THE IMPACT OF VORTIOXETINE ON SEXUAL FUNCTION: A SYSTEMATIC REVIEW OF AVAILABLE CLINICAL DATA AND PHARMACOLOGICAL MECHANISMS
Abstract
Background: Sexual dysfunction is a common and often treatment-limiting side effect of antidepressants, especially SSRIs and SNRIs, impacting quality of life, adherence, and clinical outcomes in patients with major depressive disorder (MDD).
Objective: This systematic review assesses clinical and neurobiological evidence on the effects of vortioxetine—a multimodal antidepressant—on sexual function, comparing it to other antidepressants and exploring its potential to alleviate SSRI-induced sexual dysfunction.
Methods: A systematic literature search was conducted (PubMed, Embase, Web of Science, Cochrane Library) through June 2025, following PRISMA guidelines. Included studies reported on sexual outcomes in adults treated with vortioxetine, using validated tools such as ASEX or CSFQ.
Results: Vortioxetine was consistently associated with lower rates of treatment-emergent sexual dysfunction (TESD) than conventional SSRIs and SNRIs. Rates ranged from 1.1% to 16.2%, often similar to placebo and markedly lower than with paroxetine or venlafaxine. Case studies and observational data suggested vortioxetine may also improve pre-existing sexual dysfunction, including post-SSRI sexual dysfunction (PSSD), particularly in libido and orgasmic function. The most favorable outcomes were seen at doses between 5–15 mg/day.
Conclusions: Vortioxetine shows a favorable sexual tolerability profile and may reverse SSRI-induced sexual dysfunction. Its multimodal serotonergic activity likely underpins these benefits. While evidence supports its use in patients at risk for or experiencing TESD, more head-to-head trials with standardized outcome measures are needed.
References
Baldwin DS, Chrones L, Florea I, Nielsen R, Nomikos GG, Palo W, Reines E. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol. 2016) (3):242-52. doi: 10.1177/0269881116628440. Epub 2016 Feb 9. PMID: 26864543; PMCID: PMC4794082.
Jacobsen, Paula L., Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, i Madhukar H. Trivedi. „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”. The Journal of Clinical Psychiatry 76, nr 5 (2015): 575–82. https://doi.org/10.4088/JCP.14m09335.
Jacobsen, Paula L., Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, i Madhukar H. Trivedi. „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”. The Journal of Clinical Psychiatry 76, nr 5 (2015): 575–82. https://doi.org/10.4088/JCP.14m09335.
McDaniel, Brandon T., Victor Cornet, Jeanne Carroll, Lambros Chrones, Joseph Chudzik, Jeanette Cochran, Shion Guha, i in. „Real-World Clinical Outcomes and Treatment Patterns in Patients with MDD Treated with Vortioxetine: A Retrospective Study”. BMC Psychiatry 23, nr 1 (2023): 938. https://doi.org/10.1186/s12888-023-05439-8.
Baldwin DS, Chrones L, Florea I, Nielsen R, Nomikos GG, Palo W, Reines E. The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. J Psychopharmacol. 2016) (3):242-52. doi: 10.1177/0269881116628440. Epub 2016 Feb 9. PMID: 26864543; PMCID: PMC4794082.
Jacobsen, Paula L., Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, i Madhukar H. Trivedi. „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”. The Journal of Clinical Psychiatry 76, nr 5 (2015): 575–82. https://doi.org/10.4088/JCP.14m09335.
Baldwin, David S., Thomas Hansen, i Ioana Florea. „Vortioxetine (Lu AA21004) in the Long-Term Open-Label Treatment of Major Depressive Disorder”. Current Medical Research and Opinion 28, nr 10 (2012): 1717–24. https://doi.org/10.1185/03007995.2012.725035.
