Factorial Trial to Optimize an Internet-Delivered Intervention for Sexual Health After Breast Cancer: Protocol for the WF-2202 Sexual Health and Intimacy Enhancement (SHINE) Trial.

BACKGROUND: Although most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake. OBJECTIVE: Guided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention components. This study aims to determine how intervention components work (mediators) and for whom they work best (moderators). METHODS: Partnered, posttreatment adult female survivors of breast cancer (N=320) experiencing at least 1 bothersome sexual symptom (ie, pain with sex, vaginal dryness, low sexual desire, and difficulty with orgasm) related to their breast cancer treatment will be enrolled. Clinic-based recruitment will be conducted via the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participants will be randomly assigned to 1 of 16 combinations of four intervention components with two levels each in this factorial trial: (1) psychoeducation about cancer-related sexual morbidity (receive either enhanced vs standard versions); (2) communication skills training for discussing concerns with health care providers (received vs not received); (3) communication skills training for discussing concerns with a partner (received vs not received); and (4) intimacy promotion skills training (received vs not received). Cores will be fully automated and implemented using a robust internet intervention platform with highly engaging elements such as animation, video, and automated email prompts. Survivors will complete web-based assessments at baseline (prerandomization time point) and again at 12 and 24 weeks later. The primary study aim will be achieved through a decision-making process based on systematically evaluating the main and interaction effects of components on sexual distress (Female Sexual Distress Scale-Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Index) using a generalized linear model approach to ANOVA with effect coding. Mediation analyses will be conducted through a structural equation modeling approach, and moderation analyses will be conducted by extending the generalized linear model to include interaction effects. RESULTS: This protocol has been reviewed and approved by the National Cancer Institute Central Institutional Review Board. Data collection is planned to begin in March 2024 and conclude in 2027. CONCLUSIONS: By identifying the combination of the fewest and least-intensive intervention components likely to provide survivors of breast cancer the greatest sexual health benefit, this study will result in the first internet intervention that is optimized for maximum impact on the undertreated, prevalent, and distressing problem of breast cancer-related sexual morbidity. TRIAL REGISTRATION: ClinicalTrials.gov NCT06216574; https://clinicaltrials.gov/study/NCT06216574. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57781.

Including partners in discussions of sexual side effects from breast cancer: a qualitative study of survivors, partners, and providers.

PURPOSE: Ensuring there are clear standards for addressing cancer-related sexual side effects is important. Currently, there are differences in two leading sets of clinical guidelines regarding the inclusion of survivors' romantic partners into clinical discussions between survivors and their providers about this issue. To help refine guidelines, we examine breast cancer survivor, partner, and oncology provider perspectives about including partners in discussions about cancer-related sexual side effects in a secondary analysis of a broader qualitative study. METHODS: Partnered female breast cancer survivors (N = 29) completed online surveys, and intimate partners of breast cancer survivors (N = 12) and breast oncology providers (N = 8) completed semi-structured interviews. Themes were derived from thematic content analysis. RESULTS: Among survivors who reported a discussion with their provider, fewer than half indicated their partner had been present, despite most survivors expressing it was - or would have been - helpful to include their partner. Partners also largely indicated being included was or would have been helpful, when welcomed by the survivor. Providers similarly emphasized the importance of survivors' autonomy in deciding whether to discuss sexual concerns in the presence of a partner. CONCLUSIONS: Partners were infrequently included in conversations about cancer-related sexual side effects, even though survivors, partners, and providers alike expressed value in these discussions occurring with the couple together - when that is the survivor's preference. Findings suggest future clinical guidelines should emphasize that incorporating partners into clinical discussions about sexual concerns is important for many breast cancer patients. Soliciting and enacting patients' preferences is essential for truly patient-centered care.

The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women.

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Addressing sexual concerns of female breast cancer survivors and partners: a qualitative study of survivors, partners, and oncology providers about Internet intervention preferences.

