Antidepressant-Induced Sexual Dysfunction: A comparison between Duloxetine and Escitalopram

Original Article Antidepressant-Induced Sexual Dysfunction: A comparison between Duloxetine and Escitalopram Anurag Jhanjee*, Pankaj Kumar*, Neeraj Kumar Gupta** *Department of Psychiatry, UCMS & GTB Hospital, Delhi, University of Delhi **Department of Psychiatry & Drug De-addiction Centre, Lady Hardinge Medical College, New Delhi-110001, India ABSTRACT Background: Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) have the potential to produce delayed ejaculation in men, delayed orgasm or anorgasmia in women and decreased libido that is independent of the gender. The occurrence of medication-associated sexual dysfunction increases the likelihood of medication non-compliance (or non-adherence) in patients, which may contribute to untreated depression and/or disease relapse. Materials & Methods: 60 patients with diagnosis of Depressive episode (in remission at the time of study), divided into 2 groups of 30 patients taking Duloxetine and the remaining 30 patients taking Escitalopram, were recruited on consecutive basis from the patients attending Psychiatry OPD of Lady Hardinge Medical College (LHMC). Each subject was rated on Arizona Sexual Experience Scale (ASEX) and the results obtained were statistically analyzed. Results: In the present study the average ASEX score obtained in the Escitalopram group (12.63) was found to be more than that in Duloxetine group (12.36), though this difference was not found to be statistically significant. Conclusions: These results illustrate that antidepressant-induced sexual dysfunction is reported frequently by patients taking SSRIs or SNRIs. Our study did not find any significant difference between escitalopram and duloxetine with respect to their sexual dysfunction profile but in view of the limitations of our study there is need for further research in this domain of psychopharmacology. Key words: Escitalopram, duloxetine, Arizona Sexual Experience Scale (ASEX) Sexual dysfunction has been reported to occur in approximately 30-70% of patients receiving antidepressant medications. Package insert data for selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants show rates of sexual dysfunction as a result of antidepressant use ranging from 0% to about 15% depending of the type of sexual dysfunction and the SSRI studied, with a mean rate of less than 10%. Antidepressant-induced sexual dysfunction is common but underreported. For instance, only 14.2% of depressed patients taking selective serotonin reuptake inhibitors (SSRIs) for depression spontaneously report sexual complaints; however, if queried directly, nearly 60% of patients report sexual complaints. 1 Using standardized instruments, such as the Arizona Sexual Experiences Scale (ASEX) 2 and the Changes in Sexual Functioning Questionnaire (CSFQ) 1, and asking phase-specific questions may facilitate the clinicians assessment of patients sexual dysfunction. There are a number of patient s risk factors for sexual dysfunction. These include age (being 50 years old or older), having less than a college level education, not being employed full-time, tobacco use (6-20 times per day), a prior history of 89

DELHI PSYCHIATRY JOURNAL Vol. 13 No.1 APRIL 2010 antidepressant-induced sexual dysfunction, a history of little or no sexual enjoyment, and considering sexual functioning as not or only somewhat important. 3 Gender, race, and duration of treatment, in contrast, do not appear to predict sexual dysfunction. Broadly speaking, there are 3 stages of sexual functioning [Stage 1: interest and desire (libido), Stage 2: physiologic arousal, and Stage 3: orgasm] and five primary neurotransmitters, dopamine (Stage 1), nitric oxide and acetylcholine (Stage 2), serotonin(stage 2 and 3), and norepinephrine (Stage 3), which are believed to play the most crucial roles in antidepressant-associated sexual dysfunction. 