Anita H. Clayton

Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women.

Abstract: Premenopausal women meeting operational criteria for idiopathic, acquired, global hypoactive sexual desire disorder were studied in a randomized, double-blind, placebo-controlled, multiple-site escalating dose 112-day trial of bupropion sustained release. Outcome was measured by investigator-rating and self-administered questionnaires. All measures indicated greater sexual responsiveness in women receiving bupropion. The Changes in Sexual Functioning Questionnaire indicated that bupropion had significant effects on increasing measures of sexual arousal, orgasm completion, and sexual satisfaction.

Reliability and Construct Validity of the Changes in Sexual Functioning Questionnaire Short-Form (CSFQ-14)

The Changes in Sexual Functioning Questionnaire (CSFQ) is a 36-item clinical and research instrument identifying five scales of sexual functioning. This study documents the internal consistency and factor structure of a 14-item version of the CSFQ (CSFQ-14), which yields scores for three scales corresponding to the phases of the sexual response cycle (i.e., desire, arousal, and orgasm) as well as the five scales of the original CSFQ. Factor analysis confirms the construct validity of the CSFQ-14 as a global measure of sexual dysfunction. The CSFQ-14 and the individual scales exhibit strong internal reliability.

Reliability and Validity of the Sexual Interest and Desire Inventory–Female (SIDI-F), a Scale Designed to Measure Severity of Female Hypoactive Sexual Desire Disorder

The Sexual Interest and Desire Inventory–Female (SIDI-F) is a 13-item scale developed as a clinician-administered assessment tool to quantify the severity of symptoms in women diagnosed with hypoactive sexual desire disorder (HSDD). The present investigation assessed the reliability and validity of the SIDI-F as a measure of HSDD severity. Results show that the SIDI-F exhibits excellent internal consistency, with Cronbachs alpha of 0.9. The validity of the SIDI-F as a measure of HSDD severity was confirmed by a number of observations. Women with a clinical diagnosis (Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR; American Psychiatric Association, 2000]) of HSDD had significantly lower SIDI-F scores than women not meeting diagnostic criteria for any subtype of female sexual dysfunction and women diagnosed with female orgasmic disorder. There was a high correlation between scores on the SIDI-F and scores on the Female Sexual Function Index (FSFI; Rosen et al., 2000) and an interactive voice response version of the Changes in Sexual Functioning Questionnaire (CSFQ; Clayton, McGarvey, & Clavet, 1997; Clayton, McGarvey, Clavet, & Piazza, 1997), two validated measures that assess general female sexual dysfunction. In contrast, there was a poor correlation between SIDI-F scores and scores on a slightly modified Marital Adjustment Scale (Locke, Wallace, 1959; MAS), an assessment of general (nonsexual) relationship satisfaction. Taken together, the results of the present investigation indicate that the SIDI-F is a reliable and valid measure of HSDD severity, independent of relationship issues.

REVIEWS: Proposal for Changes in Diagnostic Criteria for Sexual Dysfunctions

INTRODUCTION Officially sanctioned diagnostic criteria have a major influence on treatment decisions and on how populations are defined for clinical research. The Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association has had a major influence on research concerning the treatment of sexual disorders and has been criticized on numerous grounds. AIM The purpose of this article is to describe the evolution of criteria sets in the DSM and to critically evaluate suggestions for modification of this system. METHOD All living members of the DSM work groups on sexual dysfunction were contacted regarding their recollections of the evolution of criteria sets. Literature concerning diagnostic criteria for the sexual dysfunctions in the DSM, as well as literature suggesting modification of this system, was reviewed. MAIN OUTCOME MEASURE Recommendations for changes in the DSM-V system were based upon a review of the evidence concerning optimal criteria for each diagnostic entity. RESULTS The original diagnostic system from sexual disorders in the DSM was developed by expert opinion, literature searches, and solicitation of feedback for other experts in the field. There have been minimal changes in the DSM criteria for sexual dysfunctions because of the requirement that there be substantial empirical data before modification of the system would be considered. An international consensus group has suggested major modification in criteria concerning female sexual dysfunctions. There is a growing database that documents the need to change criteria for premature ejaculation. CONCLUSIONS It is recommended that some of the suggested modifications to the criteria sets for sexual dysfunctions be adopted by the DSM-V committee. It is also recommended that specific criteria related to duration and severity be adopted, in order to clearly distinguish sexual disorders from transient alterations in sexual function related to life stress and relationship discord.