PURPOSE: Sexual side effects after breast cancer treatment are common and distressing to both survivors and their intimate partners, yet few receive interventions to address cancer-related sexual concerns. To direct intervention development, this qualitative study assessed the perceptions of female breast cancer survivors, intimate partners of breast cancer survivors, and breast cancer oncology providers about how an Internet intervention for couples may address breast cancer-related sexual concerns. METHODS: Survivors (N = 20) responded to online open-ended surveys. Partners (N = 12) and providers (N = 8) completed individual semi-structured interviews. Data were inductively coded using thematic content analysis. RESULTS: Three primary intervention content areas were identified by the key stakeholder groups: (1) information about and strategies to manage physical and psychological effects of cancer treatment on sexual health, (2) relationship and communication support, and (3) addressing bodily changes and self-image after treatment. Survivors and partners tended to express interest in some individualized intervention private from their partner, although they also emphasized the importance of opening communication about sexual concerns within the couple. Survivors and partners expressed interest in an intervention that addresses changing needs across the cancer trajectory, available from the time of diagnosis and through survivorship. CONCLUSION: Internet intervention for couples to address cancer-related sexual concerns, particularly one that provides basic education about treatment side effects and that evolves with couples' changing needs across the cancer trajectory, was perceived as a valuable addition to breast cancer care by survivors, partners, and providers.

Instruments for Screening, Diagnosis, and Management of Patients with Generalized Acquired Hypoactive Sexual Desire Disorder.

Screening, diagnosis, and management of hypoactive sexual desire disorder (HSDD) and research into the condition have been challenging due to its biopsychosocial complexity and lack of consensus on relevant measures. Although physician interviews yield much clinically valid information, self-reported questionnaires appear more acceptable to patients and physicians. Consequently, validated patient-reported outcome (PRO) tools are essential for evaluation and management of HSDD, including any therapeutic intervention. The US Food and Drug Administration (FDA) has issued guidance on the use of appropriate endpoints and associated measures for female sexual dysfunction, including HSDD. Although many of the available measures were not designed specifically for HSDD assessment, as per FDA guidelines, most clinical studies have used individual domains or items from established tools, such as the Female Sexual Function Index-desire domain and Item 13 of the revised Female Sexual Distress Scale. For clinical practice, several professional societies recommend the Decreased Sexual Desire Screener and/or a sexual history as tools to diagnose HSDD. This review discusses frequently used PRO tools as well as the newly developed and validated Elements of Desire Questionnaire, which may be appropriate for clinical trials or clinical practice.

Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women.

INTRODUCTION: Prior medication treatment for hypoactive sexual desire disorder (HSDD) in women has left about half the subjects without benefit. Lorexys (LOR), a proprietary combination of the stimulating/excitatory dopamine-norepinephrine reuptake inhibitor bupropion (BUP) and the sedating/inhibitory serotonergic agonist-antagonist trazodone (TRZ), was developed as a multifunctional solution for this problem. AIM: Test efficacy, safety, and tolerability of LOR in a range of doses in a combined phase IB/IIA study in premenopausal outpatients with HSDD. METHODS: Otherwise healthy premenopausal women from 25-50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release TRZ and/or sustained-release BUP. Evaluations were made before and after each treatment. A washout of at least a week followed each treatment. The order of treatments was a standard dose of BUP; a subtherapeutic dose of BUP and TRZ (LOR-low); and a threshold-therapeutic dose of BUP and TRZ (LOR-mod). A midpoint interim analysis was planned to consider adapting doses for efficacy or safety. MAIN OUTCOME MEASURE: The primary efficacy measure was the Female Sexual Function Index, Desire domain; the main secondary efficacy measures included the Female Sexual Distress Scale-Revised 13th item, on bother about low desire, and a Patient's Global Impression of Change. The main outcome comparison was the proportions of responders. Safety measures were elicited adverse events, Epworth Sleepiness Scale, Columbia Suicide Severity Rating Scale 6-item SCREEN version, vital signs, electrocardiograms, and standard laboratory tests. RESULTS: Interim analysis did not require altering doses. Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale-Revised Item 13, and 79% on Patient's Global Impression of Change; each P < .05 vs BUP). As expected, close to half responded to BUP (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of TRZ, but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale. CLINICAL IMPLICATIONS: The open-label 1-way crossover design of this phase IB/IIA study limits conclusions, but the consistency of responder analyses showing superiority of LOR-mod dose over control, and the lack of central depressant dropouts, favor further development in double-blind placebo-control trials. STRENGTH & LIMITATIONS: Strengths include large margins of efficacy over control agent, rapid onset of action, and rigorous safety assessment. Limitations are open-label, cross-over design/lack of placebo control and 1-month duration of exposure. CONCLUSION: Moderate-dose LOR was generally well-tolerated and was significantly more effective than BUP (active control). The results seem highly favorable compared to previously tested agents. Pyke RE, Clayton AH. Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women. J Sex Med 2019;16:1885-1894.