4 In general, the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs) seem to affect all stages of sexual functioning 5. For sexual dysfunction related to SSRI use, difficulties seem to occur most commonly in relation to Stages 2 and 3 due to their ability to enhance neurotransmission of serotonin. Although major depression has been associated with the occurrence of sexual dysfunction, many antidepressant agents can exacerbate or induce this problem. Therefore it is sometimes difficult to determine whether sexual difficulties in a medicated individual result from their psychiatric condition(s) or from the medications being used to treat them. Angst et al 6, examined 591 males and females in the age group of 20-35 years in the general population to determine the prevalence of sexual problems in depressed individuals. By comparing those subjects with depression to non-depressed subjects they found over a two-fold difference in the prevalence of sexual dysfunction (50% vs 24% respectively). The subjects with depression were subsequently stratified based on whether they were currently being treated for their depression. This analysis showed that 62% of those receiving pharmaco-therapy reported some sexual dysfunction, compared to 45% of those untreated, and 24% in the non-depressed controls. In one of the largest prospective studies of antidepressant-associated sexual dysfunction, by Montejo et al 7, it was found that 59.1 % of the patients experienced some form of sexual dysfunction after antidepr essant initiation. However, only 20.2% of patients reported their problem spontaneously and the remaining 79.8% would have gone undiscovered. Antidepressants with the highest r ates of dysfunction were citalopram (72.7%),paroxetine (70.7%), and venlafaxine (67.3%). Mirtazapine had a lower rate of dysfunction (24.4%) than the SSRIs as did nefazodone (8.0%), amineptine (6.9%), and moclobemide (3.9%). The most common adverse sexual effects of the SSRIs and venlafaxine were decreased libido and delayed orgasm. Paroxetine was associated with significantly higher rates of erectile dysfunction and decreased vaginal lubrication (p < 0.05) as compared to the other antidepressants. Males had a higher rate of dysfunction than females (62.4% vs. 56.9%), but females experienced more severe decreases in libido, delayed orgasm, and anorgasmia (p < 0.05). Twenty-seven percent of the patients showed good tolerance to the sexual side effects, 34.5% accepted it with some objection, and 38.3% considered it unacceptable and suggested that this significantly affected their desire to continue therapy with their current medication. Escitalopram is a selective serotonin reuptake inhibitor (SSRI) and Duloxetine is a Serotonin Norepinephrine Reuptake inhibitor (SNRI). Studies have demonstrated sexual dysfunction rates of 57 % to 73 % for SSRIs ( Montejo et al, 2001) 7 and 43 % for SNRIs ( Clayton AH, Pradko JF et al,2002 ). 3 Pooled data from 6 studies of duloxetine revealed that for patients without sexual dysfunction at baseline, the incidence of sexual dysfunction during the acute phase of treatment was significantly higher among patients receiving duloxetine than among those receiving placebo (46.4% vs. 28.8%) 8. In an 8-month, randomized double blind, placebocontrolled study of duloxetine and escitalopram, 114 of the 634 patients had no sexual dysfunction at baseline (based on the 14-itemChanges in Sexual Functioning Questionnaire). Of these, 33% of the patients receiving duloxetine, 43.6% of those receiving escitalopram and 25% of those receiving placebo reported sexual dysfunction at the end of 8 weeks of treatment. After 12 weeks, there were no statistically significant differences between drugs; however, Major Depressive Disorder (MDD) outcome (regardless of treatment) had a significant impact on improvement in global sexual functioning. 9 The occurrence of medication-associated 90

