|Ahead of print publication
Antidepressant-induced sexual dysfunction: A naturalistic study comparing sexual dysfunction among patients taking escitalopram, desvenlafaxine, and mirtazapine
Raj Kiran Donthu1, J Shivanand Manohar2, Ravish Thunga3
1 Department of Psychiatry, Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, Andhra Pradesh, India
2 Department of Psychiatry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
3 Department of Psychiatry, AJ Institute of Medical Sciences, Mangalore, Karnataka, India
|Date of Submission||25-Oct-2020|
|Date of Decision||28-Dec-2020|
|Date of Acceptance||28-Dec-2020|
|Date of Web Publication||02-Apr-2021|
J Shivanand Manohar,
Department of Psychiatry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore - 570 015, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Antidepressant drugs are frequently associated with sexual dysfunction. Sexual side effects affect the patients' quality of life and in the long term and can lead to noncompliance and relapse. However, studies covering many antidepressants with different mechanisms of action are scarce. Aims: The aim of this study is to compare the rates of sexual dysfunction among patients taking escitalopram, desvenlafaxine, and mirtazapine. Settings and Design: Cross-sectional study. Materials and Methods: Arizona Sexual Experience Scale (ASEX), Hamilton Rating Scale for Depression (21 items), and State and Trait Anxiety Inventory. Statistical Analysis Used: Fisher's exact t-test, Chi-square test, and analysis of variance depending on the type of variable. Results: Eighty-four participants (42 males and 42 females) completed all instruments. Of these, 28 were taking escitalopram (13.93 ± 5.15), 28 were taking desvenlafaxine (76.79 ± 25.39), and 28 were taking mirtazapine (16.88 ± 3.88). A substantial number of patients (40.5%, n = 34) had sexual dysfunction. The prevalence of sexual dysfunction varied across the drugs; escitalopram (60.7%), desvenlafaxine (35.7%), and mirtazapine (25%). Regression analysis revealed that the significant factor for sexual dysfunction was the type of antidepressant used. The mirtazapine group's total ASEX score was significantly lower than the scores for escitalopram and desvenlafaxine (χ2 = 7.807, P = 0.020). Conclusion: The incidence of sexual dysfunction is substantially high during antidepressant treatment. The rates of sexual dysfunction differed among antidepressants having different mechanisms of action. Mirtazapine-induced lesser sexual dysfunction compared to desvenlafaxine and escitalopram.
Keywords: Antidepressive agents, sexual dysfunction, side effects of drugs
|How to cite this URL:|
Donthu RK, Manohar J S, Thunga R. Antidepressant-induced sexual dysfunction: A naturalistic study comparing sexual dysfunction among patients taking escitalopram, desvenlafaxine, and mirtazapine. Ann Indian Psychiatry [Epub ahead of print] [cited 2021 Apr 20]. Available from: https://www.anip.co.in/preprintarticle.asp?id=312912
| Introduction|| |
The treatment of depression has been advanced in recent years by the introduction of several new antidepressants. Among these are selective serotonin reuptake inhibitors, (SSRIs, e.g.,: escitalopram and sertraline), serotonin norepinephrine reuptake inhibitors, (SNRIs, e.g.,: Venlafaxine desvenlafaxine), noradrenergic-specific serotonergic antidepressants (NASSA, e.g.,: mirtazapine). These newer medications have comparable efficacy to tricyclic antidepressants and monoamine oxidase inhibitors but offer significant improvements in ease of dosing, overall side effect profiles, and reduced risk of toxicity. Current treatment guidelines indicate that the effectiveness of antidepressant medications is generally comparable. Therefore, one of the primary factors that should be considered in selecting an antidepressant is the constellation of anticipated side effects of the drug.,,,,
Although the spontaneous reports of sexual dysfunction listed in product labeling for these newer antidepressants indicate a relatively low incidence of sexual side effects (i.e., <15%), sexual dysfunction has been reported in up to 70% of patients when direct enquiry regarding sexual functioning occurs. Specifically, several studies have demonstrated that newer antidepressants are associated with higher sexual dysfunction than their product labeling indicates.,,, However, because of the differing methodologies used to collect sexual functioning data, it is often difficult to compare the rates of sexual dysfunction across studies. The rates of sexual dysfunction reported with SSRI range from 34% to 70% of patients across studies in which patients were directly questioned about their sexual functioning.,,,,,, During antidepressant treatment, typical sexual dysfunction symptoms include diminished or absent libido, arousal difficulties, erectile dysfunction (in male) vaginal lubrication difficulties (in females), delayed orgasm, and anorgasmia.,
The importance of recognizing sexual dysfunction is two-fold. First, sexual dysfunction is a common cause of noncompliance with antidepressant treatment regimens, which can lead to relapse of depression.,, Second, the impact of unrecognized antidepressant-induced sexual dysfunction not only affects the patients quality of life (e. g: interpersonal relationship and self-esteem), but may actually interfere with recovery from a depressive episode.
