Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers

Alice L. La, Christine M. Walsh, Thomas C. Neylan, Keith A. Vossel, Kristine Yaffe, Andrew D. Krystal, Bruce L. Miller, Elissaios Karageorgiou

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Recent studies reveal an association between slow-wave sleep (SWS), amyloid-β aggregation, and cognition. Objective: This retrospective study examines whether long-term use of trazodone, an SWS enhancer, is associated with delayed cognitive decline. Methods: We identified 25 regular trazodone users (mean age 75.4±7.5; 9 women, 16 men) who carried a diagnosis of Alzheimer's dementia, mild cognitive impairment, or normal cognition, and 25 propensity-matched trazodone non-users (mean age 74.5±8.0; 13 women, 12 men), accounting for age, sex, education, type of sleep deficit (hypersomnia, insomnia, parasomnia), diagnosis, and baseline Mini-Mental State Examination (MMSE). Longitudinal group differences in cognitive testing were evaluated through repeated measures tests over an average inter-evaluation interval of four years. Results: Trazodone non-users had 2.6-fold faster decline MMSE (primary outcome) compared to trazodone users, 0.27 (95% confidence interval [CI]: 0.07-0.48) versus 0.70 (95% CI: 0.50-0.90) points per year (p = 0.023). The observed effects were especially associated with subjective improvement of sleep complaints in post-hoc analyses (p = 0.0006). Secondary outcomes of other cognitive and functional scores had variable worsening in non-users and varied in significance when accounting for co-administered medications and multiple comparisons. Trazodone effects on MMSE remained significant within participants with AD-predicted pathology, with 2.4-fold faster decline in non-users (p = 0.038). Conclusions: These results suggest an association between trazodone use and delayed cognitive decline, adding support for a potentially attractive and cost-effective intervention in dementia. Whether the observed relationship of trazodone to cognitive function is causal or an indirect marker of other effects, such as treated sleep disruption, and if such effects are mediated through SWS enhancement requires confirmation through prospective studies.

Original languageEnglish (US)
Pages (from-to)911-921
Number of pages11
JournalJournal of Alzheimer's Disease
Volume67
Issue number3
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Alzheimer's disease
  • dementia
  • hypnotics
  • mild cognitive impairment
  • sleep
  • treatment

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

La, A. L., Walsh, C. M., Neylan, T. C., Vossel, K. A., Yaffe, K., Krystal, A. D., Miller, B. L., & Karageorgiou, E. (2019). Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers. Journal of Alzheimer's Disease, 67(3), 911-921. https://doi.org/10.3233/JAD-181145