Association Between Venlafaxine Exposure And Treatment Outcomes In Older Adults With Depression: Association entre l'exposition à la venlafaxine et les résultats du traitement chez les personnes âgées atteintes de dépression.
Document Type
Article
Publication Date
9-2026
Identifier
DOI: 10.1177/07067437261451057; PMCID: PMC13176123
Abstract
Background Venlafaxine is commonly prescribed for older adults with depression, yet the relationship between venlafaxine-related exposure and treatment outcomes remains unclear. We aimed to assess the association of exposure to venlafaxine, its active metabolite O-desmethylvenlafaxine (ODV) and its active moiety (i.e., venlafaxine + ODV) with treatment response and adverse effects in late-life depression. Method We analyzed data from 325 participants from the Incomplete Response in Late-Life Depression: Getting to Remission (IRL-GRey) study. Participants were ≥ 60 years old, treated openly with venlafaxine (up to 300 mg/day) for 12 weeks. Treatment response was assessed with the Montgomery-Asberg Depression Rating Scale and adverse effects were evaluated with the Udvalg for Kliniske Undersøgelser (UKU) rating scale. Venlafaxine-related exposures were derived from a published population pharmacokinetic model based on the IRL-GRey study, and their associations with treatment outcomes were assessed using regression analyses. Result At week 4, the primary endpoint, higher venlafaxine-related exposures were not associated with greater symptom improvement. While at the end of treatment (week 12), we did not observe additional antidepressant benefit with increased venlafaxine-related exposures, higher ODV and active moiety exposures were associated with the occurrence of at least one adverse effect (odds ratio [OR] = 1.6 [1.1, 2.3], p = 0.02). Conclusion Our findings suggest a potential threshold effect, where venlafaxine-related exposure past a certain level did not enhance antidepressant response but increased adverse-effect burden. These results support incorporating exposure measures from therapeutic drug monitoring in antidepressant studies to address the heterogeneity of safety and tolerability outcomes.
Journal Title
Canadian journal of psychiatry. Revue canadienne de psychiatrie
Volume
71
Issue
9
First Page
691
Last Page
702
MeSH Keywords
Humans; Venlafaxine Hydrochloride; Female; Male; Aged; Middle Aged; Outcome Assessment, Health Care; Serotonin and Noradrenaline Reuptake Inhibitors; Major Depressive Disorder; Treatment Outcome; Antidepressive Agents, Second-Generation
PubMed ID
42131982
Keywords
Adverse effects; antidepressants; geriatric psychiatry; major depressive disorder; pharmacokinetics
Recommended Citation
Men X, Taylor ZL, Marshe VS, et al. Association Between Venlafaxine Exposure And Treatment Outcomes In Older Adults With Depression: Association entre l'exposition à la venlafaxine et les résultats du traitement chez les personnes âgées atteintes de dépression. Can J Psychiatry. 2026;71(9):691-702. doi:10.1177/07067437261451057
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