Lack of recognition of sexual dysfunction occurs commonly in the clinical settings. Despite the importance of sexual functioning in patients' lives, many physicians are reluctant to specifically address sexual functioning in patients. Physician assessment of sexual dysfunction is hampered by a number of factors: inadequate training for obtaining sexual history, social barriers, lack of knowledge about sexual functioning, lack of knowledge about how to treat sexual dysfunction, and fear of the line of questioning being misinterpreted as inappropriate. However, more than 90% of patients believe that having physician collect information on sexual history has considerable benefit.
| Materials and Methods|| |
Ethical committee approval for the study was taken from the Institutional Ethical Committee. We recruited participants from the outpatient department of psychiatry of a tertiary care teaching hospital. Patients were eligible if they were in the age group of 18 and 50 years had been taking one of the antidepressant; escitalopram, desvenlafaxine, or mirtazapine as monotherapy or with benzodiazepines, for at least 6 weeks, patients who were sexually active (defined as having experienced sexual intercourse, masturbation, sexual fantasy, or others sexual activity), were willing to discuss their sexual functioning with the physician and give informed consent. Patients were excluded for any of the following reasons – patients who were diagnosed with sexual dysfunction or had any complaints regarding sexual functioning before the onset of treatment with the above said drugs, had uncontrolled psychiatric disorders which have severe psychomotor retardation or psychotic symptoms, had medical conditions such as diabetes mellitus, history of stroke, congestive heart failure, unstable cardiac conditions, arrhythmias or myocardial infarction, trauma to genitals, and had gender orientation-related disorders.
As mentioned, participants' sexual functioning was assessed using Arizona Sexual Experience Scale (ASEX). The scale has demonstrated good internal consistency, having a test retest reliability of significance at 0.01 level. The ASEX's sensitivity and specificity for identifying sexual dysfunction in participants are 82% and 90%, respectively. In ASEX, participants rate their current level of sexual drive, psychological arousal, physiological arousal, ease of orgasm, and orgasm satisfaction on a 6-point Likert scale. Ratings range from 1 – extremely positive to 6 – none or never, for each of the five items, for a total score ranging from 5 to 50. A total ASEX score of 19 or greater or any one item with an individual score of 5 or greater or any three items with individual scores of 4 or greater are all highly correlated with the presence of clinically diagnosed sexual dysfunction. To control for the effect of depression and anxiety on sexual functioning, we also assessed the participants using Hamilton Rating Scale for Depression (HAMD) and State Trait Anxiety Inventory (STAI).,
The study data were analyzed using the Statistical Package for Social Sciences (SPSS) version 18 (IBM Corp, SPSS Inc.., Chicago); tests used were Fisher exact t-test, Chi-square test, and analysis of variance depending on the type of variable. Among the participants using different antidepressants, we compared the ASEX scale scores and the subscales using Bonferroni's multiple comparison test. We used multiple regression analysis to determine which the variables related to sexual dysfunction, considering a probability (P) value of < 0.05 to be significant.
| Results|| |
Eighty-four participants (42 males and 42 females) completed all instruments. Of these 28 were taking escitalopram (13.93 ± 5.15), 28 were taking desvenlafaxine (76.79 ± 25.39), and 28 were taking mirtazapine (16.88 ± 3.88).
