Skip to main navigation menu Skip to main content Skip to site footer

No. 2 (2024)

PRACTICE

Sexual Dysfunction during Antidepressant Treatment in Patients with Anxiety and Depressive Disorders (Implementation and Correction Algorithm)

https://doi.org/10.21265/PSYPH.2024.31.31.006

Published 2024-06-30

  • А.I. Salakhova
    • ,
  • M.I. Yagubov

А.I. Salakhova
Moscow Research Institute of Psychiatry — branch of the Serbsky National Medical Research Center for Psychiatry and Narcology of the Ministry of Health of the Russian Federation

M.I. Yagubov
Moscow Research Institute of Psychiatry — branch of the Serbsky National Medical Research Center for Psychiatry and Narcology of the Ministry of Health of the Russian Federation

Abstract

Relevance. This review article provides data describing the prevalence, clinical and pathogenetic features of sexual dysfunction (SD) during antidepressant (AD) therapy for patients with anxiety (AnxD) and depressive disorders (DD), comparative characteristics of ADs of various groups in relation to the risk of SD development, as well as methods for SD correction. Sexual dysfunction during AD therapy in patients with DD and AnxD can be associated with both the mental disorder itself and with the use of ADs, mainly selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs). The occurrence of SD may also be related to the age, gender and hormonal profile of the patient. When using SSRIs SD is observed in 70 % of cases, when using SNRIs and TCAs — in 40–45 % of cases and in less than 10 % of cases when taking ADs with a different mechanism of action. The severity of SD when taking ADs is dose-dependent and may vary depending on the effect on neurotransmitters (serotonin, norepinephrine, dopamine), induction of prolactin release from the pituitary gland, anticholinergic side effects, inhibition of nitric oxide synthesis and characteristics of sexual life. As the use of most ADs can lead to SD, it is advisable to assess the patient’s sexual function (SF) using specialized questionnaires in order to select ADs that are more favourable to SF.

Methods. The review is based on 1 meta-analysis, 6 systematic reviews, 18 reviews, 7 randomized controlled trials, 20 studies including cross-sectional, parallel, prospective, retrospective, blinded and open-label studies, 1 monograph and 1 national psychiatric guideline published from 2017 to January 2024. Data search was carried out using titles, abstracts and keywords sexual dysfunction, antidepressants, depressive disorder, anxiety disorder in the Elibrary and PubMed databases. Inclusion criteria were publications reporting an association of SD with any AD medication, as well as with AnxD or DD. Exclusion criteria were results from preclinical studies. The initial screening retrieved 368 publications from peer-reviewed scientific journals with different study designs. Publications that did not meet the inclusion criteria were excluded.

Results. Based on an analysis of 55 scientific literature sources, it was found that SSRIs have the most pronounced negative effect on SF. ADs, according to the degree of their negative impact on SF and the frequency of occurrence of SD, are arranged in descending order as follows: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, duloxetine, escitalopram, fluvoxamine, mirtazapine, agomelatine, moclobemide. However, there are conflicting data in some sources. For example, according to one systematic review, the incidence of SD when taking fluvoxamine exceeded the incidence of SD when using fluoxetine, which contradicted data from other studies. A similar contradiction is found in data from an open comparative study, which indicates that SD occurs more often when taking fluvoxamine than when taking sertraline. According to the studies analyzed in the review, agomelatine, mirtazapine, moclobemide, trazodone, mianserin and vortioxetine, due to their beneficial effect on SF, can be prescribed as drugs of choice in the presence of SD before the start of AD therapy, and as an “antidote” in cases of SD occurrence during AD therapy. The leading factor contributing to SD is the neurotransmitter serotonin. Its inhibitory activity is primarily due to the activation of 5-HT2 and 5-HT3 receptors, which leads to a change in sexual response, decreased sexual desire and delayed orgasm, including through inhibition of the spinal ejaculation center. In addition, serotonin, acting on the autonomic nervous system, including the parasympathetic — affects erection and clitoral arousal, and the sympathetic — affects orgasm and ejaculation.

Conclusion. Based on the literature review, an algorithm for the management of patients with AnxD and DD, suffering from SD, and in need for AD therapy has been proposed, which will enable a psychiatrist to identify SD at different stages of AD therapy, take measures to correct it, thereby improving the quality of life of patients and their adherence to treatment.

