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Obesity and depression are common comorbid conditions. The objective of the study was to evaluate the effect of obesity on the pharmacokinetics of the serotonergic antidepressant vortioxetine.Vortioxetine pharmacokinetics were evaluated in 16 otherwise healthy obese volunteers (mean weight, 119 kg; mean body mass index (BMI) 41.8 kg/m2) and in 14 normal-weight subjects (mean weight, 68 kg; mean BMI, 23.0 kg/m2) matched for age. All subjects received a single 5-mg oral dose of vortioxetine once daily for 29 days. Pre-dose plasma vortioxetine concentrations were measured during the 29 days of dosing, and during a 4-week washout period after the last dose. Full 24-hour profiles were obtained after the first and last doses.Vortioxetine accumulated extensively over the 29 days; the accumulation ratio was not significantly different between obese and control groups (means: 5.24 and 4.46, respectively). Steady-state concentration (Css) and steady-state clearance also did not differ between groups. However mean washout half-life (T1/2) was significantly prolonged in obese vs. control subjects (3.26 days vs. 2.21 days, P < 0.01). Up to 89% of the individual variability in T1/2 was explained by the product of Css and numeric indicators of the degree of obesity.The half-life of vortioxetine washout after discontinuation of therapy is significantly prolonged in obese individuals compared to normal weight controls. To avoid a potential risk of serotonin syndrome, obese patients who plan to change their medication from vortioxetine to a monoamine oxidase inhibitor (MAOI) should extend the time between vortioxetine discontinuation and MAOI initiation beyond what is recommended in the product label.