Prevalence of antidepressant-induced sexual dysfunction among psychiatric outpatients attending a tertiary care hospital ======================================================================================================================== * Mohammed AlBreiki * Mandher AlMaqbali * Khalid AlRisi * Hamed AlSinawi * Maryam Al Balushi * Wedad Al Zakwani ## Abstract **Objectives:** To measure the prevalence of sexual dysfunction in psychiatric outpatients treated with fluoxetine, paroxetine, venlafaxine or mirtazapine. **Methods:** This is a retrospective cross-sectional study conducted in Sultan Qaboos University Hospital, Muscat, Oman. All patients above 18 years of age, attending psychiatric clinic and taking fluoxetine, paroxetiene, venlafaxine or mirtazapine for various indications were invited to participate in the study. A data collection sheet was designed to document the patients’ demographic features, psychiatric diagnosis, type, dose and duration of antidepressant treatment. Sexual side effects’ part of Toronto Side Effect Scale (TSES) was used to assess the presence of sexual dysfunction. **Results:** A total of 137 patients (Male: 51%, Female: 49%) were included in the study. The mean age for the participants was 38 years (range: 19-72 years). The number of patients for each antidepressant was as follows: paroxetine (52 patients), fluoxetine (36), mirtazapine (36 patients) and venlafaxine (17 patients). The average duration of the antidepressant use was 3.9 years. The overall prevalence of sexual dysfunction was 39%. Paroxetine was the most common antidepressant associated with sexual dysfunction especially for decreased libido (59.6%) and delayed ejaculation (34.4%). In contrary, mirtazapine was the lowest among antidepressants to cause sexual dysfunction. **Conclusion:** Sexual dysfunction is common among patients treated with antidepressants particularly selective serotonin reuptake inhibitors (SSRIs). Addressing this side effects early in treatment can improve compliance to treatment and prevent relapse. Depression is one of the most common morbidities worldwide.1 People with depression can experience limitations in their daily activities.1 In 2017, major depressive disorder was considered as the third most common morbidity worldwide.2 The use of antidepressants reduces the rates of morbidity and mortality associated with depression.3 Several side effects have been linked to the use of antidepressants.4 One of the most common side effects of antidepressants is sexual dysfunction.5-7 Additionally, sexual dysfunction has been noted to be related to other risk factors including depression itself, other psychosocial factors, general medical illness, psychiatric disorders and some other medications.4,8 Patients experiencing antidepressant-induced sexual side effects usually under-report their symptoms.9-12 Sexual dysfunction has various clinical manifestations and may present differently between males and females. In males, it presents as a decreased libido, difficulty in sustaining erection, anorgasmia, and delayed ejaculation.7,12-14 In females, it presents as a decrease in sexual desire, impaired arousal and lubrication, and delayed orgasm.10 Worsham et al7(2018) reported that 32% of European patients taking antidepressants experience sexual dysfunction side effects. In another study (Balon 1993),15 43% of participants expressed having at least one sexual dysfunction symptom after taking antidepressants.In a multicentre descriptive study involving 344 patients, it was found that 61% of males and 52% of females reported having sexual dysfunction side effects.16 Sexual dysfunction can affect the patient’s quality of life and reduce their compliance to taking the antidepressant treatment.7,12,14,17,18 The risk of experiencing symptoms of sexual dysfunction following antidepressant treatment varies between the different classes of antidepressants and, more specifically, among antidepressants in the same class. Selective serotonin reuptake inhibitors (SSRIs), especially paroxetine, clomipramine and venlafaxine, are the most common antidepressants known to cause sexual dysfunction.12,13,19,20 This study aimed to examine the prevalence of sexual side effects among patients taking antidepressants attending the psychiatry clinic at Sultan Qaboos University Hospital; correlate the onset of antidepressant-induced sexual dysfunction with the patients’ age, gender, diagnosis, duration of treatment and type of antidepressant used; indicate the rate of antidepressant-induced sexual dysfunction from four antidepressants commonly prescribed in Oman; and will set a platform for future studies examining specific side effects. ## Methods This was a cross-sectional study conducted in the psychiatry clinic at Sultan Qaboos University Hospital (SQUH). All patients above 18 years of age attending the clinic from October 2017 to April 2018 were checked for their eligibility to participate in this study. All patients with a documented mental health disorder who were taking antidepressant medications and were being treated in the outpatient clinic within the dates specified were included. The antidepressants which were focused on in this study were: fluoxetine, paroxetine, venlafaxine and mirtazapine. Ethical approval was obtained from the Medical Research and Ethics Committee (MREC) at Sultan Qaboos University and the study adhered to the Declaration of Helsinki (1964), which sets the standards for medical research on human