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Eur J Clin Pharmacol ; 77(11): 1623-1637, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34097124

ABSTRACT

Trazodone is a widely used antidepressant that is also useful in the control of agitation and insomnia in Alzheimer's disease. This drug is now recognized as having a new mechanism of action, an effect on the unfolded protein response (UPR) pathway, restoring protein translation and slowing neurodegenerative progression in mice. This mechanism may have a role in dementia-modifying treatment. To explore the effects of trazodone on human cognition and to search for clinical evidence of its putative benefits in human neurodegenerative diseases, a systematic review was conducted for studies that evaluated the effect of a minimum dose of 25 mg of trazodone daily, for at least 1 week, on cognition in adult humans. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases, yielding a total of 16 studies after selection. Overall, seven studies showed no effect of trazodone on cognition, five showed a beneficial effect by improving or reducing cognitive decline, and four evidenced impaired cognitive function. Our analysis highlights the possibility of a dose-independent dual effect of trazodone on human cognition, with acute utilization associated with impaired cognitive function and long-term use with preventing cognitive deterioration. There was no clinical evidence that trazodone could be used as a specific treatment of neurodegenerative diseases. Future studies should explore the role of trazodone in the UPR pathway and the implications in neurodegenerative diseases in humans.


Subject(s)
Antidepressive Agents, Second-Generation/therapeutic use , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/prevention & control , Trazodone/therapeutic use , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/pharmacology , Cognition/drug effects , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/prevention & control , Cross-Over Studies , Dose-Response Relationship, Drug , Neurodegenerative Diseases/chemically induced , Randomized Controlled Trials as Topic , Time Factors , Trazodone/adverse effects , Trazodone/pharmacology
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