Abstract
Objectives
The current study compares the risk of sexual pain in depressed female patients in remission between those who were treated with Escitalopram and Fluoxetine. The associated factors were also examined.
Methods
This is a cross-sectional study involved 112 depressed female patients (56 treated with Escitalopram and 56 treated with Fluoxetine) who were in remission (as defined by Diagnostic and Statistical Manual-IV (DSM-IV) in the past 2 months and Montgomery-Asberg Depression Rating Scale (MADRS) score of ≤ 10) from the psychiatric clinic, University Kebangsaan Malaysia Medical Centre (UKMMC). They were interviewed using Structured Clinical Interview for DSM-IV (SCID). Hypoactive sexual desire was assessed using the Pain subscale of Malay Version of the Female Sexual Function Index (MVFSFI).
Results
The results show that risk of sexual pain was relatively low (16.07% for all patients), with no statistical significant between the two groups (17.86% for fluoxetine group, 14.29% for escitalopram group). Older age (adjusted odds ratio = 1.524, 95% CI = 1.199, 1.938) was the only factor significantly associated with sexual pain disorder.
Conclusions
There should not be any barrier when continuing the use of escitalopram or fluoxetine as antidepressants amongst the female patients.
Keywords: sexual pain, fluoxetine, escitalopram, depression, female
Introduction
Female sexual dysfunction (FSD) is a heterogeneous, multisystemic and multidimensional medical problem that comprises both biological and psychosocial components. In America, the prevalence of this condition among the women is 30–50%, and it is found to be age-related and progressive.1 The Sexual Function Health Council of the American Foundation which convened the American Foundation of Urologic Disease (AFUD) Consensus Panel, has further classified the FSD into Hypoactive Sexual Desire Disorder, Sexual Aversion Disorder, Sexual Arousal Disorder, Orgasmic Disorder and Sexual Pain Disorders.2
Sexual pain disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) as either dyspareunia or vaginismus. Dyspareunia is defined by the DSM–IV–TR as ‘‘(A) Recurrent or persistent genital pain associated with sexual intercourse in either a male or a female; (B) The disturbance causes marked distress or interpersonal difficulty; (C) The disturbance is not caused exclusively by vaginismus or lack of lubrication, is not better accounted for by another Axis I disorder (except another Sexual Dysfunction), and is not due exclusively to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition’’. Vaginismus is defined by the DSM–IV–TR as ‘‘(A) Recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse; (B) The disturbance causes marked distress or interpersonal difficulty; (C) The disturbance is not better accounted for by another Axis I disorder (e.g., Somatization Disorder) and is not due exclusively to the direct physiological effects of a general medical condition’’.3
Sexual pain disorder, which is the most frustrating sexual dysfunction, has the most negative psychological impact on the relationships, such as having fear for sexual activity and avoidance of sexual activity.4 Reduction in sexual satisfaction can therefore leads to an overall reduction of well-being and general happiness in women.5 Josie Butcher has further classified sexual pain into primary, when the pain occurs during sexual activity; or secondary, when it occurs after a period of pain free intercourse.4
From the medication point of view, we look at the selective serotonin reuptake inhibitor (SSRI) because it is the first line treatment for many psychiatric disorders such as major depressive disorder, anxiety disorder, personality disorder and others. SSRI is considered safe and cost effective but with troublesome side effects, one of them being sexual dysfunction. It is not understood why SSRI produce sexual side-effects, but some studies suggests that activation of the 5-hydroxytryptamine (5-HT2) receptor impairs sexual functioning, and stimulation of the 5-HT1A receptor facilitates sexual functioning.6 Many studies and theories have tried to explore the roles of neurotransmitters and hormones in maintaining normal sexual function, however the precise actions and aetiologies are never fully understood. In 2005, Berman classified the aetiologies of sexual pain disorders into vasculogenic, neurogenic, hormonal, musculogenic and psychogenic components. But often, the aetiologies may be multifactorial and at times overlapping.1
In Malaysia, the whole area of sexual dysfunction is still largely unexplored and to date there are not many studies on sexual dysfunction associated with antidepressants. Sidi et al. in one recent study looked at the prevalence of FSD components (desire, arousal, lubrication, orgasm and satisfaction) in an overall manner, among Malaysian women receiving antidepressants.7 However, there is no local study focusing on the prevalence of sexual pain in Malaysian female in association with SSRI.
