Abstract
Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008-16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03-0·49; p=0·03). Results in sensitivity analyses were consistent with primary analyses. There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.
Highlights
There are no successful disease modifying treatments for dementia,[1] intensifying the need for the identification of new treatment approaches
In this naturalistic cohort study in people with clinically diagnosed dementia who were prescribed one of three antidepressants, we found no evidence of cognitive benefit of trazodone in either all‐ cause dementia or non‐vascular dementias
We found an absence of cognitive benefit from trazodone in all three clinical sites, as well as when combined in meta‐analysis
Summary
There are no successful disease modifying treatments for dementia,[1] intensifying the need for the identification of new treatment approaches. As trazodone is prescribed for non‐cognitive symptoms of dementia which may reflect more rapidly progressive dementia,[11] we compared trazodone with citalopram and mirtazapine; antidepressant drugs which do not have effect on eIF2α‐P2 but are prescribed for similar indications. Our specific objectives were to: compare the cognitive trajectory of people with dementia who were prescribed trazodone with those prescribed citalopram or mirtazapine examine these associations in people with non‐vascular dementia subtypes because the PERK/eIF2α‐P pathway is not pathogenic in vascular dementias
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