sexual dysfunction increases the likelihood of medication non-compliance (or non adherence) in the patients, which may contribute to untreated depression and/or disease relapse. The present study aims to find out and compare the sexual dysfunction profile in patients taking escitalopram and duloxetine as this information is clinically relevant in determining the probability of patient s noncompliance and in selecting the most suitable antidepressant for the patient Materials and methods Sixty subjects with diagnosis of Depressive episode (ICD-10 DCR), and who were in remission at the time of the study (Hamilton Depression Rating Scale (17 item ) {HDRS total score < 7} were selected from the patients attending the outpatient services of department of Psychiatry, Lady Hardinge Medical College and Associated Smt. Sucheta Kriplani Hospital on consecutive basis such that there were two groups - the first group comprising of 30 patients taking Escitalopram and the second group comprising of 30 patients taking Duloxetine. Subjects that were excluded from the study included those suffering from any medical or surgical conditions, those with a history of co morbid substance abuse, pregnant and lactating women, and those suffering from any psychiatric disorder other than depression in order to ensure that results of our study were not influenced by these confounding factors. Arizona Sexual Experience Scale (ASEX) 2 was administered on subjects in both the groups after obtaining informed consent. ASEX is a user friendly five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/ penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with higher scores indicating more sexual dysfunction. ASEX has shown an excellent internal consistency and reliability, and strong test retest reliability in patients with depression (McGahuey et al., 2000) 2. Although its sensitivity to change has not been formally tested, data from its extensive use in interventional studies suggest that the ASEX can also effectively measure changes in sexual function over time (McGahuey et al., 2000) 2. The results of the study were statistically analyzed using Microsoft Excel. Results There were a total of 16 female and 14 male subjects in the Escitalopram group, while in the duloxetine group; there were 21 female and 9 male subjects. The age distribution in the two groups is tabulated below: Age distribution 18 16 14 12 10 8 6 4 2 0 Number of subjects Age group Escitalopram Duloxetine (in years) group group 18-27 2 5 28-37 16 10 38-47 8 11 48-57 4 4 Age distribution 18-27 28-37 38-47 48-57 Age Range Series1 Series2 The mean age of escitalopram group was 36.63 (S.D- 7.60) and that of the duloxetine group was 36.6 (S.D- 9.75), on analysis there was no statistical difference between the mean ages of the two groups. Comparison of age distribution: Group Mean ± S.D. p value Escitalopram Group 36.63 ± 7.60 Duloxetine Group 36.6 ± 9.75 0.988 The two groups were compared with respect to average total score on HDRS (17 item) and as shown below the difference between the two groups was not found to be statistically significant. Number of subjects 25 20 15 10 5 0 Sex distribution 1 2 Escita lopra m Dul ox e tine Male Fem ale 91

DELHI PSYCHIATRY JOURNAL Vol. 13 No.1 APRIL 2010 Comparison of average HDRS score Group Mean ± S.D. p value Escitalopram Group 5.56 ± 0.504 0.434 Duloxetine Group 5.66 ± 0.479 In the present study the average ASEX score obtained in the Escitalopram group (12.63) was found to be more than that in Duloxetine group (12.36), but it was not found to be statistically significant. HDRS average score 5.68 5.66 5.64 5.62 5.6 5.58 5.56 5.54 Av HDRS Comparison of average ASEX scores: Variable Mean ± S.D P Value Net a Sex Score Escitalopram Group 12.63 ± 3.134 0.697 Duloxetine Group 12.36 ± 2.042 A Sex Item 1 Escitalopram Group 2.6 ± 0.770 0.377 Duloxetine Group 2.43 ± 0.678 A Sex Item 2 Escitalopram Group 2.33 ± 0.802 0.537 Duloxetine Group 2.46 ± 0.860 A Sex Item 3 Escitalopram Group 2.36 ± 0.964 0.661 Duloxetine Group 2.26 ± 0.784 A Sex Item 4 Escitalopram Group 2.53 ± 0.899 0.608 Duloxetine Group 2.43 ± 0.568 A Sex Item 5 Escitalopram Group 2.83 ± 0.746 0.718 Duloxetine Group 2.76 ± 0.678 5.52 5.5 Escitalo Duloxetine Scores on individual items between the two groups was compared and here also no statistically significant difference was found. In both the groups maximum individual scores was obtained on the item Are your orgasms satisfying? Clinical sexual dysfunction (ASEX total score>18) was found in 3 subjects (1 male and 2 females) out of 60 subjects; Two out of three subjects belonging to the Escitalopram group. ASEX average score 92 12.65 12.6 12.55 12.5 12.45 12.4 12.35 12.3 12.25 12.2 Escitalo Av ASEX Duloxetine