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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 30-35

Antidepressant-induced sexual dysfunction: A naturalistic study comparing sexual dysfunction among patients taking escitalopram, desvenlafaxine, and mirtazapine


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 Submission25-Oct-2020
Date of Decision28-Dec-2020
Date of Acceptance28-Dec-2020
Date of Web Publication02-Apr-2021

Correspondence Address:
Dr. J Shivanand Manohar
Department of Psychiatry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore - 570 015, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_125_20

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  Abstract 


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 article:
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 2021;5:30-5

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 [serial online] 2021 [cited 2021 Jul 25];5:30-5. Available from: https://www.anip.co.in/text.asp?2021/5/1/37/312912




  Introduction Top


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.[1],[2],[3],[4],[5]

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.[6] Specifically, several studies have demonstrated that newer antidepressants are associated with higher sexual dysfunction than their product labeling indicates.[7],[8],[9],[10] 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.[7],[8],[9],[10],[11],[12],[13] 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.[5],[14]

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.[5],[15],[16] 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.[17]


  Materials and Methods Top


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).[18] 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)[19] and State Trait Anxiety Inventory (STAI).[20],[21]

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 Top


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 3: Comparing the Arizona sexual experience (ASEX) scale scores

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Table 4: Comparison of Arizona Sexual Experience Scale total and subscale scores

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Table 5: Comparison among the different groups

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Figure 1: Frequency of sexual dysfunction among various antidepressants

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  Discussion Top


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.[22],[23],[24] Double-blind placebo-controlled trails that assessed SSRI associated sexual dysfunction by direct questioning found a significantly higher dysfunction than the placebo.[7],[8],[25],[26],[27],[28] 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.[29]

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.[30]

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.[31] 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.[32],[33] In a randomized, double-blind trial, no statistically significant differences were found between desvenlafaxine (50–100 mg) and placebo in causation of sexual dysfunction.[34] 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.[35]

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.[36],[37] In fact, a systematic assessment of sexual function among depressed outpatients found that mirtazapine may enhance sexual functioning in both men and women.[38] Ozmenler et al.[39] 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.[40]

However, studies which compared the rates of sexual dysfunction with mirtazapine versus serotonergic antidepressants have come up with inconsistent results, with some studies[41],[42],[43],[44] showing higher rates of sexual dysfunction during SSRI treatment and other studies[45],[46],[47] 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.[48] Some studies report that while mirtazapine leads to sexual dysfunction, the intensity is significantly lower.[37] 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[49],[50] as well as a specific study[51] 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[52],[53] 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.[54],[55] 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 Top


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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

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