The importance of this as an adverse effect of medications cannot be overemphasized, as it constitutes a barrier to depression management and often leads to poor adherence of medications. Therefore, the main objective of this study is to focus on the comparison between the two commonly used antidepressants—escitalopram and fluoxetine—on the prevalence of sexual pain among Malaysian women receiving those medications. In addition, this study also examines the correlation factors that are associated with sexual pain disorder in this group of subjects.
Methods
The ethical approval from the Ethics Committee of Universiti Kebangsaan Malaysia Medical Centre (UKMMC) was obtained prior to commence of the study.
Study Design
This is a cross-sectional study to assess and compare the prevalence of female sexual pain between treatments with fluoxetine and escitalopram. Data was collected over a period of six months, from 1st June 2009 until 30th November 2009. The study subjects were female patients on fluoxetine and escitalopram who fulfilled the inclusion criteria and attended the Psychiatric Clinic UKMMC during the study period.
Inclusion Criteria
Female outpatients who were diagnosed with major depressive disorder (MDD) based on the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) by the treating psychiatrists in UKMMC using Structured Clinical Interview for DSM-IV Disorders (SCID).
Patients who were in full remission (defined by DSM-IV as having no significant signs or symptoms of the disturbance during the past 2 months and Montgomery-Asberg depression rating scale (MADRS) score of ≤ 10).
Patients aged between 18 and 65 years old.
Patients who were married and with a sexually active partner.
Patients who were able to read and understand Malay Language (the national language).
Patients who consented.
Exclusion Criteria
Patients who were suffering from chronic and severe medical illness.
Patients who were pregnant or within 2 months postpartum period.
Sample Size
The estimated prevalence of sexual dysfunction associated with escitalopram was 30% and fluoxetine was 57.7%.8,9 A total sample of 112 subjects with 56 per group will give the power of 80% with the precision of 5% for the study.
Data Collection
Subjects of this study were identified from the psychiatric outpatient clinic, UKMMC. Written consent was obtained. Subjects were then interviewed by using the SCID Interview and the depressive symptoms were assessed with MADRS and sexual pain with the Malay Version of the Female Sexual Function Index (MVFSFI)-pain domain. The basic socio-demographic data of the subjects was collected using a predesigned questionnaire.
Instruments
Structured Clinical Interview for DSM-IV Disorders (SCID)
SCID-I is a semi-structured interview for making major DSM-IV Axis I diagnosis. This instrument was originally developed by Spitzer and colleagues.10 It is designed to be administered by experienced clinicians and is considered the standard interview to confirm diagnosis in psychiatric research. The SCID begins with a brief overview of the present illness and an enquiry about past episodes of psychopathology. Open-ended questions encourage subjects to expand their answers.
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS, developed by SA Montgomery and M Asberg, is a rating scale for the assessment of depression. The MADRS consists of 10 items that are all core symptoms of depression. Nine of the items are based upon patients’ report, and one is on the rater’s observation of the patients. Items of the MADRS are rated on a 0 to 6 scale (0 = no abnormality, 6 = severe). The rating should be based on a clinical interview. The original author found that a cut off of ≤ 10 maximized the level of agreement with the Hamilton rating scale for depression (HRSD) definition of remission.11,12
Malay Version of the Female Sexual Function Index (MVFSFI)
Female Sexual Function Index (FSFI) is a brief, multidimensional self-report measure of sexual functioning. It has been validated on a clinically diagnosed sample of women with female sexual dysfunction. It consists of 19 items and can be divided into 6 basic domains in female sexual dysfunction such as desire, subjective arousal, lubrication, orgasm, satisfaction and pain. Each of the domains has two to four questions with five to six options for patients to choose the most likely answer representing their sexual function within 4 weeks prior to the day they were given the questionnaire. Sexual pain is measured on the frequency (Q17: Over the past 4 weeks, how often did you experience discomfort or pain during vaginal penetration? and Q18: Over the past 4 weeks, how often did you experience discomfort or pain following vaginal penetration?); and degree (Q19. Over the past 4 weeks, how would you rate your level (degree) of discomfort or pain during or following vaginal penetration?) of discomfort/pain experience during sexual intercourse.13,14
The Malay Version of the Female Sexual Function Index (MVFSFI) is a validated and locally accepted questionnaire for use in the assessment of female sexual dysfunction in the Malaysian population. The cutoff score for each domain was also established for the MVFSFI.[22] In this study, the sexual pain domain of MVFSFI with the previous established cut off value of ≤ 7 (sensitivity = 86%, specificity = 95%) was used to identify female patient with sexual pain.