Lumping, Splitting, and Treating: Therapies Are Needed for Women With Overlapping Sexual Dysfunctions.

INTRODUCTION: Phase-specific diagnoses, such as hypoactive sexual desire disorder, are the norm in sexual medicine. Epidemiologic surveys and clinical trials show the value of this structure for understanding and treating premenopausal sexual dysfunction; however, postmenopausal women have sexual dysfunction in >1 phase, for example, in desire and arousal. OBJECTIVE: To evaluate the evidence for mixed or global sexual dysfunction in women, identify associated comorbidities, and determine the best available treatment. METHODS: Literature review of epidemiologic surveys and clinical trials to quantitate overlap in sexual dysfunction and render conclusions about treatments. MAIN OUTCOME MEASURES: The main outcome measures were the Changes in Sexual Functioning Questionnaire and the Female Sexual Function Index. RESULTS: Overlap of sexual dysfunction in women is low to moderate before menopause, but it is high after menopause. Data suggest that clinical trials of postmenopausal women diagnosed with hypoactive sexual desire disorder actually entered patients with mixed or global sexual dysfunction and that benefits were pan-phasic rather than concentrated on desire. Whether local/vaginal products for the genitourinary syndrome of menopause impact all phases of sexual dysfunction is under study. Women treated for breast or gynecologic cancer or taking antidepressants also have global sexual dysfunction. Treatment options are limited but support mindfulness-based cognitive behavioral therapy and others. Other strategies include adding or switching to a serotonin 1A receptor agonist (eg, buspirone, flibanserin), a serotonin 2A receptor antagonist (eg, flibanserin, trazodone), or a norepinephrine-dopamine reuptake inhibitor (eg, bupropion). Elimination of hormonal contraception in premenopausal women and adding hormonal therapies in postmenopausal women may be necessary. CONCLUSIONS: Practitioners should be alert to overlap of sexual dysfunction in women. Focusing diagnostics and treatment on individual phases of sexual function is appropriate in premenopausal patients, but global sexual dysfunction is more likely in women taking antidepressants or cancer chemotherapy or during and after the menopausal transition. More safe, broadly effective treatments for mixed sexual dysfunction are needed for these populations of women. Pyke RE, Clayton AH. Lumping, Splitting, and Treating: Therapies Are Needed for Women With Overlapping Sexual Dysfunctions. Sex Med Rev 2019;7:551-558.

Comparison of adjunctive use of aripiprazole with bupropion or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors: analysis of patients beginning adjunctive treatment in a 52-week, open-label study.

