Systematic Reviews/Meta-Analysis
Sunday, November 12, 2023
12:45 PM–02:15 PM
Abstract
Background: Vortioxetine has a multimodal action to treat major depression. In terms of its pharmacokinetics, little is known about subject-related intrinsic factors (e.g., sex). This study aims to determine whether sex affects vortioxetine pharmacokinetics in healthy men and women.
Methods: RCTs with sex-specific subgroup analyses were eligible. Risk of bias was assessed using the RoB 2 Cochrane Tool. To identify relevant articles and studies, PubMed, Embase, Cochrane, and Clinicaltrials.gov were searched. Vortioxetine pharmacokinetics and adverse events were the primary endpoints.
Results: Inclusion criteria were met by three studies. Following a single dose, women were exposed to vortioxetine more than men. Steady-state data showed similar trends. Men and women received different dose ranges. However, the pharmacokinetics were linear across all dose ranges. The difference between men and women in exposure (Cmax and AUC) was statistically significant, despite no clinically relevant differences. Vortioxetine exposure is significantly related to body weight and other size-related measurements, such as body mass index and lean body mass. Most commonly reported adverse events were nausea and headache; women reported nausea more than men.
Discussion: FDA drug labels did not differentiate between sexes for indications despite differences in pharmacokinetics. This variability has a sex-specific explanation, but there are significant gaps in our knowledge. This review has the advantage of using global vortioxetine data. The variability observed in the studies could not be comprehensively evaluated due to limited background information.
Other: Pharmacokinetic model-based studies are needed for both sex-specific and non-sex-specific changes in adult populations.
Presenting Author
Azizah Alawadhi Pharm D, MSc, BS PharmMCPHS
Authors