Keywords

sexual dysfunction, antidepressants, depressive disorder, anxiety disorder

PDF (Русский)

References

  1. Santomauro D.F., Mantilla Herrera Ana M., Shadid J. et al. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic // Lancet. – 2021. – Vol. 398 (10312). – Pp. 1700–1712. – https://doi.org/10.1016/S0140-6736(21)02143-7
  2. Herder T., Spoelstra S.K., Peters A.W.M. et al. Sexual dysfunction related to psychiatric disorders: a systematic review // The Journal of Sexual Medicine. – 2023. – Vol. 20 (7). – Pp. 965–976. – https://doi.org/10.1093/jsxmed/qdad074
  3. Montejo A.L., Montejo L., Baldwin D.S. The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management // World Psychiatry. – 2018. – Vol. 17 (1). – Pp. 3–11. – https://doi.org/10.1002/wps.20509
  4. Kennedy S.H., Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants // Journal of Clinical Psychopharmacology. – 2009. – Vol. 29 (2). – Pp. 157–164. – https://doi.org/10.1097/JCP.0b013e31819c76e9
  5. Мосолов С.Н. Тревожные и депрессивные расстройства: коморбидность и терапия. – М.: Артинфо Паблишинг, 2007. – 64 с.
  6. AlBreiki M., AlMaqbali M., AlRisi K. et al. Prevalence of antidepressant-induced sexual dysfunction among psychiatric outpatients attending a tertiary care hospital // Neurosciences (Riyadh, Saudi Arabia). – 2020. – Vol. 25 (1). – Pp. 55–60. – https://doi.org/10.17712/nsj.2020.1.20190058
  7. Alizadeh A., Farnam F., Raisi F. et al. Prevalence of and Risk Factors for Genito-Pelvic Pain/Penetration Disorder: A Population-Based Study of Iranian Women // The Journal of Sexual Medicine. – 2019 – Vol. 16 (7). – Pp. 1068–1077. – https://doi.org/10.1016/j.jsxm.2019.04.019
  8. Reisman Y. Post-SSRI sexual dysfunction // BMJ. – 2020. – Vol. 368 (754). – Pp. 1–2. – https://doi.org/10.1136/bmj.m754
  9. Montejo A., Calama J., Rico-Villademoros F. et al. A real-world study on antidepressant-associated sexual dysfunction in 2144 outpatients: The salsex I study // Archives of sexual behavior. – 2019. – Vol. 48 (3). – Pp. 923–933. – https://doi.org/10.1007/s10508-018-1365-6
  10. Jacobsen P.L., Nomikos G.G., Zhong W. et al. Clinical implications of directly switching antidepressants in well-treated depressed patients with treatment-emergent sexual dysfunction: a comparison between vortioxetine and escitalopram // CNS Spectrums. – 2020. – Vol. 25 (1). – Pp. 50–63. – https://doi.org/10.1017/S1092852919000750
  11. Serretti A., Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis // Journal of Clinical Psychopharmacology. – 2009. – Vol. 29 (3). – Pp. 259–266. – https://doi.org/10.1097/JCP.0b013e3181a5233f
  12. Reichenpfader U., Gartlehner G., Morgan L.C. 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 Safety. – 2014. – Vol. 37 (1). – Pp. 19–31. – https://doi.org/10.1007/s40264-013-0129-4
  13. Lew-Starowicz M., Giraldi A. Impact of psychotropic medications on sexual functioning // Lew-Starowicz M., Giraldi A. Psychiatry and sexual medicine, a comprehensive guide for clinical practitioners. – Cham: Springer, 2021. – Art. 358. – https://doi.org/10.1007/978-3-030-52298-8
  14. Baldwin D.S., Manson C, Nowak M. Impact of antidepressant drugs on sexual function and satisfaction // CNS Drugs. – 2015. – Vol. 29 (11). – Pp. 905–913. – https://doi.org/10.1007/s40263-015-0294-3
  15. Hutters C.L., Giraldi A. Sexual side effects from treatment with SSRI // Ugeskrift for Laeger. – 2022. – Vol. 184 (7A). – Pp. 708–711. – Available at: https://ugeskriftet.dk/videnskab/seksuelle-bivirkninger-ved-ssri (accessed March 23, 2024).
  16. Ashton A.K., Jamerson B.D., Weinstein W.L. et al. Antidepressant-related adverse effects impacting treatment compliance: Results of a patient survey // Current Therapeutic Research, Clinical and Experimental. – 2005. – Vol. 66 (2). – Pp. 96–106. – https://doi.org/10.1016/j.curtheres.2005.04.006
  17. Winter J., Curtis K., Hu B. et al. Sexual dysfunction with major depressive disorder and antidepressant treatments: Impact, assessment, and management // Expert Opinion on Drug Safety. – 2022. – Vol. 21 (7). – Pp. 913–930. – https://doi.org/10.1080/14740338.2022.2049753
  18. Chen L.W., Chen M.Y., Lian Z.P. et al. Amitriptyline and sexual function: A Systematic review updated for sexual health practice // American Journal of Men’s Health. – 2018. – Vol. 12 (2). – Pp. 370–379. – https://doi.org/10.1177/1557988317734519
  19. La Torre A, Giupponi G, Duffy D et al Sexual dysfunction related to psychotropic drugs: a critical review – Part I: Antidepressants // Pharmacopsychiatry. – 2013. – Vol. 46 (5). – Pp. 191–199. – https://doi.org/10.1055/s-0033-1345205
  20. Monteiro W.O., Noshirvani H.F., Marks I.M. et al. Anorgasmia from clomipramine in obsessive-compulsive disorder. A controlled trial // The British Journal of Psychiatry: The Journal of Mental Science. – 1987. – Vol. 151. – Pp. 107–12. – https://doi.org/10.1192/bjp.151.1.107
  21. Waldinger M.D., Zwinderman A.H., Olivier B. On-demand treatment of premature ejaculation with clomipramine and paroxetine: A randomized, double-blind fixed-dose study with stopwatch assessment // European Urology. – 2004. – Vol. 46 (4). – Pp. 510–516. – https://doi.org/10.1016/j.eururo.2004.05.005
  22. Philipp M., Tiller J.W., Baier D. et al. Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults. The Australian and German Study Groups // European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. – 2000. – Vol. 10 (5). – Pp. 305–314. – https://doi.org/10.1016/s0924-977x(00)00085-7
  23. Bala A., Nguyen H.M.T, Hellstrom W.J.G. Post-SSRI sexual dysfunction: A literature review // Sexual Medicine Reviews. – 2018 – Vol. 6 (1). – Pp. 29–34. – https://doi.org/10.1016/j.sxmr.2017.07.002
  24. Trinchieri M., Trinchieri M., Perletti G. et al. Erectile and ejaculatory dysfunction associated with use of psychotropic drugs: A systematic review // The Journal of Sexual Medicine. – 2021. – Vol. 18 (8). – Pp. 1354–1363. – https://doi.org/10.1016/j.jsxm.2021.05.016
  25. Clayton A.H., Pradko J.F., Croft H.A. et al. Prevalence of sexual dysfunction among newer antidepressants // The Journal of Clinical Psychiatry. – 2002 – Vol. 63 (4). – Pp. 357– 366. – https://doi.org/10.4088/jcp.v63n0414
  26. Michael A. Venlafaxine-induced painful ejaculation // The British Journal of Psychiatry: The Journal of Mental Science. – 2000. – Vol. 177. – Art. 282. – https://doi.org/10.1192/bjp.177.3.282-b
  27. Karakurt F., Kargili A., Uz B.et al. Venlafaxine-induced gynecomastia in a young patient: a case report // Clinical Neuropharmacology. – 2009. – Vol. 32 (1). – Pp. 51–52. – https://doi.org/10.1097/WNF.0B013E3181679126
  28. Bhatia S.C., Bhatia S.K., Bencomo L. Effective treatment of venlafaxine-induced noncyclical mastalgia with bromocriptine // Journal of Clinical Psychopharmacology. – 2000. – Vol. 20 (5). – P. 590–591. – https://doi.org/10.1097/00004714-200010000-00024
  29. Sternbach H. Venlafaxine-induced galactorrhea // Journal of Clinical Psychopharmacology. – 2003. – Vol. 23 (1). – Pp. 109–110. – https://doi.org/10.1097/00004714-200302000-00023
  30. Berilgen M.S. Late-onset galactorrhea and menometrorrhagia with venlafaxine use in a migraine patient // Journal of Clinical Psychopharmacology. – 2010. – Vol. 30 (6). – Pp. 753–754. – https://doi.org/10.1097/JCP.0b013e3181fc327f
  31. Montejo A., Prieto N., Alarcón R. et al. Management strategies for antidepressant-related sexual dysfunction: A clinical approach // Journal of Clinical Medicine. – 2019. – Vol. 8 (10). – Art. 1640. – https://doi.org/10.3390/jcm8101640
  32. Gelenberg A.J., Dunner D.L., Rothschild A.J. et al. Sexual functioning in patients with recurrent major depressive disorder enrolled in the PREVENT study // The Journal of Nervous and Mental Disease. – 2013. – Vol. 201 (4). – Pp. 266–273. – https://doi.org/10.1097/NMD.0b013e318288d298
  33. Ben-Sheetrit J., Aizenberg D., Csoka AB. et al. Post-SSRI Sexual Dysfunction: Clinical characterization and preliminary assessment of contributory factors and dose-response relationship // Journal of Clinical Psychopharmacology. – 2015. – Vol. 35 (3). – Pp. 273– 278. – https://doi.org/10.1097/JCP.0000000000000300
  34. Atmaca M. Selective serotonin reuptake inhibitor-induced sexual dysfunction: Current Management Perspectives // Neuropsychiatric Disease and Treatment. – 2020 – Vol. 16. – Pp. 1043–1050. – https://doi.org/10.2147/NDT.S185757
  35. Atmaca M., Korkmaz S., Topuz M. et al. Mirtazapine augmentation for selective serotonin reuptake inhibitor-induced sexual dysfunction: A retrospective investigation // Psychiatry Investigation. – 2011. – Vol. 8 (1). – Pp. 55–57. – https://doi.org/10.4306/pi.2011.8.1.55
  36. Osvath P., Fekete S., Voros V. et al. Mirtazapine treatment and sexual functions: results of a Hungarian, multicentre, prospective study in depressed out-patients // International Journal of Psychiatry in Clinical Practice. – 2007. – Vol. 11 (3). – Pp. 242–245. – https://doi.org/10.1080/13651500701241147
  37. Ozmenler N.K., Karlidere T., Bozkurt A. et al. Mirtazapine augmentation in depressed patients with sexual dysfunction due to selective serotonin reuptake inhibitors // Human Psychopharmacology. – 2008. – Vol. 23 (4). – Pp. 321–326. – https://doi.org/10.1002/hup.929
  38. Aizenberg D., Gur S., Zemishlany Z. et al. Mianserin, a 5-HT (2a/2c) and α2 antagonist, in the treatment of sexual dysfunction induced by serotonin reuptake inhibitors // Clinical Neuropharmacology. – 1997. – Vol. 20 (3). – Pp. 210–214. – https://doi.org/10.1097/00002826-199706000-00004
  39. Aizenberg D., Naor S., Zemishlany Z. et al. The serotonin antagonist mianserin for treatment of serotonin reuptake inhibitor-induced sexual dysfunction in women: An open-label add-on study // Clinical Neuropharmacology. – 1999. – Vol. 22 (6). – Pp. 347–350. – Available at: https://pubmed.ncbi.nlm.nih.gov/10626096/ (accessed March 24, 2024).
  40. Cheng W-M., Lin T-P., Lin A.T.L. et al. A nationwide population study of trazodone use in urology patients // Journal of the Chinese Medical Association: JCMA. – 2013. – Vol. 76. – Pp. 432–437. – https://doi.org/10.1016/j.jcma.2013.05.002
  41. Bossini L., Casolaro I., Koukouna D. et al. Off-label uses of trazodone: a review // Expert Opinion on Pharmacotherapy. – 2012. – Vol. 13 (12). – Pp. 1707–1717. – https://doi.org/10.1517/14656566.2012.699523
  42. Enzlin P., Vanderschueren D., Bonte L. et al. Trazodone: a double-blind, placebo-controlled, randomized study of its effects in patients with erectile dysfunction without major organic findings // International Journal of Impotence Research. – 2000. – Vol. 12 (4), – Pp. 223–228. – https://doi.org/10.1038/sj.ijir.3900550
  43. Berner M. Psychopharmakaassoziierte sexuelle Funktionsstörungen und ihre Behandlung [Sexual dysfunction associated with psychotropic drugs and treatment options] // Der Nervenarzt – 2017. – Vol. 88 (5). – Pp. 459–465. – https://doi.org/10.1007/s00115-017-0307-1
  44. Stryjer R., Spivak B., Strous R.D. et al. Trazodone for the treatment of sexual dysfunction induced by serotonin reuptake inhibitors: a preliminary open-label study // Clinical Neuropharmacology. – 2009. – Vol. 32 (2). – Pp. 82–84. – https://doi.org/10.1097/WNF.0B013E31816D1CDC
  45. Mann K., Pankok J., Leissner et al. Effects of moclobemide on sexual performance and nocturnal erections in psychogenic erectile dysfunction // Psychopharmacology. – 2001. – Vol. 156 (1). – Pp. 86–91. – https://doi.org/10.1007/s002130100717
  46. Lorenz T.A, Meston C.M. Exercise improves sexual function in women taking antidepressants: results from a randomized crossover trial // Depression and Anxiety. – 2014. – Vol. 31 (3). – Pp. 188–195. – https://doi.org/10.1002/da.22208
  47. Кибрик Н.Д., Ягубов М.И. Сексуальная дисфункция, не обусловленная органическими болезнями // Психиатрия. Национальное руководство / под ред. Н.Г. Незнанова, Ю.А. Александровского. – М.: ГЭОТАР-Медиа, 2018. – 1891 с. – С. 1247–1289.
  48. Nurnberg H.G., Hensley P.L., Heiman J.R. et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: A randomized controlled trial // JAMA. – 2008. – Vol. 300 (4). – Pp. 395–404. – https://doi.org/10.1001/jama.300.4.395
  49. Fooladi E., Bell R.J., Jane F. et al. Testosterone improves antidepressant-emergent loss of libido in women: findings from a randomized, double-blind, placebo-controlled trial // The Journal of Sexual Medicine. – 2014. – Vol. 11 (3). – Pp. 831–839. – https://doi.org/10.1111/jsm.12426
  50. Clayton A.H., El Haddad S., Iluonakhamhe J.P. et al. Sexual dysfunction associated with major depressive disorder and antidepressant treatment // Expert opinion on drug safety. – 2014. – Vol. 13 (10). – Pр. 1361–1374. – https://doi.org/10.1517/14740338.2014.951324
  51. Pfaus J.G. Pathways of sexual desire // The journal of sexual medicine. – 2009. – Vol. 6 (6). – P. 1506-33. – https://doi.org/10.1111/j.1743-6109.2009.01309.x
  52. Serretti A., Chiesa A. Sexual side effects of pharmacological treatment of psychiatric diseases // Clinical pharmacology and therapeutics. – 2011. – Vol. 89 (1). – Pр. 142-147. – https://doi.org/10.1038/clpt.2010.70
  53. Rappek N.A. M., Sidi H., Kumar J. et al. Serotonin Selective Reuptake Inhibitors (SSRIs) and Female Sexual Dysfunction (FSD): Hypothesis on its Association and Options of Treatment // Current drug targets. – 2018. – Vol. 19 (12). – Pр. 1352–1358. – https://doi.org/10.2174/1389450117666161227142947
  54. Drobnis E.Z., Nangia A.K. Psychotropics and Male Reproduction // Impacts of Medications on Male Fertility. Advances in Experimental Medicine and Biology. Cham: Springer International Publishing, 2017. – Pр. 63-81. – https://doi.org/10.1007/978-3-319-69535-8_8
  55. Clayton A. Changes in Sexual Functioning Questionnaire (CSFQ). – 1998. – URL: https://www.dbsalliance.org/wp-content/uploads/2019/02/ Restoring_Intimacy_CSFQ_Handout.pdf
  56. McGahuey C.A., Gelenberg A.J., Laukes C.A. et al. The Arizona Sexual Experience Scale (ASEX): reliability and validity // Journal of Sex & Marital Therapy. – 2000. – Vol. 26 (1). – P. 39–40. – https://doi.org/10.1080/009262300278623
  57. Clayton A.H., Alkis A.R., Parikh N.B., et al. Sexual Dysfunction Due to Psychotropic Medications // The Psychiatric clinics of North America. – 2016. – Vol. 39 (3). – Pр. 427–463. – https://doi.org/10.1016/j.psc.2016.04.006

Downloads

Download data is not yet available.