Serotonin 2A -1438 G/A and G-protein beta3 subunit C825T polymorphisms in patients with depression and SSRI-associated sexual side-effects

The occurrence of sexual side-effects from antidepressants is thought to be mediated through serotonin 2A (5HT2A) receptors. It is currently unknown if functional polymorphisms in the 5HT2A receptor or its G-protein second messenger complex are related to sexual dysfunction in patients taking an selective serotonin reuptake inhibitor (SSRI) for depression. The purpose of this study was to determine the relationship of the 5HT2A −1438 G/A and GNB3 C825T single nucleotide polymorphisms with overall sexual well-being and individual components of sexual health as measured by the Changes in Sexual Functioning Questionnaire (CSFQ). We evaluated 89 outpatients (18–40 years of age) at low risk for other causes of sexual dysfunction who were being treated for depression with an SSRI and did not have sexual difficulties before taking the antidepressant. Outcome measures were stratified by 5HT2A and GNB3 genotypes. After controlling for age, gender, anxiety scale scores, and depression scale scores, persons with a GG genotype of the 5HT2A −1438 single nucleotide polymorphisms (SNP) were significantly more likely to be categorized as having sexual dysfunction than persons with a GA or AA genotype (OR=3.6; 95% CI 1.03, 12.6; p=0.046). Furthermore, the 5HT2A −1438 GG genotype was a significant predictor of lower arousal scores (p=0.022) after accounting for other measures. There was no significant relationship between any outcome measure and GNB3 genotype.

A double-blind comparison between bupropion XL and venlafaxine XR : Sexual functioning, antidepressant efficacy, and tolerability

Abstract: In this double-blind, multicenter study, bupropion XL, a norepinephrine-dopamine reuptake inhibitor, and venlafaxine XR, a serotonin-norepinephrine reuptake inhibitor, were compared with regard to sexual functioning, efficacy, and tolerability. A total of 348 sexually active adult outpatients with depression were randomized to receive bupropion XL (titrated to a target dose of 300-450 mg/d) or venlafaxine XR (titrated to a target dose of 150-225 mg/d) for 12 weeks. Total scores on the primary dependent variable, the Changes in Sexual Functioning Questionnaire (self-report), increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR; the mean change scores differed significantly between groups from week 2 onward. Among subjects with normal pretreatment sexual functioning, Changes in Sexual Functioning Questionnaire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group; mean change scores also differed between groups from week 2 onward. Although the therapies resulted in similar change on the 17-item Hamilton Depression Rating Scale, remission rates were significantly higher among those treated with bupropion XL (46%) versus venlafaxine XR (33%) (odds ratio, 1.93; 95% confidence interval, 1.07-3.46). Aside from adverse effects of venlafaxine XR on sexual function, both treatments were reasonably well tolerated. In conclusion, in this patient population (ie, relatively young, sexually active outpatients), bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile.

Distressing sexual problems in United States women revisited: prevalence after accounting for depression.