subjects. A written consent from all participants was obtained after the study was explained to them. Patients were selected using systematic random sampling, and every third patient who attended the psychiatry clinic was invited to participate in the study. A psychiatric nurse invited the patients to participate in this study, explained the aims of the study, obtained the patient’s consent and distributed the questionnaires. For illiterate patients, the information was collected by the nurse following a verbal explanation of all of the questions. Medical records were then used to verify the information given by the participants. Sample size was calculated with the help of sample calculating website (www.surveysystem.com/sscalc.htm), taking into consideration the total number of patients attending SQUH psychiatric outpatient clinic, with a confidence interval (CI) of 95%. A data collection sheet was used to collect the patients’ demographics and to record the patient’s diagnosis, duration of treatment, antidepressant used and presence of psychiatric or medical comorbidities. The patients’ mental health disorder diagnosis was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Patients were excluded if they declined to sign a written consent form and when their clinical presentation was not consistent with DSM-5 criteria for any mental health disorder. ### Assessment tool The Toronto Side Effects Scale (TSES) was used to measure the side effects of the antidepressants included in the study. The TSES is a clinician-administered antidepressant side effects scale developed by Vanerdkooy and his colleagues in 2002. This scale rates the frequency and severity of 32 side effects from 3 major areas which are affected by antidepressants’ side effects: central nervous system, gastrointestinal system and sexual functions. This study concentrated only on the sexual side effects portion of the scale. The scale was a useful tool to measure antidepressant side effects.21 ### Data management Data analysis was done using the Statistical Package for the Social Sciences (SPSS) version 22 (IBM Corp., Armonk, NY, USA). Categorized variables were described as percentages with confidence intervals (CIs). Continuous variables were presented as means with standard deviation (SD) or medians with inter-quartile range. To assess the relationships between the variables a univariate analysis Chi-square test, the t-test and analysis of variance (ANOVA) were used. ## Results The total number of patients who participated in the study was 137 (male: 49%, female: 51%). The average age of the participants was 38-years-old (range: 19-72 years). Most of the participants were married (67.8%), non-smokers (96%), did not drink alcohol (99%) and had no medical comorbidity (93.5%). Major depressive disorder was the most common diagnosis among the participants (45%), followed by anxiety disorders (36%) and obsessive compulsive disorder (15.3%). **Table 1** summarizes the patient demographic data and the frequency of the various diagnoses. View this table: [Table 1](http://nsj.org.sa/content/25/1/55/T1) Table 1 Patients’ demographic characteristics. Among the participants of this study, 38.0% were taking paroxetine, 26.3% fluoxetine, while 23.4% used mirtazapine and 12.4% took venlafaxine. The mean duration of antidepressant use and the average dosage can be found in **Table 2**. View this table: [Table 2](http://nsj.org.sa/content/25/1/55/T2) Table 2 Antidepressants usage, average doses and mean duration of use for the participants in this study. The overall prevalence of sexual dysfunction among the participants of this study was 39.1%, with more than third of the participants experienced at least one sexual side effect from the antidepressants. Among the male participants, delayed ejaculation, premature ejaculation and erectile dysfunction were reported in 29.0%, 55.6% and 40.0% respectively. Decreased libido was reported by 45.0% of all participants, while 40.0% experienced anorgasmia following the use of antidepressants. Male participants reported increased and decreased libido, as well as anorgasmia, more frequently than the female participants, although the difference was only noted to be statistically significant (*p* < 0.05) - using univariate analysis Chi square test - for increased libido. **Table 3** compares the percentages of decreased libido, increased libido and anorgasmia between the male and female participants in this study. View this table: [Table 3](http://nsj.org.sa/content/25/1/55/T3) Table 3 Comparison of the percentages of decreased libido, increased libido and anorgasmia between the male and female participants in this study. Using univariate analysis Chi square test, there were no statistical differences in the onset of sexual dysfunction between the age groups. Of the participants using antidepressant therapy for more than one year, 42.6% of them experienced adverse sexual side effects. In contrast, only 23.6% of participants reported adverse sexual side effects after using antidepressants for less than a year. Of the 4 antidepressants observed in this study, paroxetine was found to cause the highest rate of decreased libido (59.60%) and delayed ejaculation (34.44%) mong all participants. Venlafaxine and paroxetine were associated with erectile dysfunction, anorgasmia and premature ejaculation more frequently than mirtazapine and fluoxetine. With regards to the onset of the sexual dysfunction between all of the antidepressants, there was no statistically significant difference. **Table 4** shows the rate of each sexual side effect for each antidepressant. View this table: [Table 4](http://nsj.org.sa/content/25/1/55/T4) Table 4 Rate (w%) of sexual dysfunction among participants per antidepressant. ## Discussion Due to several socio-cultural factors, studies relating to sexual health are uncommon in Oman. This study was conducted in a tertiary care hospital in Muscat, which receives referrals from all areas of Oman. Therefore, this study’s population should represent people from all of the Omani governates. The antidepressants included in this study were selected based on findings from a pharmacy audit, indicating that these were the four most commonly prescribed antidepressants in the psychiatry clinic of SQUH. As part of the patient screening, inquiries about the sexual functions of all participants were made to ensure that the sexual dysfunction was due to the antidepressant treatment. In the present study, more than a third of participants (39.1%) reported to have at least one sexual dynsfunction symptom following the use of antidepressants. This finding is consistent with many previous studies which have found that a significant number of patients complained of sexual dysfunction following antidepressant treatment.22,23 One study, by Lee et al (2010)23 found that 46.5% of patients attending a metal health clinic suffered from sexual dysfunction after taking antidepressant. Montejo et al12 examined 1022 patients in multiple centres around Spain and found that more than half of the participants (59.1%) experienced sexual dysfunction after being prescribed antidepressants. This study found that the rate and type of sexual dysfunction varied depending on the antidepressant. For example; paroxetine was associated with a higher incidence of decreased libido and delayed ejaculation as compared to other antidepressants. Patients taking mirtazapine and fluoxetine reported less sexual dysfunction than those on paroxetine and venlafaxine. These findings replicate the results of other similar studies, which showed that paroxetine was linked to a higher frequency of sexual dysfunction.12,23,24 Paroxetine causes higher rates of sexual dysfunction due to its mechanism of action, as paroxetine blocks D2-receptors which have been found to be directly involved in the sexual functions of animals. Moreover, it inhibits the synthesis of nitric oxide which is essential for erections.25,26 The reason that mirtazapine is less likely to cause sexual dysfunction is also related to its unique mechanism of action. Mirtazapine blocks 5-HT2 and 5-HT3, which have been associated with fewer sexual side effects and the ability to promote orgasm.12 Sexual side effects following antidepressant therapy usually appear in the early stages of the treatment. This is especially true for paroxetine, which often causes decreased libido and erectile dysfunction in the first month of therapy.27 However, in this study patients who used antidepressant medication for more than one year experienced more sexual dysfunction than patients who used it for less than 1 year. This may be attributed to the fact that most patients who experience sexual dysfunction discontinue their medication early in the treatment or switch to another medication less likely to cause sexual side effects. Moreover, it may be related to specific ethnic variations which can affect the pharmacokinetic nature of the antidepressants and results in a prolonged discrepancy between prescribing the antidepressant and the onset of the side effects.28 However, this needs further exploration by future researches. It is imperative to address the sexual side effects of antidepressants during patients’ follow-up appointments. Several studies have shown that treatment non-compliance is common among patients who experience sexual dysfunction following antidepressant treatment.24 This results in treatment failure and recurrence of depressive symptoms. Furthermore, sexual dysfunction after antidepressant therapy was found to have a direct negative impact on patient self-esteem and their quality of the life, and can also impact their relationship with a sexual partner.29 ### Limitations The sample size for this study is relatively small when divided across the 4 antidepressants involved in this study. Moreover, some patients may under-report sexual side effects due to the sensitivity of this issue in the Arabic culture. This may affects the numbers representing the prevalence of sexual side effects when compared to other cultures. ### Conclusions Sexual side effects are common among patients who are being treated with antidepressant medications. Paroxetine and venlafaxine were found to be associated with an increased risk of sexual dysfunction as compared to fluoxetine and mirtazapine. Addressing patients’ sexual dysfunctions early on in their treatment can improve patient compliance to treatment and prevent relapse. Student Corner We invite students from a variety of medical disciplines to submit original contributions based on their supervised research. The Student Corner of Saudi Med J aims to help students explore research opportunities and network with other peers and mentors in the same field. Submission Guidelines Submitted Abstracts should include the following: • Title should be descriptive • Author’s names and affiliation(specify college level/year, academic degree of Senior Author) • Abstract must be structured and not more than 300 words • The following are the typical headings: Objectives (background, why the study was done, specific aims) Methods (setting, date of study, design, subjects, intervention and analysis) Results (findings, data and statistical tests) and Conclusion (general interpretation of results) General Information on Abstract Submission Submitted Abstracts should be co-authored by a Senior Supervisor Abstracts will be reviewed by Student’s Corner Section Editor There is no fee to submit an Abstract Ethical Approval should be provided Non-indexed materials ## Footnotes * **Disclosure.