Mean ages, sex ratio, education, martial status, and socioeconomic status did not differ significantly across these antidepressants [Table 1]. There was no statistically significant difference in the prevalence of sexual dysfunction in relation to the participants' gender or socio-demographic background. The dosage of the drugs and the HAMD and STAI scores did not have a statistically significant difference either [Table 2].
|Table 1: Demographic details pertaining to participants taking various antidepressants|
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|Table 2: Comparison of dosage, Hamilton Rating Scale for Depression, State, and Trait Anxiety Inventory scores among different antidepressants|
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A substantial number of patients (40.5%, n = 34) had sexual dysfunction after the initiation of treatment. Regression analysis revealed that the significant factor for sexual dysfunction was the type of antidepressant used. The prevalence of sexual dysfunction varied across the drugs: escitalopram (60.7%), desvenlafaxine (35.7%), and mirtazapine (25%) [Figure 1]. The mirtazapine group's total ASEX score was significantly lower than the scores of escitalopram and desvenlafaxine (χ2 = 7.807, P = 0.020) [Table 3]. In the ASEXs subscore for sexual drive, there was a statistically significant difference found for the participants treated with mirtazapine, with the subscore being markedly lower than that for escitalopam and desvenlafaxine [Table 4] and [Table 5].
|Table 4: Comparison of Arizona Sexual Experience Scale total and subscale scores|
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| Discussion|| |
Sexual dysfunction associated with antidepressant treatment is not uncommon. Although in many cases, antidepressants can improve the sexual dysfunction associated with depression, the dysfunction consequent to medication themselves is potentially important consensus for the patients.,, Double-blind placebo-controlled trails that assessed SSRI associated sexual dysfunction by direct questioning found a significantly higher dysfunction than the placebo.,,,,, A meta-analysis done by Serrati et al. found that sexual dysfunction in patients receiving antidepressants ranged from 25.8% to 80.3% of patients. The antidepressants implicated in causation of sexual dysfunction in the decreasing order of impact were as follows: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenlezine, duloxetine, escitalopram, and fluvoxamine. Drugs such as bupropion, mirtazapine, and nefazadone were less associated with sexual dysfunction.
The mechanism by which the SSRIs induce sexual dysfunction is probably multifactorial but appears to be primarily related to their effect on serotonin through stimulation of 5HT2C receptors apart from others such as cholinergic receptor blockade and nitric oxide synthase inhibiting effect.
There is some evidence to suggest that SNRIs through their noradrenergic effect may mitigate the serotonin influence on sexual function, although the results of studies on evaluating SNRIs have been inconsistent. Desvenlafaxine succinate which is a major metabolite of desvenlafaxine seems to have lower sexual adverse effects in women compared with men, although these studies have relied on spontaneous self-report only. However, systematic studies on sexual dysfunction caused by desvenlafaxine are lacking., In a randomized, double-blind trial, no statistically significant differences were found between desvenlafaxine (50–100 mg) and placebo in causation of sexual dysfunction. The results of another recent naturalistic and prospective study show that sexual functioning improved in both patient groups that they studied – the desvelafaxine-naïve patients as well as those switched to desvenlafaxine from another antidepressant, as measured by the overall score of the SALSEX scale.
Mirtazapine stimulates noradrenergic and serotonergic activity by its agonist effects on postsynaptic 5-HT1A receptors and concurrent antagonist effects on 5-HT2 and 5-HT3 receptors. The 5-HT2 blockade mechanism is thought to prevent serotonin-mediated adverse effects on sexual function. On the basis of this, it is claimed that in comparison to SSRIs and venlafaxine, mirtazapine is significantly less likely to produce sexual dysfunction., In fact, a systematic assessment of sexual function among depressed outpatients found that mirtazapine may enhance sexual functioning in both men and women. Ozmenler et al. also report that when remitted patients with SSRI-induced sexual dysfunction were switched to mirtazapine, approximately half of them reported no sexual dysfunction at the end of the 8-week treatment. There is also preliminary evidence to suggest the mirtazapine improves duloxetine-induced sexual dysfunction.