OBJECTIVE With data from the population-based Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE) study, which has previously estimated the prevalence of sexual problems and sexually related personal distress in United States women, the prevalence of sexual disorders of desire, arousal, and orgasm was re-estimated, taking concurrent depression into consideration. METHOD Current depression was defined in 3 ways as (1) self-reported symptoms alone, (2) antidepressant medication use alone, or (3) symptoms and/or antidepressant use. The unadjusted population prevalence for each distressing sexual problem in the 31,581 respondents was calculated first irrespective of concurrent depression and then in women without concurrent depression, thus determining the size of the population with both conditions present. RESULTS The unadjusted population-based prevalence of desire disorder was 10.0% and was reduced to 6.3% for those without concurrent depression, leading to an estimate of 3.7% for those with both conditions present. The same pattern was observed for arousal and orgasm disorders, although overall prevalence estimates were lower. CONCLUSIONS Our findings indicate that about 40% of those with a sexual disorder of desire, arousal, or orgasm have concurrent depression, As this study was cross-sectional, causality versus comorbidity cannot be determined. However, our findings stress the importance of evaluating depression along with sexual problems in routine clinical practice and epidemiology research.

Sexual function and dysfunction in women

Multiple factors may affect sexual functioning in women, requiring a thorough assessment of all possible etiologies to guide appropriate treatment. Interventions may also be multifaceted, ranging from sex education to psychotherapy to medical treatment. Restoration of sexual functioning is the goal of treatment, but more research is needed for true success to be realized.

Continuing Medical Education: The Impact of Mental Illness and Psychotropic Medications on Sexual Functioning: The Evidence and Management (CME)

BACKGROUND Sexual dysfunction (SD) occurs frequently in patients with psychiatric illness. METHODS The published literature on SD in patients with a psychiatric illness and/or taking psychotropic medications was reviewed. RESULTS SD prevalence and type was found to vary with the specific psychiatric illness and medication treatment. Assessment is complicated by the presence of preexisting or comorbid sexual disorders or medical illness affecting sexual function. Direct questioning about sexual function before treatment and throughout the course of therapy is essential to establish baseline sexual functioning, patient preferences regarding medication side effects, and to identify medication-associated SD. A limited number of management strategies for SD in psychiatric patients have been systematically studied. CONCLUSIONS SD with psychiatric illness and its treatment requires early identification, and incorporation of patient preferences for successful management.

An integrated analysis of the safety and tolerability of desvenlafaxine compared with placebo in the treatment of major depressive disorder

INTRODUCTION The safety and tolerability profiles of antidepressants can often influence the treatment choices of clinicians treating major depressive disorder. The purpose of this investigation was to characterize the safety and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) in treating depression. METHODS An integrated analysis of all short-term, randomized, double-blind, placebo-controlled registration studies for major depressive disorder (four flexible-dose and five fixed-dose studies) was performed. Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks. Treatment-emergent adverse events, laboratory values, vital signs, and discontinuation symptoms were evaluated. In the subset of fixed-dose studies, dose-related effects were analyzed. RESULTS In the overall population (placebo: n=1,116; desvenlafaxine: n=1,834), adverse events resulted in discontinuations in 3% of placebo-treated patients and 12% of desvenlafaxine-treated patients; in the subset of fixed-dose studies, the rates were 4% with placebo and increased with desvenlafaxine dose (50 mg/day: 4%; 400 mg/day: 18%). The most common treatment-emergent adverse event was transient nausea that was generally mild to moderate. The most common sexual dysfunction associated with desvenlafaxine treatment was erectile dysfunction in men (7% vs 1% with placebo) and anorgasmia in women (1% and 0%). One desvenlafaxine-treated patient died of a completed suicide; there were four suicide attempts (three desvenlafaxine, one placebo) and eight cases of suicidal ideation (five desvenlafaxine, three placebo) during the on-therapy period. Small but statistically significant changes in mean blood pressure occurred at all desvenlafaxine doses; clinically meaningful changes were observed in 1% of placebo-treated patients and 2% of desvenlafaxine-treated patients. Desvenlafaxine was associated with small but statistically significant mean changes in laboratory assessments, particularly lipid and liver enzyme elevations, and electrocardiograms; few cases of these changes were clinically relevant. CONCLUSION Desvenlafaxine in the treatment of major depressive disorder exhibited a safety and tolerability profile generally consistent with the serotonin-norepinephrine reuptake inhibitor class. The most common adverse event was transient nausea. At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo.