None of the interventions changed agitation compared to placebo. Participants had to be living at home, or not in an institution. It compared 16 weeks of trazodone (average mean dose 200 mg daily) to haloperidol, behavior management techniques, or placebo in 149 AD patients with moderate to severe cognitive impairment and agitation. Findingsįollowing anecdotal reports of trazodone’s effectiveness for agitation in people with AD, a Phase 3 trial was run in the late 1990s at 21 sites in the U.S. see Ringman and Schneider 2019).Ī placebo-controlled study at Colorado State University Veterinary Teaching Hospital is evaluating trazodone for age-related cognitive dysfunction in dogs ( TRAC study). This drug can increase the risk of falling, but is nonetheless used for older people with depression, and for severe agitation or insomnia in AD patients (e.g. Common side effects include dry mouth, feeling faint, hypotension, vomiting, and headache. In rTg4510 tau mice, it reduced neuroinflammation and tau pathology, and improved sleep and olfactory memory ( de Oliveira et al., 2022).įor treatment of depression, doses range from 150-300 mg per day, and can go up to 600 mg. There is also emerging evidence from preclinical studies for a possible disease-modifying effect due to trazodone’s ability to enhance proteostasis and protect against neurodegeneration in models of prion disease and frontotemporal dementia ( Halliday et al., 2017 also see review by Sidhom et al., 2022). Slowing of cognitive decline was associated with subjective reports of sleep improvement. In an observational study of people with AD, MCI, or normal cognition but attending a sleep clinic, those using trazadone showed significantly slower decline in MMSE scores over four years than a matched group who did not take the drug ( La et al., 2019 commentary by Ashford, 2019 also Burke et al., 2018). Disruption of slow-wave sleep by amyloid and tau deposition appears to contribute to cognitive problems (e.g., Mander et al., 2015 Lucey et al., 2019). Compared to other sleep medications, trazodone has a unique effect of prolonging and deepening slow-wave sleep. Recent interest in trazodone is focused on its potential to slow cognitive loss by improving sleep in people with early stage memory loss or dementia. Taken as a tablet, trazodone is available as a generic. It is widely used off-label for insomnia and anxiety disorders, and to treat agitation and sleep disturbances in people with Alzheimer’s disease. It was approved more than 40 years ago to treat major depressive disorder. Trazodone is a phenyl piperazine derivative with agonist and antagonist activity at serotonin receptors, in addition to adrenergic and histaminergic activity and serotonin uptake inhibition. FDA Status: Alzheimer's Disease (Phase 3), Mild Cognitive Impairment (Phase 3), Amyotrophic Lateral Sclerosis (Phase 2/3) Approved for: Depression Background Name: Trazodone Synonyms: Trazodone hydrochloride, Oleptro, Desyrel Chemical Name: 2-triazolopyridin-3(2H)-one Therapy Type: Small Molecule (timeline) Target Type: Other Neurotransmitters (timeline) Condition(s): Alzheimer's Disease, Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis U.S. How would you like to share? Facebook Twitter LinkedIn
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