Dosage of Antidepressants
The current dosage of antidepressants (fluoxetine and escitalopram) was determined from the patients and the treatment records. Regarding the comparability of dosages, as stated by Cipriani et al. (2009), clear definitions about equivalence of dosages among new-generation antidepressants were not available in the published literature.15 Hence, previously published dosing classification as described by Gartlehner et al. (2007) was used in this study.16 This classification is used to detect inequalities in dosing, and does not indicate dosing equivalence.15
Dosing Classification
| Low | Medium | High | |
|---|---|---|---|
| Fluoxetine | < 30 mg/day | 30–50 mg/day | > 50 mg/day |
| Escitalopram | < 15 mg/day | 15–25 mg/day | > 25 mg/day |
Duration on Antidepressants
This referred to the period from the first day the patient was started antidepressant to the date of interview, and was determined from the patient and the treatment records. The duration was recorded to the nearest month.
Statistical Analysis
The data collected was analyzed using the Statistical Package for Social Science (SPSS) version 12 (Chicago, IL, USA). Independent t-test was used to compare the means of continuous variables with normal distribution. The normality of the distribution was tested with Kolmogorov-Smirnov test. For variables that were non-normally distributed, they were tested with Mann-Whitney U test. Chi-Square test was used to compare categorical variables. Multivariate logistic regression analysis was used to examine the association between independent variables and dependent variable. Significant variables with 10% level of significant (p value < 0.1) from univariate analysis were included into the multivariate analysis.
Results
A total of 112 female outpatients who attended the Psychiatric Clinic at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) participated in this study. There were 56 patients on fluoxetine and another 56 of them on escitalopram. None of them were on any other types of psychotropic medications.
Details of the socio-demographic characteristics of the subjects are shown in Table 1. The mean age of the subjects was 40.57 (sd = 8.79) years old with mean 15 years of marriage. For those on escitalopram, majority of the respondents were Malays (n = 29, 51.8%), and followed by the non-Malays (n = 27, 48.2%). In the fluoxetine treatment arm, the non-Malays constituted a higher percentage at 53.6% (n = 30), while the Malays were 46.4% (n = 26). There were no statistical significant differences seen in other parameters of both treatment arms, namely the education, employment, proportion of whom had menopause, smoked and consumed alcohol.
Table 1. Characteristic of the Study Subjects (N = 112).
| Treatment group | ||
|---|---|---|
| Fluoxetine | Escitalopram | |
| Age, mean (SD) | 40.32 (9.37) | 40.82 (8.24) |
| Years of marriage, mean (SD) | 14.92 (9.33) | 15.62 (8.64) |
| Race, n (%) | ||
| Malay | 26 (46.4) | 29 (51.8) |
| Non-Malay | 30 (53.6) | 27 (48.2) |
| Education, n (%) | ||
| Secondary and below | 34 (60.7) | 33 (58.9) |
| Tertiary | 22 (39.3) | 23 (41.1) |
| Employment, n (%) | ||
| Yes | 33 (58.9) | 38 (67.9) |
| No | 23 (41.1) | 18 (32.1) |
| Number of children, n (%) | ||
| < 3 | 36 (64.3) | 34 (60.7) |
| ≥ 3 | 20 (35.7) | 22 (39.3) |
| Menopause, n (%) | ||
| Yes | 12 (21.4) | 8 (14.3) |
| No | 44 (78.6) | 48 (85.7) |
| Smoking, n (%) | ||
| Yes | 8 (14.3) | 8 (14.3) |
| No | 48 (85.7) | 48 (85.7) |
| Alcohol, n (%) | ||
| Yes | 7 (12.5) | 3 (5.4) |
| No | 49 (87.5) | 53 (94.6) |
Table 2 shows the mean dosage of fluoxetine prescribed was 30.71 mg, whereas escitalopram was 12.32 mg. The mean duration of usage for both fluoxetine and escitalopram were 50.04 and 22.70 months, respectively. The escitalopram treatment arm consisted of more subjects in the low dosing class (67.9%), as compared to that of the fluoxetine group (48.2%).
