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Trazodone may not stop, delay dementia onset

Researchers found no statistically significant association between trazodone use and a reduced risk for dementia among older adults compared with other antidepressants, according to a population- based cohort study published in PLOS Medicine.

“Recent 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,” Ruth Brauer, PhD, and Wallis Lau, PhD, of the University College London School of Pharmacy, told Healio Psychiatry. “Our study was the first to examine the effect of trazodone on dementia risk in humans.”

The investigators evaluated data from medical records of over 15 million primary care patients in the U.K. to determine whether there’s an association between trazodone use and dementia incidence. They compared adults aged 50 years and older with at least two consecutive trazodone prescriptions (received between 2000 and 2017) to adults with similar baseline characteristics who took other antidepressants. After propensity score matching, they analyzed 4,596 trazodone users and 22,980 users of other antidepressants.

Analysis revealed that the incidence of dementia was higher among trazodone users than that among matched antidepressant users (1.8 vs. 1.1 dementia cases per 100 person-years). The risk for dementia was also higher for trazodone users compared with other antidepressant users (HR = 1.8; 95% CI, 1.56-2.09). Furthermore, the median time to dementia diagnosis among those taking trazodone was 1.8 years compared with 4.1 years among those taking other antidepressants.

“While trazodone was suggested to be neuroprotective against dementia based on animal studies, our human study does not support such claim,” Brauer and Lau told Healio Psychiatry. “The findings of our study are fundamental to the planning of any future trials of drug repurposing for dementia.”

Additional analyses yielded similar results, according to the researchers.

When Brauer and colleagues changed the primary outcome variable from a generic dementia diagnosis to Alzheimer’s disease, they found no evidence of an association (HR = 0.8; 95% CI, 0.5-1.29). After censoring follow-up at the end of trazodone therapy, analysis revealed a stronger association between trazodone use and dementia risk compared with the results of the main analysis (HR = 2.57; 95% CI, 2.11-3.11). Furthermore, stratified analysis indicated that short-term trazodone exposure to (less than 2 years) was more strongly linked to higher dementia risk.

However, the researchers noted that their findings do not point toward a causal association.

“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,” they wrote in the full study. – by Savannah Demko

Disclosure: Brauer and Lau report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.