BACKGROUND: This post hoc analysis assessed the safety, tolerability and effectiveness of long-term treatment with aripiprazole adjunctive to either bupropion or selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). METHODS: Data from de novo patients (did not participate in 2 previous studies) in a 52-week, open-label safety study of adjunctive aripiprazole after documented inadequate response to 1-4 antidepressant treatments (ADTs; SSRI, SNRI, or bupropion) were analyzed post hoc. Assessments included safety and tolerability, sexual functioning (Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI]) and Clinical Global Impressions-Severity (CGI-S). RESULTS: Forty-seven patients received bupropion plus aripiprazole and 245 received an SSRI/SNRI plus aripiprazole; 19 (40.4%) and 78 (31.8%), respectively, completed 52 weeks of treatment, and 46 and 242, respectively, received ≥1 dose of study medication (safety sample). Median time to discontinuation (any reason) was 184.0 days. Overall, 97.8% of patients in the bupropion group and 93.8% in the SSRI/SNRI group experienced ≥1 adverse event. The most common treatment-emergent adverse events were fatigue (26.1%) and somnolence (21.7%) with bupropion and fatigue (23.6%) and akathisia (23.6%) with an SSRI/SNRI. Mean change in body weight at week 52 (observed cases) was +3.1 kg for bupropion and +2.4 kg for an SSRI/SNRI. Treatment-emergent, potentially clinically relevant abnormalities in fasting glucose occurred in 8.3% of patients with bupropion and 17.4% with an SSRI/SNRI; for abnormalities in fasting total cholesterol, the incidence was 25.0% and 34.7%, respectively. Mean (SE) change from baseline in fasting glucose was 1.4 (1.9) mg/dL with bupropion and 2.7 (1.5) mg/dL with an SSRI/SNRI. Baseline MGH-SFI item scores indicated less severe impairment with bupropion versus an SSRI/SNRI; in both groups most MGH-SFI items exhibited improvement at week 52. Mean CGI-S improvement at week 52 (last observation carried forward) was -1.4 with bupropion and -1.5 with an SSRI/SNRI (efficacy sample). CONCLUSIONS: There were no unexpected AEs with long-term adjunctive aripiprazole therapy when added to either bupropion or SSRIs/SNRIs, and symptom improvement was similar between ADT groups. Sexual functioning in patients with MDD on antidepressants was also modestly improved after adding aripiprazole. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00095745 (November 9, 2004).

Validity of the decreased sexual desire screener for diagnosing hypoactive sexual desire disorder.

The decreased sexual desire screener is a brief diagnostic instrument for generalized acquired hypoactive sexual desire disorder in women. During the screening visit of 2 clinical trials, the authors assessed sensitivity of the decreased sexual desire screener in premenopausal women presenting with decreased sexual desire. The authors compared diagnoses of generalized acquired hypoactive sexual desire disorder made by clinicians who were not trained or specialized in the diagnosis of female sexual dysfunction using the decreased sexual desire screener with diagnoses made by expert clinicians after an extensive diagnostic interview. The sensitivity of the decreased sexual desire screener was 0.946 in a North American trial and 0.960 in a European trial.

Sexual function in women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrinologic disorder. Little is known about the effects of PCOS on overall sexual functioning, phases of the sexual response cycle, and sexual satisfaction. AIM: To compare the differences in sexual function between women with PCOS and controls, and to assess the relationship of serum testosterone, body mass index (BMI), hirsutism, and acne with sexual function scores in women with PCOS. METHODS: A cross-sectional analysis in which women who met the National Institute of Child Health and Human Development criteria for PCOS were compared with a group of healthy volunteers. MAIN OUTCOME MEASURES: Results from the validated Changes in Sexual Functioning Questionnaire (CSFQ) were used to assess sexual function. In women with PCOS, serum testosterone levels, BMI, self-reported hirsutism, and acne were assessed as independent variables. RESULTS: Ninety-two women with PCOS and 82 controls were studied. Based on total CSFQ scores, sexual dysfunction was present in 27.2% of cases vs. 24.4% of controls (not signifcant). Women with PCOS had a significantly lower orgasm/completion score compared with women in the control group (P < 0.001). Women with PCOS whose testosterone levels were >1 standard deviation above the mean had significantly better sexual functioning vs. those within 1 SD (P = 0.015) and those >1 SD below the mean (P = 0.033). In women with PCOS, increasing BMI was associated with a significant reduction in the orgasm/completion subdomain, but no significant associations were found in regard to acne or hirsutism. CONCLUSIONS: Women with PCOS have similar sexual functioning scores compared with controls except in regard to orgasm/completion. The subpopulation of women with PCOS whose serum testosterone levels are in the normal reproductive range are at increased risk for sexual dysfunction.

Menopausal status in breast cancer patients with past chemotherapy determines long-term hypoactive sexual desire disorder.