Table 2. Dosage and Duration of Antidepressant Usage of the Subjects.
| Treatment group | ||
|---|---|---|
| Fluoxetine | Escitalopram | |
| Dosage, mean (sd) | 30.71 (10.76) | 12.32 (4.15) |
| Duration in months, mean (sd) | 50.04 (34.37) | 22.70 (11.87) |
| Dosing classification* | ||
| Low | 27 (48.2) | 38 (67.9) |
| High | 29 (51.8) | 18 (32.1) |
Low = (≤ 30 mg for fluoxetine or ≤ 15 mg for escitalopram).
High = (> 30 mg for fluoxetine or > 15 mg for escitalopram).
Table 3 shows that only older age, longer duration of marriage and menopause were significantly associated with female sexual pain (p < 0.01), and the prevalence was 16.1%. Other determinants such as moderate to high dosage of antidepressant, race, education level, employment status, having 3 or more children, smoking and alcohol use were all not significantly associated with female sexual pain. It is also worth noting that whether fluoxetine or escitalopram use, did not constitute to any significant association.
Table 3. Univariate Analysis of the Associated Factors for Female Sexual Pain (FSP) Based on MVFSFI.
| Female sexual pain | |||||
|---|---|---|---|---|---|
| Determinant | Present N (mean rank) | Absent N (mean rank) | Chi-Square | p value | OR (95% CI) |
| Age (years) | 18 (89.00) | 94 (50.28) | – | < 0.001*† | – |
| Marital period (years) | 18 (78.00) | 94 (52.38) | – | < 0.01*† | – |
| Antidepressant | |||||
| Fluoxetine | 10 (17.9) | 46 (82.1) | 0.265 | 0.607 | 1.304 |
| Escitalopram | 8 (14.3) | 48 (85.7) | (0.473–3.595) | ||
| Dosing | |||||
| Medium to high | 7 (10.8) | 36 (76.6) | 3.228 | 0.072 | 2.532 |
| Low | 11 (23.4) | 58 (89.2) | (0.899–7.126) | ||
| Race | |||||
| Non-Malay | 8 (14.5) | 47 (85.5) | 0.187 | 0.666 | 1.250 |
| Malay | 10 (17.5) | 47 (82.5) | (0.454–3.445) | ||
| Education | |||||
| Secondary and above | 15 (14.6) | 88 (85.4) | 2.162 | 0.157** | 0.341 |
| Primary | 3 (33.3) | 6 (66.7) | (0.077–1.513) | ||
| Employment | |||||
| No | 8 (19.5) | 33 (80.5) | 0.568 | 0.451 | 0.676 |
| Yes | 10 (14.1) | 61 (85.9) | (0.243–1.878) | ||
| No of children | |||||
| ≥ 3 | 8 (19.0) | 34 (81.0) | 0.441 | 0.506 | 1.412 |
| < 3 | 10 (14.3) | 60 (85.7) | (0.509–3.917) | ||
| Menopause | |||||
| Yes | 8 (40.0) | 12 (60.0) | 10.335 | 0.001† | 5.467 |
| No | 10 (10.9) | 82 (89.1) | (1.802–16.582) | ||
| Smoking | |||||
| Yes | 1 (6.2) | 15 (93.8) | 1.335 | 0.462** | 0.310 |
| No | 17 (17.7) | 79 (82.3) | (0.038–2.507) | ||
| Alcohol use | |||||
| Yes | 1 (10.0) | 9 (90.0) | 3.000 | 1.000** | 0.556 |
| No | 17 (16.7) | 85 (83.3) | (0.066–4.678) | ||
Analysed with Mann–Whitney Test.
Analysed with Fisher’s Exact Test.
p < 0.1.
Female HSDD = (≤ 5 in MVFSFI desire domain score), OR = Odds Ratio, CI = Confidence Interval.
The significant variables from the univariate analysis (age, years of marriage and menopause) were then included in the multivariate analysis. Table 4 shows that age was the only significant association with female sexual pain (p < 0.05), whereas, again the types of SSRI used (fluoxetine vs escitalopram) were not significantly associated with sexual pain in the Malaysian women subjects.
Table 4. Multivariate Analysis of the Associated Factors for Female Sexual Pain.
| Variables | B | SE | p value | Adjusted Odds Ratio | 95% Confidence Interval |
|---|---|---|---|---|---|
| Age (years) | 0.421 | 0.123 | 0.001* | 1.524 | 1.199–1.938 |
| Marital period (years) | −0.110 | 0.066 | 0.099 | 0.896 | 0.787–1.021 |
| Antidepressant | −0.164 | 0.638 | 0.797 | 0.849 | 0.234–2.964 |
| Fluoxetine | |||||
| Escitalopram | |||||
| Dosing | −0.993 | 0.666 | 0.136 | 0.370 | 0.100–1.367 |
| Medium to high | |||||
| Low | |||||
| Menopause | 1.577 | 1.066 | 0.139 | 4.840 | 0.599–1.938 |
| No | |||||
| Yes |
p < 0.05.