However, studies which compared the rates of sexual dysfunction with mirtazapine versus serotonergic antidepressants have come up with inconsistent results, with some studies,,, showing higher rates of sexual dysfunction during SSRI treatment and other studies,, showing no difference between the two treatment groups. A recent study with a naturalistic design in patients with depression or anxiety disorder treated with various antidepressants, assessed the sexual function using the PRSexDQ-SALSEX questionnaire at baseline and at 6 weeks. Twenty-one percentage of participants showed sexual dysfunction at the beginning of the treatment which increased to 41% in week 6. With regard to individual questionnaire items, by week 6, sexual desire improved, but erectile and ejaculatory function in men and orgasmic function in women worsened. Mirtazapine was associated with favorable sexual function. At week 2, mirtazapine and desvenlafaxine were the predictors of favorable sexual outcome. Some studies report that while mirtazapine leads to sexual dysfunction, the intensity is significantly lower. The present study showing mirtazapine being associated with both lowest overall sexual dysfunction frequency and greatest ease of orgasm is in line with mirtazapine's unique mechanism of action.
Vortioxetine, a relatively new antidepressant with a multimodal mechanism of action at serotonergic, noradrenergic, and dopaminergic receptors, seems to be associated with lower sexual dysfunction, according to the data from clinical trials, as well as a specific study However, additional data from clinical practice settings are needed to corroborate these findings.
This study has several limitations since response rate is generally low in surveys on sensitive topics, and interpretation of the findings requires caution. One limitation is that we did not make an initial assessment of participants' sexual dysfunction in the past, before present episode and treatment. It is also difficult to distinguish antidepressant-induced sexual dysfunction from dysfunction that may be a residual symptom of depression. However, since the participants' severity of depression was mild, their sexual dysfunction may be more likely be the result of medication side effects. Patients were also allowed to continue taking benzodiazepines, if prescribed, since ours was a naturalistic study. Benzodiazepines could have an adverse effect on sexual functioning., However, it is unlikely that benzodiazepines were the cause for the sexual dysfunction during the course of this study, owing to the short duration (6 weeks) and low doses used.
| Conclusion|| |
The current study suggests that 25%–60% of participants receiving either desvenlafaxine, mirtazapine, or escitalopram develop sexual dysfunction. The prevalence of antidepressant-induced sexual dysfunction depends on the type of antidepressant used, with participants on mirtazapine developing the least amount of sexual dysfunction, among the three drugs. Clinician should be alert of this undesirable side effect to adopt the strategy in managing the depression, thus avoiding deterioration in the patients' quality of life and possible withdrawal from the treatment.
Declaration of patient consent
Patient consent statement was obtained from each patient as per the Institutional Ethics Committee approval along with consent taken for participation in the study and publication of the scientific results/clinical information/image without revealing their identity, name or initials. The patient is aware that though confidentiality would be maintained anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Clayton AH, Pradho JF. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002;63:357-66.
Stahl SM. Antidepressant “Sthals Essentials of Psycholpharmacology.” 3rd
ed. United Kingdom:Cambridge Publication; 2008:566.
Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry 2000;157:1-45.
Crismon ML, Trivedi M, Pigott TA, Rush AJ, Hirschfeld RM, Kahn DA, et al
. The texas medication algorithm project: Report of the texas consensus conference panel on medication treatment of major depressive disorder. J Clin Psychiatry 1999;60:142-56.
Roose SP. Tolerability and patient compliance. J Clin Psychiatry 1999;60 Suppl 17:14-7.
Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 2000;61:276-81.
Croft H, Settle E Jr., Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther 1999;21:643-58.
Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, Houser TL, et al
. Sexual dysfunction associated with the treatment of depression: A placebo-controlled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry 1999;11:205-15.