Dönmezler, Süleyman, Meltem Sen, i Münevver Hacioglu Yildirim. „A Case with Sexual Dysfunction Improved by Vortioxetine Dose Reduction and Sensate Focus Exercises”. The Journal of Neurobehavioral Sciences 8, nr 1 (2021): 78. https://doi.org/10.4103/jnbs.jnbs_37_20.
Rao, T. S. Sathyanarayana, i Chittaranjan Andrade. „Antidepressants and Sexual Dysfunction: Is Vortioxetine Among the Exceptions?” Journal of Psychosexual Health 4, nr 3 (2022): 155–56. https://doi.org/10.1177/26318318221116038.
Jacobsen, Paula L., Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, i Madhukar H. Trivedi. „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”. The Journal of Clinical Psychiatry 76, nr 5 (2015): 575–82. https://doi.org/10.4088/JCP.14m09335.
Jing, Elizabeth, i Kristyn Straw-Wilson. „Sexual Dysfunction in Selective Serotonin Reuptake Inhibitors (SSRIs) and Potential Solutions: A Narrative Literature Review”. The Mental Health Clinician 6, nr 4 (2016): 191–96. https://doi.org/10.9740/mhc.2016.07.191.
Polosan, Mircea, Marc Rabbani, Michael Cronquist Christensen, Kenneth Simonsen, i Hongye Ren. „Effectiveness of Vortioxetine in Patients with Major Depressive Disorder in Real-World Clinical Practice: French Cohort Results from the Global RELIEVE Study”. Neuropsychiatric Disease and Treatment 18 (2022): 1963–74. https://doi.org/10.2147/NDT.S374635.
Montejo, Angel L., Nieves Prieto, Rubén de Alarcón, Nerea Casado-Espada, Javier de la Iglesia, i Laura Montejo. „Management Strategies for Antidepressant-Related Sexual Dysfunction: A Clinical Approach”. Journal of Clinical Medicine 8, nr 10 (2019): 1640. https://doi.org/10.3390/jcm8101640.
Jing, Elizabeth, i Kristyn Straw-Wilson. „Sexual Dysfunction in Selective Serotonin Reuptake Inhibitors (SSRIs) and Potential Solutions: A Narrative Literature Review”. The Mental Health Clinician 6, nr 4 (2016): 191–96. https://doi.org/10.9740/mhc.2016.07.191.
Alvarez, Enric, Victor Perez, i Francesc Artigas. „Pharmacology and Clinical Potential of Vortioxetine in the Treatment of Major Depressive Disorder”. Neuropsychiatric Disease and Treatment 10 (2014): 1297–1307. https://doi.org/10.2147/NDT.S41387.
De Luca, Rosaria, Mirjam Bonanno, Alfredo Manuli, i Rocco Salvatore Calabrò. „Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study”. Medicines 9, nr 9 (2022): 45. https://doi.org/10.3390/medicines9090045.
Alvarez, Enric, Victor Perez, i Francesc Artigas. „Pharmacology and Clinical Potential of Vortioxetine in the Treatment of Major Depressive Disorder”. Neuropsychiatric Disease and Treatment 10 (2014): 1297–1307. https://doi.org/10.2147/NDT.S41387.
Abler, Birgit, Angela Seeringer, Antonie Hartmann, Georg Grön, Coraline Metzger, Martin Walter, i Julia Stingl. „Neural Correlates of Antidepressant-Related Sexual Dysfunction: A Placebo-Controlled fMRI Study on Healthy Males Under Subchronic Paroxetine and Bupropion”. Neuropsychopharmacology 36, nr 9 (2011): 1837–47. https://doi.org/10.1038/npp.2011.66.
De Luca, Rosaria, Mirjam Bonanno, Alfredo Manuli, i Rocco Salvatore Calabrò. „Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study”. Medicines 9, nr 9 (2022): 45. https://doi.org/10.3390/medicines9090045.
Sutar, Roshan, Faisal Siddiqui, i Abin Rajan. „Is Vortioxetine an Advantageous Choice for Erectile Dysfunction? A Case Report”. Journal of Psychosexual Health 2, nr 3–4 (2020): 281–83. https://doi.org/10.1177/2631831820973103.
