Vortioxetine Half-Life
The mean terminal half-life of vortioxetine is approximately 66 hours, with steady-state plasma concentrations typically achieved within two weeks of once-daily dosing. 1
Pharmacokinetic Profile
Vortioxetine exhibits a mean terminal half-life of approximately 66 hours across the therapeutic dose range of 2.5 to 60 mg, with linear and dose-proportional pharmacokinetics when administered once daily 1
The extended half-life means that steady-state plasma concentrations are generally achieved within 2 weeks of dosing, which is clinically relevant for both therapeutic onset and discontinuation planning 1, 2
Peak plasma concentrations (Cmax) are reached within 7 to 11 hours post-dose (Tmax), with absolute oral bioavailability of 75% 1
Clinical Implications of the Long Half-Life
Discontinuation Considerations
Vortioxetine's long half-life (66 hours) provides a significant advantage during discontinuation, as the extended washout period substantially reduces the risk of withdrawal or discontinuation syndromes 3
Unlike antidepressants with shorter half-lives that require careful tapering protocols, vortioxetine's prolonged elimination allows for more gradual natural washout even with abrupt cessation 3
Missed Doses
- Occasional missed doses are less clinically significant due to the 66-hour half-life, as plasma concentrations decline slowly and therapeutic levels are maintained for extended periods 3
Time to Steady State and Washout
The long half-life means vortioxetine takes approximately 2 weeks to reach steady state, which is rarely problematic for therapeutic initiation 3
Conversely, complete washout requires extended time, which becomes a disadvantage if rapid drug elimination is needed due to adverse effects, toxicity, or discovery of unplanned pregnancy 3
Metabolism and Population Variations
Vortioxetine is extensively metabolized primarily through CYP2D6, with additional metabolism via CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8, and CYP2B6 1
CYP2D6 poor metabolizers have approximately twice the vortioxetine plasma concentration of extensive metabolizers, which is the only intrinsic factor requiring dose adjustment 1
No clinically significant differences in vortioxetine exposure occur based on age, gender, ethnicity, renal function, or hepatic function, eliminating the need for dose adjustments in these populations 1, 4