INTRODUCTION: Chemotherapy and endocrine treatment in young breast cancer patients are frequently associated with abrupt menopause. Little is known about the long-term prevalence of hypoactive sexual desire disorder (HSDD) in these patients. AIMS: To examine the effects of adjuvant endocrine therapy on sexual desire in premenopausal patients with breast cancer and past chemotherapy. METHODS: A controlled, cross-sectional study enrolled 47 women with breast cancer or benign breast disease at a tertiary care center. A standardized questionnaire (Sexual Interest and Desire Inventory-Female; SIDI-F) on HSDD was utilized. Serum concentrations for estradiol were measured by a specific assay. MAIN OUTCOME MEASURES: The SIDI-F interview was applied in 35 women with breast cancer (mean age: 42.3 years) with eventual adjuvant endocrine therapy, 2-8 years after chemotherapy, and 13 women with benign breast tumors (mean age: 39.8 years), 2-5 years after diagnosis. RESULTS: Mean SIDI-F scores were similar in the breast cancer group (32.9) and the benign breast disease group (34.0). Subgroup analysis revealed no statistical differences in the mean SIDI-F scores with respect to the actual endocrine therapy. However, in breast cancer patients with menopause induced by chemotherapy or gonadotropin-releasing hormone (GnRH) agonists, the SIDI-F scores were significantly lower (30.7) compared to breast cancer patients with menorrhea (40.4). In breast cancer patients, amenorrhea was associated with significantly lower estradiol levels compared to menorrhea (24 pg/mL vs. 91 pg/mL; P = 0.02). CONCLUSIONS: Cancer treatment that leads to long-term ovarian failure in breast cancer patients has a negative impact on sexual desire. Patients with menopause induced by chemotherapy or GnRH agonists show significantly reduced sexual desire as compared to menstruating patients with past chemotherapy.

Validation of the decreased sexual desire screener (DSDS): a brief diagnostic instrument for generalized acquired female hypoactive sexual desire disorder (HSDD).

INTRODUCTION: An accurate diagnosis of Hypoactive Sexual Desire Disorder (HSDD) currently relies on a time-consuming interview with an expert clinician. Limited access to such expertise means that many women with HSDD remain undiagnosed. The Decreased Sexual Desire Screener (DSDS) was developed to provide clinicians who are neither trained nor specialized in Female Sexual Dysfunction (FSD) with a brief diagnostic procedure for the diagnosis of generalized acquired HSDD in women. METHODS: A prospective non-treatment multicenter study enrolled 263 women at 27 centers in North America in order to test the validity of the DSDS for diagnosing generalized acquired HSDD in women. Subjects completed the DSDS at the screening visit and their answers were reviewed with a clinician who was not an expert in FSD ("non-expert clinician"). Separately and while being unaware of the non-expert clinician's diagnosis, an expert clinician conducted a standard diagnostic interview. MAIN OUTCOME MEASURES: Diagnostic outcomes (generalized acquired HSDD or not) were compared. Primary endpoints included the sensitivity and specificity of the DSDS relative to the standard diagnostic interview. Subject and non-expert clinician debriefing were obtained via a written, structured interview. This ensured that a large sample could be tested under uniform conditions across multiple sites. RESULTS: Diagnostic assessment by DSDS and standard diagnostic interview were in agreement in 85.2% (224/263) of cases, with the sensitivity and specificity of the DSDS 83.6% and 87.8%, respectively. Debriefing showed that the five DSDS questions were well understood by 85.4% (76/89) of subjects included in the debriefing exercise, while non-expert clinicians considered the DSDS questions adequate to diagnose HSDD in 92.9% (235/253) of cases. CONCLUSIONS: The DSDS is a sensitive and specific brief diagnostic instrument for generalized acquired HSDD in women that is quick and easy to use.

Relative antidepressant efficacy of bupropion and the selective serotonin reuptake inhibitors in major depressive disorder: gender-age interactions.

