ArticleJournal of Alzheimer's disease : JAD2019
Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Pooled it
- Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis.Scientific reports · 2022Pooled it
- The effects of trazodone on human cognition: a systematic review.European journal of clinical pharmacology · 2021Pooled it
- Gamma-hydroxybutyrate to promote slow-wave sleep in major depressive disorder: a randomized crossover trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).Journal of Alzheimer's disease : JAD · 2024Trial
- Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Crossroads of Neurodegeneration: Exploring the Overlap Between Alzheimer's Disease and Depression.Cureus · 2026Review
- Subjective sleep characteristics in non-demented adults: domain-specific associations with multimodal Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A Deep Subgrouping Framework for Precision Drug Repurposing via Emulating Clinical Trials on Real-world Patient Data.KDD : proceedings. International Conference on Knowledge Discovery & Data Mining · 2025Article
- The effects of acute trazodone administration on sleep in mice.Sleep advances : a journal of the Sleep Research Society · 2025Article
- The locus coeruleus, a blue spot for early diagnosis and prognosis of Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Ultra-Long-Term-EEG Monitoring (ULTEEM) Systems: Towards User-Friendly Out-of-Hospital Recordings of Electrical Brain Signals in Epilepsy.Sensors (Basel, Switzerland) · 2024Article
- Chronic Aripiprazole and Trazodone Polypharmacy Effects on Systemic and Brain Cholesterol Biosynthesis.Biomolecules · 2023Article
- Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Associations Between Objectively Measured Sleep and Cognition: Main Effects and Interactions With Race in Adults Aged ≥50 Years.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Race Differences in the Association Between Sleep Medication Use and Risk of Dementia.Journal of Alzheimer's disease : JAD · 2023Article
- Impact of transcutaneous vagus nerve stimulation on healthy cognitive and brain aging.Frontiers in neuroscience · 2023Review
- Treating depression in clinical practice: new insights on the multidisciplinary use of trazodone.Frontiers in psychiatry · 2023Review
- Chronic Trazodone and Citalopram Treatments Increase Trophic Factor and Circadian Rhythm Gene Expression in Rat Brain Regions Relevant for Antidepressant Efficacy.International journal of molecular sciences · 2022Article
- Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundRecent studies reveal an association between slow-wave sleep (SWS), amyloid-β aggregation, and cognition.
objectiveThis retrospective study examines whether long-term use of trazodone, an SWS enhancer, is associated with delayed cognitive decline.
methodsWe 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.
resultsTrazodone 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).
conclusionsThese 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.