NCMD Seminar Series Presents 'How CYP2D6 Affects Venlafaxine Pharmacokinetics and Its Impact on Clinical Outcomes in Older Adults with Depression'

This week for our NCMD seminar, we were very grateful to host Xiaoyu (Betsy) Men from the University of Toronto who delivered a brilliant presentation on 'How CYP2D6 Affects Venlafaxine Pharmacokinetics and Its Impact on Clinical Outcomes in Older Adults with Depression'.

Xiaoyu (Betsy) Men is a PhD candidate in Pharmacology at the University of Toronto. She joined the Pharmacogenetics Research Clinic at the Centre for Addiction and Mental Health in September 2020 under the supervision of Dr. Daniel Mueller. Her research focuses on investigating the genetic variability affecting antidepressant treatment responses in depression, using pharmacogenetic and pharmacokinetic strategies.

In this study, they used a population pharmacokinetic (PK) model to investigate whether CYP2D6 metabolizer status affected model-estimated PK parameters of VEN and its active metabolite O-desmethylvenlafaxine (ODV), as well as the relationship between VEN-related exposures and clinical outcomes in older adults with depression. Incorporating CYP2D6 metabolizer status significantly improved the model’s predictive accuracy. CYP2D6 metabolizers showed different VEN clearance, VEN exposure, and active moiety (VEN plus ODV) exposure, where differences were
mostly driven by CYP2D6 poor metabolizers. Regarding clinical outcomes, higher exposures to VEN, ODV, and its active moiety were associated with an increased risk of adverse effects, particularly nausea/vomiting and orthostatic dizziness, but not therapeutic efficacy. The study highlights the importance of CYP2D6 metabolizer status in optimizing VEN dosing strategies and underscores the clinical relevance of PK monitoring to minimize antidepressant adverse effects in older adults with depression.

Thank you so much Xiaoyu for this presentation!