To determine whether age/gender-based differences in efficacy exist between bupropion and the selective serotonin reuptake inhibitors for major depressive disorder, we pooled the findings of 10 double-blind studies comparing bupropion with a selective serotonin reuptake inhibitor. Men (N=943) and women (N=1179) were divided into three age groups (younger than 40, 40-55, older than 55). Improvement in terms of the 17-item Hamilton Depression Rating Scale, as well as the Bech melancholia, anxiety-somatization, and insomnia factors of the Hamilton Depression Rating Scale was compared between the two treatment groups. Of 64 pair-wise comparisons, only one was statistically significant. Specifically, more women treated with a selective serotonin reuptake inhibitor experienced a 50% or greater decrease in Hamilton Depression Rating Scale Anxiety-Somatization scores (58.8 versus 63.8%, P=0.0394). No difference, however, was seen in the degree of resolution of Hamilton Depression Rating Scale Anxiety-Somatization scores (continuous measure) between women treated with bupropion versus a selective serotonin reuptake inhibitor (P=0.114). Bupropion and the selective serotonin reuptake inhibitors, thus, appear to be equally effective in treating depressive symptoms, as well as anxious/somatic symptoms and insomnia in depression. No gender-related or age-related differences were found except that greater improvement was seen in anxious/somatic symptoms of depression among women during selective serotonin reuptake inhibitor treatment. This finding could, however, not be replicated when improvement in anxious/somatic symptoms was defined as a continuous measure.

Extended-release bupropion: an antidepressant with a broad spectrum of therapeutic activity?

Bupropion, a noradrenaline and dopamine re-uptake inhibitor, has long been indicated for the treatment of depression. Recent studies have demonstrated additional benefits in depression, including: prevention of the recurrence of seasonal affective disorder in depressive subtypes with decreased energy, pleasure and interest; in major depression with concomitant anxiety; in elderly depressed patients; for non-response to initial serotonin re-uptake inhibitor therapy or augmentation of partial efficacy with serotonin re-uptake inhibitors; and in bipolar depression. Efficacy in other conditions has also been shown in studies of attention deficit hyperactivity disorder, nicotine dependence, obesity and hypoactive sexual desire disorder. Thus, bupropion has proven effective across a broad spectrum of depressive conditions, subtypes and comorbidities.

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

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.

Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies.

OBJECTIVE: To compare the effects on sexual functioning and the antidepressant efficacy of once-daily bupropion extended release (XL) and escitalopram in adults with major depressive disorder (MDD). METHOD: Adult outpatients with moderate to severe DSM-IV-defined MDD and normal sexual functioning were randomly assigned to receive bupropion XL (300-450 mg/day; N = 276), escitalopram (10-20 mg/day; N = 281), or placebo (N = 273) for up to 8 weeks in 2 identically designed, randomized, double-blind, parallel-group studies (study 1 conducted from February 6, 2003, to June 10, 2004; study 2 conducted from January 21, 2003, to June 15, 2004). Data were analyzed prospectively for each study individually, and pooled data were analyzed retrospectively. RESULTS: In both the individual studies and the pooled dataset, the incidence of orgasm dysfunction at week 8 (primary endpoint) and the incidence of worsened sexual functioning at the end of the treatment period were statistically significantly lower with bupropion XL than with escitalopram (p < .05), not statistically different between bupropion XL and placebo (p > or = .067), and statistically significantly higher with escitalopram than with placebo (p < or = .001). The percentages of patients with orgasm dysfunction at week 8 in study 1, study 2, and the pooled dataset, respectively, were 13%, 16%, and 15% with bupropion XL; 32%, 29%, and 30% with escitalopram; and 11%, 8%, and 9% with placebo. The respective percentages of patients with worsened sexual functioning at the end of the treatment period were 18%, 22%, and 20% with bupropion XL; 37%, 34%, and 36% with escitalopram; and 14%, 16%, and 15% with placebo. Mean changes in Changes in Sexual Functioning Questionnaire scores for all domains at week 8 were statistically significantly worse for escitalopram compared with bupropion XL (p < or = .05). Separation from placebo could not be established at a statistical .05 level for bupropion on 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. However, escitalopram showed statistical superiority to placebo on HAM-D-17 total score in one of the 2 studies and in the pooled data. Bupropion XL did not statistically differ from escitalopram with respect to mean change in HAM-D-17 total score, HAM-D-17 response or remission rates, percentage of patients much or very much improved on Clinical Global Impressions-Improvement scale scores, or mean changes in the Hospital Anxiety and Depression (HAD) scale total score or Clinical Global Impressions-Severity of Illness scale score at week 8. CONCLUSIONS: Bupropion XL had a sexual tolerability profile significantly better than that of escitalopram with similar HAM-D-17 remission rates and HAD total scores in patients with MDD.