Kavoussi RJ, Segraves RT, Hughes AR, Ascher JA, Johnston JA. Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients. J Clin Psychiatry 1997;58:532-7.
Feiger A, Kiev A, Shrivastava RK, Wisselink PG, Wilcox CS. Nefazodone versus sertraline in outpatients with major depression: Focus on efficacy, tolerability, and effects on sexual function and satisfaction. J Clin Psychiatry 1996;57 Suppl 2:53-62.
Balon R, Yeragani VK, Pohl R, Ramesh C. Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 1993;54:209-12.
Jacobsen FM. Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 1992;53:119-22.
Montejo-Gonzalez AL, Llorca G, Izqueirodo JA, Ledesma A, Bousoño M, Calcedo A, et al.
SSRI- induced sexual dysfunction. Fluoxetine, paroxetine, sertraline and fluvoxamine in a prospective, multicenter and descriptive clinical study of 344 patients. J Sex Marital Ther 1997;23:176-94.
Lee KU, Lee YM, Nam JM, Lee HK, Kweon YS, Lee CT, et al
. Antidepressant-induced sexual dysfunction among newer antidepressants in a naturalistic setting. Psychiatry Investig 2010;7:55-9.
Rochschild AJ. Sexual side effects of antidepressants. J Clin Psychiatry 2000;61 Suppl 11:28-36.
Zajecka JM. Clinical issues in long-term treatment with antidepressants. J Clin Psychiatry 2000;61 Suppl 2:20-5.
Piazza LA, Clayton Ah and Ware MR. Sexual dysfunction and antidepressant therapy. Miami, Fla: Presented at the 148th
Annual Meeting of the American Psychiatric Association; 1995. p. 20-5.
McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, et al
. The Arizona sexual experience scale (ASEX): Reliability and validity. J Sex Marital Ther 2000;26:25-40.
Zheng YP, Zhao JP, Phillips M, Liu JB, Cai MF, Sun SQ, et al
. Validity of the Hamilton rating scale for depression. Br J Psychiatry 1998;152:49-52.
Spiellberger CD. Manual for the State Trait Anxiety Inventory: A Comprehensive Bibliography. Palo Alto, CA: Consulting Psychologists Press; 1989.
Spielberger CD. Manual for the State Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press; 1983.
Avasthi A, Rao TS, Sandeep G, Parthasarathy B, Suresh K. Clinical practice guidelines for management of sexual dysfunction. Indian J Psychiatry 2017;59:S91-115.
Montejo AL, Llorca G, Izquierdo JA, Rice-Villademoros F. The Spanish working group for the study of psychotrpic related sexual dysfunction. J Clin Psychiatry 2001;62 Suppl 3:10-21.
Margolese HC, Assalian P. Sexual side effects of antidepressants: A review. J Sex Marital Ther 1996;22:209-17.
Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil TM, LaPierre YD, et al
. Antidepressant efficacy of sertraline: A double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry 1990;51 Suppl B: 18-27.
Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry 1998;10:145-50.
Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, Richard N, et al
. A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Clin Ther 2001;23:1040-58.
Clayton AH, Croft HA, Horrigan JP, Wightman DS, Krishen A, Richard NE, et al
. Bupropion extended release compared with escitalopram: Effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry 2006;67:736-46.
Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: A meta-analysis. J Clin Psychopharmacol 2009;29:259-66.
Pollack MH, Reiter S, Hammerness P. Genitourinary and sexual adverse effects of psychotropic medication. Int J Psychiatry Med 1992;22:305-27.
Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, Wang F, et al
. Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry 2005;66:686-92.
Liebowitz MR, Manley AL, Padmanabhan SK, Ganguly R, Tummala R, Tourian KA. Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder. Curr Med Res Opin 2008;24:1877-90.
Septien-Velez L, Pitrosky B, Padmanabhan SK, Germain JM, Tourian KA. A randomized, double-blind, placebo-cotrolled trail of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol 2007;22:338-47.
