis.

“Our study findings are consistent with those of the only [randomized controlled trial] that has examined cognitive outcomes in patients with mild to moderate AD taking trazodone, which reported that trazodone had no positive effect on cognition when compared to placebo,” researchers said. [Am J Geriatr Psychiatry 2014;22:1565-1574]

“Another RCT of trazodone as a sleep aid in patients with insomnia reported small impairments in short-term memory in trazodone users,” they added. [J Sleep Res 2011;20:552-558]

The present study used The Health Improvement Network (THIN), an archive of anonymized medical and prescribing records from primary care practices in the UK, which contains records of over 15 million patients. Researchers identified patients aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017.

Cox regression model with 1:5 propensity score matching was used to compare the risk of dementia among patients prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants.

This study was limited by the possibility of indication bias due to patients in the prodromal stage of dementia who might be preferentially prescribed trazodone. Residual confounding cannot be ruled out as well because of the observational nature of this study.

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