Discussions
This study was conducted with the aim to examine the prevalence of sexual pain associated with fluoxetine and escitalopram, in a group of Malaysian women at the Psychiatric Outpatient Clinic of UKMMC. By using the MVFSFI, the results showed that the prevalence of sexual pain disorder among the depressed women in remission was relatively low (16.1%). Age was found to be the only significant determinant in female sexual pain (p < 0.05). This study, albeit on small numbers, showed that neither of the antidepressants (fluoxetine and escitalopram) was of any significant association with sexual pain.
Both the fluoxetine and escitalopram groups belonged to the selective serotonin reuptake inhibitors (SSRI) antidepressant class. Most of the previous studies measured the prevalence of overall female sexual dysfunction, hypoactive sexual desire, sexual orgasm disorder and female arousal disorder, associated with SSRI, which were reported to be between 30% and 75%.8,17 However, to date, there is no study which examines the sexual pain disorder among this group of patients.
Nevertheless, the prevalence of sexual pain disorder in this study was much lower when compared to other types of sexual dysfunction associated with SSRI.17,18 Interestingly, fluoxetine and escitalopram did not correlate with sexual pain disorder in our study. We believe that few possibilities could have been the explanations of this finding. First, serotonin is one of the key neurotransmitters that have modulatory effect in the pain pathway. High level of serotonin caused by SSRI will increase its modulatory effect, such that any signals from the body are dampened, thus perceiving it as less painful. Bair et al. also explained that the deficiency of serotonin will result in depression and pain happens together because depression and painful symptoms follow the same pathways in our central nervous system.19 Second, serotonin is the neurotransmitter that mediates a sense of satisfaction in behaviors ranging from eating to sexual arousal. Therefore, increased level of brain serotonin with SSRI will inhibit orgasm and reduce sexual desire,20 thus may have also reduced the perception of pain. Third, the small sample size in this study may have limited the power to detect statistically significant differences.
The results of older age and menopause being associated with higher risk of sexual pain were in fact consistent with the previous studies.21,22 In this study, multivariate logistic regression analysis revealed that age is the only predictor for the sexual pain disorder. As we mentioned before, physiologically, as women aged, they eventually attain menopause. Menopause is characterized by a decrease in circulating oestrogen levels, resulting in a majority of women with some degree of change in sexual function. Alterations in the genital sensation, blood flow and the acidic environment in the vaginal canal are found to be highly correlated with the increased risk of having sexual pain.1 Furthermore, as women start to age, they will have higher chance to develop atherosclerotic disease because of lack of vascular protection from the sex hormone. Thus, the symptoms of vaginal dryness and dyspareunia may arise, due to diminished pelvic blood flow which leads to vaginal wall and clitoral smooth muscle fibrosis.23 Besides, when the pelvic floor muscles become hypertonic, vaginismus can develop leading to dyspareunia and other sexual pain disorders.1
In this study, there were several limitations which needed to be highlighted here. First, the sample size was relatively small, whereby only 112 Malaysian women were studied. Second, this was a comparative cross-sectional study done only at a selected urban center (UKMMC), thus this might limit the generalizability of the findings from this study. Also, this cross-sectional study could only determine an association, and not a causal effect. Finally, females are more reserved in our culture and the relationship of the subjects with their husbands was not investigated here. Thus, despite even good rapport had been established with the patients, they might still be less likely to discuss such sensitive subjects openly and therefore might have influence on the figures. It could also be that the general clinic settings did not provide desired level of privacy for such sensitive discussion, with the presence of nurses, attendants and even medical students.
Conclusions
In this study, it was demonstrated that both fluoxetine and escitalopram were not associated with increase in prevalence of sexual pain in Malaysian women. However, it was shown that patients in older age group and those who had menopause were more at risk of having sexual pain. Since there is no significant difference in the prevalence of sexual pain in women on both the SSRIs, there should not be any barrier when continuing the use of escitalopram or fluoxetine as antidepressants amongst the female patients.
Footnotes
FUNDING
None.
CONFLICT OF INTEREST
None.
References
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