Clayton AH, Tourian KA, Focht K, Hwang E, Cheng RF, Thase ME. Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major depressive disorder: A phase 4, randomized controlled trial. J Clin Psychiatry 2015;76:562-9.
Montejo AL, Becker J, Bueno G, Fernández-Ovejero R, Gallego MT, González N, et al
. Frequency of Sexual dysfunction in patients treated with desvenlafaxine: A Prospective naturalistic study. J Clin Med 2019;8:719.
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 3:10-21.
Werneke U, Northey S, Bhugra D. Antidepressants and sexual dysfunction. Acta Psychiatr Scand 2006;114:384-97.
Boyarsky BK, Haque W, Rouleau MR. Sexual dysfunctioning in depressed outpatients taking mirtazapine. Depress Anxiety 1999;9:175-9.
Ozmenler NK, Karlidere T, Bozkurt A, Yetkin S, Doruk A, Sutcigil L, et al
. Mirtazapine augmentation in depressed patients with sexual dysfunction due to SSRIs. Hum Psychopharmacol 2008;23:321-6.
Ravindran LN, Eisfeld BS, Kannedy SH. Combining mirtazapine and duloxetine in treatment resistant depression improves outcome and sexual dysfunction. J Clin Psychopharmacol 2008;28:107-8.
Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry 2000;61:656-63.
Philipp M, Tiller JW, Baier D, Kohnen R. Comparison of moclobemide with selective serotonin reuptake inhibitors (SSRIs) on sexual function in depressed adults. The Australian and German Study Groups. Eur Neuropsychopharmacol 2000;10:305-14.
Montgomery SA. Safety of mirtazapine: A review. Int Clin Psychopharmacol 1995;10 Suppl 4:37-45.
Saiz-Ruiz J, Montes JM, Ibáñez A, Díaz M, Vicente F, Pelegrín C, et al
. Assessment of sexual functioning in depressed patients treated with mirtazapine: A naturalistic 6-month study. Hum Psychopharmacol 2005;20:435-40.
Bahnke K, Sogaard J, Martin S, Bauml J, Ravindran AV, Agren H, et al
. Mirtazapine orally disintegrating tablet versus sertraline: A propective onset of action study. J Clin Psychopharmacol 2003;23:358-64.
Wade A, Crawford GM, Angus M, Wilson R, Hamilton L. A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Int Clin Psychopharmacol 2003;18:133-41.
Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schuttle AJ. Comparison of the effects of mirtazapine and fluoxetine in severly depressed patients. CNS Drugs 2005;19:137-46.
Preeti S, Jayaram SD, Chittaranjan A. Sexual dysfunction in patients with antidepressant-treated anxiety or depressive disorders: A pragmatic multivariable longitudinal study. East Asian Arch Psychiatry 2018;28:9-16.
Mahableshwarkar AR, Jacobsen PL, Serenko M, Chen Y, Trivedi MH. 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;76:583-91.
Alam MY, Jacobsen PL, Chen Y, Serenko M, Mahableshwarkar AR. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: Results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol 2014;29:36-44.
Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of vortioxetine vs. escitalopram on sexual functioning in adults with well-treated major depressive disorder experiencing SSRI-induced sexual dysfunction. J Sex Med 2015;12:2036-48.
Asch DA, Jedrziewski MK, Christakis NA. Response rates to mail surveys published in medical journals. J Clin Epidemiol 1997;50:1129-36.
Dunn KM, Croft PR, Hackett GI. Sexual problems: A study of the prevalence and need for health care in the general population. Fam Pract 1998;15:519-24.
Kupelian V, Hall SA, McKinlay JB. Common prescription medication use and erectile dysfunction: Results from the Boston area community health (BACH) survey. BJU Int 2013;112:1178-87.
Mazzilli R, Angeletti G, Olana S, Delfino M, Zamponi V, Rapinesi C, et al
. Erectile dysfunction in patients taking psychotropic drugs and treated with phosphodiesterase-5 inhibitors. Arch Ital Urol Androl 2018;90:44-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]