Discussion In the present study only 5 % of the subjects showed clinical sexual dysfunction which is less than the reported incidence of sexual dysfunction associated with antidepressant therapy of 22% to 43% (Clayton AH et.al, 2002) 3.As regards the sexual drive, 10% subjects in the Escitalopram group reported somewhat weak as compared 3.3% subjects in duloxetine group. In the Escitalopram group, 20% reported some dissatisfaction in orgasms as compared to 13.3% in the Duloxetine group. These results are consistent with studies showing greater sexual dysfunction with escitalopram than Duloxetine (Kornstein S, Mallinckrodt C et.al, 2007) 9. As regards the total ASEX score, there was no statistically significant difference between the two groups. The results of our study show that antidepressant-induced sexual dysfunction is a common problem in the depressed patients, though scarcely repor ted. Using standardized instruments, such as the Arizona Sexual Experiences Scale (ASEX) 2 and the Changes in Sexual Functioning Questionnaire (CSFQ) 1, and asking phase-specific questions may facilitate the clinicians assessment of patients sexual dysfunction. Though our study did show that sexual dysfunction is reported by the patients taking

escitalopram and duloxetine, it did not find any statistically significant difference between these two groups. In view of the limitations of our study (as detailed below), there is an overbearing need for a well designed prospective study to find out if escitalopram and duloxetine differ significantly with respect to their sexual adverse effect profile. The answer to the above question is surely going to be one of the many considerations that will influence the choice of the most appropriate antidepressant for our patients. Limitations of the present study Sample size of 30 appears inadequate for a comprehensive insight into the domain of antidepressant-induced sexual dysfunction and as such a larger sample will prove to be more useful. Our study was cross-sectional in design, a better approach to decipher the adverse impact of antidepressants on patient s sexual functioning would include a careful follow up of the patient at regular intervals as this will help in finding out how the sexual adverse effects, as reported by patient, fare over a period of time. Conclusions Our study has shown that patients of depression (in remission at the time of study) taking either escitalopram (an SSRI) or duloxetine (an SNRI) reported sexual dysfunction as exhibited by high scores on ASEX. Though our study did not find statistically significant difference between sexual dysfunction profile of escitalopram and duloxetine, it is sincerely hoped that it will stimulate researchers to carry out studies in this domain of psychopharmacology. Further research is needed in the area of sexual dysfunctions associated with use of SSRIs and SNRIs as it may guide the selection of a suitable drug such that chances of treatment noncompliance and discontinuation are minimized and better treatment outcomes can be ensured. References 1. Clayton AH, McGarvey EL, Clavet GJ. The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity. Psychopharmacol Bull 1997a; 33 : 731 745. 2. McGahuey CA, Gelenberg AJ, Laukes CA, Moreno FA, Delgado PL, McKnight KM, Manber R. The Arizona Sexual Experience Scale (ASEX): reliability and validity. J Sex Marital Therap 2000; 26 : 25 40. 3. Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63 : 357-366. 4. Rosen RC, Lane RM, Menza M. Effects of SSRIs on sexual function: a critical review. J Clin Psychopharmacol 1999; 19(1) : 67-8. 5. Zajecka J. Strategies for the treatment of antidepressant-related sexual dysfunction. J Clin Psychiatry 2001; 62 Suppl 3 : 35-43. 6. Angst J. Sexual problems in healthy and depressed persons. Int Clin Psychopharmacol 1998; 13 Suppl 6 : S1-4. 7. 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. 8. Hudson JI, Wohlreich MM, Kajdaz DK, et al. Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials. Hum Psychopharmacol Clin Exp 2005; 20 : 327-41. 9. Clayton A, Kornstein S, Prakash A, Mallinckrodt C, Wohlreich M. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sex Med 2007; 4 : 917 929. 93