Skip to main content Accessibility help
×
Home

Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis

  • Paula L. Jacobsen (a1), Atul R. Mahableshwarkar (a1), William A. Palo (a1), Yinzhong Chen (a1), Marianne Dragheim (a2) and Anita H. Clayton (a3)...

Abstract

Objective

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.

Methods

Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5–20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.

Results

TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.

Conclusions

Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis
      Available formats
      ×

Copyright

The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

*Address for correspondence: Paula L. Jacobsen, Takeda Development Center Americas, Inc., One Takeda Parkway, Deerfield, IL 60015, USA. (Email: paula.jacobsen@takeda.com)

Footnotes

Hide All

This study was supported by the Takeda Pharmaceutical Company, Ltd., and H. Lundbeck A/S. Assistance with writing and manuscript preparation was provided by Ken Scholz, PhD, and Philip Sjostedt, BPharm, with The Medicine Group, and was paid for by the Takeda Pharmaceutical Company, Ltd. and H. Lundbeck A/S. The authors are entirely responsible for the scientific content of the paper.

Footnotes

References

Hide All
1. Angst, J. Sexual problems in healthy and depressed persons. Int Clin Psychopharmacol. 1998; 13(Suppl 6): S1S4.
2. Kennedy, SH, Rizvi, S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol. 2009; 29(2): 157164.
3. Montejo, AL, Llorca, G, Izquierdo, JA, Rico-Villademoros, F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001; 62(Suppl 3): 1021.
4. Clayton, AH, Pradko, JF, Croft, HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002; 63(4): 357366.
5. Serretti, A, Chiesa, A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009; 29(3): 259266.
6. Williams, VS, Edin, HM, Hogue, SL, Fehnel, SE, Baldwin, DS. Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey. J Psychopharmacol. 2010; 24(4): 489496.
7. Baldwin, DS, Palazzo, MC, Masdrakis, VG. Reduced treatment-emergent sexual dysfunction as a potential target in the development of new antidepressants. Depress Res Treat. 2013; 2013: 256841.
8. Reichenpfader, U, Gartlehner, G, Morgan, LC, et al. Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf. 2014; 37(1): 1931.
9. Hu, XH, Bull, SA, Hunkeler, EM, et al. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry. 2004; 65(7): 959965.
10. Graf, H, Walter, M, Metzger, CD, Abler, B. Antidepressant-related sexual dysfunction—perspectives from neuroimaging. Pharmacol Biochem Behav. 2014; 121: 138145.
11. Olivier, B, Chan, JS, Snoeren, EM, et al. Differences in sexual behaviour in male and female rodents: role of serotonin. Curr Top Behav Neurosci. 2011; 8: 1536.
12. Fabre, LF, Clayton, AH, Smith, LC, Goldstein, I, Derogatis, LR. The effect of gepirone-ER in the treatment of sexual dysfunction in depressed men. J Sex Med. 2012; 9(3): 821829.
13. Keltner, NL, McAfee, KM, Taylor, CL. Mechanisms and treatments of SSRI-induced sexual dysfunction. Perspect Psychiatr Care. 2002; 38(3): 111116.
14. Bang-Andersen, B, Ruhland, T, Jorgensen, M, et al. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011; 54(9): 32063221.
15. Oosting, RS, Chan, JSW, Pehrson, A, Li, Y, Sanchez, C, Olivier, B. P-42-016 Vortioxetine does not affect sexual behavior in a male rat model for sexual dysfunction [abstract]. Int J Neuropsychopharmacol. 2014; 17(S1): 138.
16. Katona, C, Katona, C. New generation multi-modal antidepressants: focus on vortioxetine for major depressive disorder. Neuropsychiatr Dis Treat. 2014; 10: 349354.
17. Baldwin, DS, Loft, H, Dragheim, M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol. 2012; 22(7): 482491.
18. Boulenger, J-P, Loft, H, Olsen, CK. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol. 2014; 29(3): 138149.
19. Mahableshwarkar, A, Jacobsen, P, Chen, Y, Serenko, M, Trivedi, M. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015; 232(12): 20612070.
20. Mahableshwarkar, A, Jacobsen, P, Serenko, M, Chen, Y, Trivedi, M. A randomized, double-blind, placebo-controlled study of the efficacy and safety of 2 doses of vortioxetine in adults with major depressive disorder. J Clin Psychiatry. 2015; 76(5): 583591.
21. Jacobsen, P, Mahableshwarkar, A, Serenko, M, Chan, S, Trivedi, M. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with major depressive disorder. J Clin Psychiatry. 2015; 76(5): 575582.
22. Mahableshwarkar, AR, Jacobsen, PL, Chen, Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013; 29(3): 217226.
23. Mahableshwarkar, AR, Jacobsen, PL, Chen, Y, Simon, JS. A randomised, double-blind, placebo-controlled, duloxetine-referenced study of the efficacy and tolerability of vortioxetine in the acute treatment of adults with generalised anxiety disorder. Int J Clin Pract. 2014; 68(1): 4959.
24. McGahuey, CA, Gelenberg, AJ, Laukes, CA, et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Ther. 2000; 26(1): 2540.
25. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.. Washington, DC: American Psychiatric Association; 2000.
26. Sánchez-Meca, J, Marín-Martínez, F. Meta-analysis of 2×2 tables: estimating a common risk difference. Educational and Psychological Measurement. 2001; 61(2): 249276.
27. Reviewer Guidance—Conducting a Clinical Safety Review of a New Product Application and Preparing a Report on the Review. 2005. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072974.pdf. Accessed July 2, 2014.
28. Landen, M, Hogberg, P, Thase, ME. Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine. J Clin Psychiatry. 2005; 66(1): 100106.
29. Detke, MJ, Wiltse, CG, Mallinckrodt, CH, McNamara, RK, Demitrack, MA, Bitter, I. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol. 2004; 14(6): 457470.
30. Clayton, A, Kornstein, S, Prakash, A, Mallinckrodt, C, Wohlreich, M. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sex Med. 2007; 4(4 Pt 1): 917929.

Keywords

Related content

Powered by UNSILO
Type Description Title
WORD
Supplementary materials

Jacobsen supplementary material
Appendix 1-2

 Word (30 KB)
30 KB

Treatment-emergent sexual dysfunction in randomized trials of vortioxetine for major depressive disorder or generalized anxiety disorder: a pooled analysis

  • Paula L. Jacobsen (a1), Atul R. Mahableshwarkar (a1), William A. Palo (a1), Yinzhong Chen (a1), Marianne Dragheim (a2) and Anita H. Clayton (a3)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.