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Suicidal ideation and behavior in adults with major depressive disorder treated with vortioxetine: post hoc pooled analyses of randomized, placebo-controlled, short-term and open-label, long-term extension trials

  • Atul R. Mahableshwarkar (a1), John Affinito (a2), Elin Heldbo Reines (a3), Judith Xu (a4), George Nomikos (a5) and Paula L. Jacobsen (a6)...



This study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD).


Suicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6–8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data.


At baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-, 15-, and 20-mg groups, respectively), or duloxetine (11.3%). The incidence of suicide-related events for TEAEs in the short-term pool was 0.4% for placebo, 0.2% or 1.0% for vortioxetine 5 mg or 10 mg, and 0.7% each for vortioxetine 15 mg and 20 mg, as well as duloxetine. After 52-week treatment with vortioxetine, suicidal ideation based on C-SSRS was 9.8%, C-SSRS suicidal behavior was 0.2%, and the incidence of suicide-related events based on TEAEs was <1%. There were no completed suicides in any study.


Vortioxetine is not associated with increased risk of suicidal ideation or behavior in MDD patients.


Corresponding author

*Address correspondence to: Paula L. Jacobsen, Neuroscience, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL 60015, USA. (Email:


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Assistance with manuscript preparation was provided by Andrea McReynolds, PhD, and Martina Schwarzkopf, PhD, of inVentiv Medical Communications, LLC, a Syneos Health™ group company, and supported by Takeda Pharmaceutical Company, Ltd., and H. Lundbeck A/S. All authors assume full responsibility for the scientific content of the manuscript. The study was funded by Takeda Pharmaceutical Company, Ltd., and H. Lundbeck A/S.



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