Montejo, Angel L., Froilán Sánchez-Sánchez, Rubén De Alarcón, Juan Matías, Benjamin Cortés, Claudia Matos, Tomás Martín-Pinto, Peñitas Ríos, Nerea González-García, i José María Acosta. „Switching to Vortioxetine in Patients with Poorly Tolerated Antidepressant-Related Sexual Dysfunction in Clinical Practice: A 3-Month Prospective Real-Life Study”. Journal of Clinical Medicine 13, nr 2 (2024): 546. https://doi.org/10.3390/jcm13020546.
Alam, Mohammed Y., Paula L. Jacobsen, Yinzhong Chen, Michael Serenko, i Atul R. Mahableshwarkar. „Safety, Tolerability, and Efficacy of Vortioxetine (Lu AA21004) in Major Depressive Disorder: Results of an Open-Label, Flexible-Dose, 52-Week Extension Study”. International Clinical Psychopharmacology 29, nr 1 (2014): 36–44. https://doi.org/10.1097/YIC.0000000000000010.
Sutar, Roshan, Faisal Siddiqui, i Abin Rajan. „Is Vortioxetine an Advantageous Choice for Erectile Dysfunction? A Case Report”. Journal of Psychosexual Health 2, nr 3–4 (2020): 281–83. https://doi.org/10.1177/2631831820973103.
Kearns, Benjamin, Katy Cooper, Martin Orr, Munira Essat, Jean Hamilton, i Anna Cantrell. „The Incidence and Costs of Adverse Events Associated with Antidepressants: Results from a Systematic Review, Network Meta-Analysis and Multi-Country Economic Model”. Neuropsychiatric Disease and Treatment 18 (2022): 1133–43. https://doi.org/10.2147/NDT.S356414.
Citrome, L. „Vortioxetine for Major Depressive Disorder: A Systematic Review of the Efficacy and Safety Profile for This Newly Approved Antidepressant - What Is the Number Needed to Treat, Number Needed to Harm and Likelihood to Be Helped or Harmed?” International Journal of Clinical Practice 68, nr 1 (2014): 60–82. https://doi.org/10.1111/ijcp.12350.
Basson, Rosemary, i Thea Gilks. „Women’s Sexual Dysfunction Associated with Psychiatric Disorders and Their Treatment”. Women’s Health (London, England) 14 (2018): 1745506518762664. https://doi.org/10.1177/1745506518762664.
Kelliny, Marc, Paul E. Croarkin, Katherine M. Moore, i William V. Bobo. „Profile of Vortioxetine in the Treatment of Major Depressive Disorder: An Overview of the Primary and Secondary Literature”. Therapeutics and Clinical Risk Management 11 (2015): 1193–1212. https://doi.org/10.2147/TCRM.S55313.
Kearns, Benjamin, Katy Cooper, Martin Orr, Munira Essat, Jean Hamilton, i Anna Cantrell. „The Incidence and Costs of Adverse Events Associated with Antidepressants: Results from a Systematic Review, Network Meta-Analysis and Multi-Country Economic Model”. Neuropsychiatric Disease and Treatment 18 (2022): 1133–43. https://doi.org/10.2147/NDT.S356414.
Jacobsen, Paula L., Atul R. Mahableshwarkar, Michael Serenko, Serena Chan, i Madhukar H. Trivedi. „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”. The Journal of Clinical Psychiatry 76, nr 5 (2015): 575–82. https://doi.org/10.4088/JCP.14m09335.
Views:
73
Downloads:
3
Copyright (c) 2025 Mateusz Myśliwiec, Tytus Tyralik, Maciej Karwat, Julia Kular, Oliwia Malec, Justyna Niebylecka, Izabella Michalska, Natalia Glanc, Dominik Sendecki, Grzegorz Zalewski

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