Major depressive disorder, antidepressants, and sexual dysfunction.

Sexual dysfunction is a common problem with a number of causes, including psychosocial factors, general medical illness, psychiatric disorders, and psychotropic and nonpsychiatric medications. It is especially prevalent among patients with poor emotional health and has been strongly associated with antidepressant medications. Selective serotonin reuptake inhibitors (SSRIs) in particular have demonstrated a higher incidence of sexual dysfunction than other antidepressants that work through different mechanisms of action. Further supporting the relationship between sexual dysfunction and antidepressant mechanism of action, data from a number of studies indicate that bupropion, nefazodone, and mirtazapine alleviate symptoms of sexual dysfunction and are as effective as SSRIs at controlling depressive symptoms. Although a number of strategies besides drug substitution have been utilized to help manage antidepressant-induced sexual dysfunction, many patients remain suboptimally treated; as many as 42% of patients were found to passively wait for spontaneous remission. The addition of antidotal therapy has been proven to be among the effective management strategies for sexual dysfunction. However, due to a lack of systematic data, additional studies are warranted to further investigate these findings.

A placebo-controlled trial of bupropion SR as an antidote for selective serotonin reuptake inhibitor-induced sexual dysfunction.

OBJECTIVE: This study reports the results of a placebo-controlled, double-blind comparison of bupropion sustained release (SR) as an antidote for sexual dysfunction versus placebo in 42 patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. Exploratory analyses of the association of testosterone and sexual functioning in women in the study were also performed. METHOD: Patients with DSM-IV major depression who experienced a therapeutic response to any SSRI and were experiencing medication-induced global or phase-specific sexual dysfunction, as measured by the Changes in Sexual Functioning Questionnaire (CSFQ), were randomly assigned to receive either bupropion SR 150 mg b.i.d. or placebo for 4 weeks in addition to the SSRI. Total testosterone levels were assessed at baseline and week 4. RESULTS: The difference in global sexual functioning, based on the total CSFQ score, was not statistically significant between the 2 groups at week 4, nor were differences in orgasm, desire/ interest as measured by sexual thoughts, or self-reported arousal. There was a statistically significant difference between the 2 groups at week 4 in desire as measured by self-report feelings of desire and frequency of sexual activity. Desire/ frequency showed a significantly greater improvement among those patients receiving bupropion SR compared with placebo (Wilk's F = 5.47, df = 1, p =.024). Frequency was significantly correlated to total testosterone level at baseline (r = 0.36, p =.027) and at week 4 (r = 0.41, p =.025). CONCLUSIONS: Bupropion SR, as an effective antidote to SSRI-induced sexual dysfunction, produced an increase in desire to engage in sexual activity and frequency of engaging in sexual activity compared with placebo. A larger study is needed to further investigate this finding.

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.

Chronic episodic disorders in women.

Chronic episodic disorders, such as depressive disorders, IBS, migraine, and FMS, have important commonalities, including cormorbidities, an absence of classic anatomic pathology in the tissues, a lack of objective findings on physical examination, and a lack of abnormal findings by routine laboratory and radiologic tests. These CED are more prevalent in women (perhaps due to changes in estrogen levels), are generally worsened by stress (with resultant hyperactivity of the HPA axis), and often improve with aerobic exercise and common classes of medications affecting serotonin function, such as antidepressants. Thus, an increased understanding of the CED may result in improved treatment and functioning of many patients.