** Authors have no conflict of interests, and the work was not supported or funded by any drug company. * Received July 12, 2019. * Accepted November 26, 2019. * Copyright: © Neurosciences Neurosciences is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. ## References 1. Silva MT, Galvao TF, Martins SS, Pereira MG, Silva MT, Galvao TF, et al. (2014) Prevalence of depression morbidity among Brazilian adults: a systematic review and meta-analysis. Braz J Psychiatry 36, 262–270. 2. Lancet T (2018) GBD 2017: a fragile world. The Lancet 392, 1683. 3. Angst F, Stassen HH, Clayton PJ, Angst J (2002) Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord 68, 167–181. 4. Ferguson JM (2001) The effects of antidepressants on sexual functioning in depressed patients: A review. J Clin Psychiatry 62, 22–34. 5. Montgomery SA, Baldwin DS, Riley A (2002) Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. J Affect Disord 69, 119–140. 6. Torre AL, Giupponi G, Duffy D, Conca A (2013) Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review - Part I: Antidepressants. Pharmacopsychiatry 46, 191–199. 7. Worsham J, Bishop JR, Ellingrod VL (Jan, 2007) Antidepressant Associated Sexual Dysfunction: A Review. Journal of College of Psychiatric and Neurological Pharmacists. 8. Clayton AH, Montejo AL (2006) Major depressive disorder, antidepressants, and sexual dysfunction. J Clin Psychiatry 67, 33–37. 9. Chokka PR, Hankey JR (2018) Assessment and management of sexual dysfunction in the context of depression. Ther Adv Psychopharmacol 8, 13–23. 10. Sreelakshmy K, Velayudhan R, Kuriakose D, Nair R, Sreelakshmy K, Velayudhan R, et al. (2017) Sexual dysfunction in females with depression: a cross-sectional study. Trends Psychiatry Psychother 39, 106–109. 11. Serretti A, Chiesa A (2009) Treatment-Emergent Sexual Dysfunction Related to Antidepressants: A Meta-Analysis. J Clin Psychopharmacol 29, 259. 12. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F (2001) Incidence or sexual dysfunction associated with antidepressant agents: A prospective multicenter study of 1022 outpatients. J Clin Psychiatry 62, 10–21. 13. Hsu JH, Shen WW (1995) Male Sexual Side Effects Associated with Antidepressants: A Descriptive Clinical Study of 32 Patients. Int J Psychiatry Med 25, 191–201. 14. Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM (2000) Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 61, 276–281. 15. Balon R, Yeragani VK, Pohl R, Ramesh C (1993) Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 54, 209–212. 16. Montejo-González AL, Llorca G, Izquierdo JA, Ledesma A, Bousoño M, Calcedo A, et al. (1997) SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 23, 176–194. 17. Rosenberg KP, Bleiberg KL, Koscis J, Gross C (2003) A Survey of Sexual Side Effects Among Severely Mentally Ill Patients Taking Psychotropic Medications: Impact on Compliance. J Sex Marital Ther 29, 289–296. 18. Segraves RT (1998) Antidepressant-induced sexual dysfunction. J Clin Psychiatry 59, 48–54. 19. Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C, et al. (2002) Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 63, 357–366. 20. Waldinger MD, Olivier B (1998) Selective serotonin reuptake inhibitor-induced sexual dysfunction: clinical and research considerations. Int Clin Psychopharmacol 13, Suppl 6, S27–S33. 21. Vanderkooy JD, Kennedy SH, Michael RM (2002) Antidepressant Side Effects in Depression Patients Treated in a Naturalistic Setting: A Study of Bupropion, Moclobemide, Paroxetine, Sertraline, and Venlafaxine. Can J Psychiatry 47, 174–180. 22. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F (2001) 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 62, Suppl 3, 10–21. 23. Lee KU, Lee YM, Nam JM, Lee HK, Kweon YS, Lee CT, et al. (2010) Antidepressant-Induced Sexual Dysfunction among Newer Antidepressants in a Naturalistic Setting. Psychiatry Investig 7, 55–59. 24. Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM (2002) Antidepressant-induced sexual dysfunction. Ann Pharmacother 36, 1577–1589. 25. Stahl SM (2001) The psychopharmacology of sex, Part 1: Neurotransmitters and the 3 phases of the human sexual response. J Clin Psychiatry 62, 80–81. 26. Angulo J, Peiró C, Sanchez-Ferrer CF, Gabancho S, Cuevas P, Gupta S, et al. (2001) Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue. Br J Pharmacol 134, 1190–1194. 27. Goldstein BJ, Goodnick PJ (1998) Selective serotonin reuptake inhibitors in the treatment of affective disorders--III. Tolerability, safety and pharmacoeconomics. J Psychopharmacol 12, S55–S87. 28. Chaudhry I, Neelam K, Duddu V, Husain N (2008) Ethnicity and psychopharmacology. J Psychopharmacol 22, 673–680. 29. Williams VS, Baldwin DS, Hogue SL, Fehnel SE, Hollis KA, Edin HM (2006) Estimating the prevalence and impact of antidepressant-induced sexual dysfunction in 2 European countries: a cross-sectional patient survey. J Clin Psychiatry 67, 204–210.