Flibanserin In Women Research Articles

(017) FLIBANSERIN IMPROVES LIBIDO AND SEXUAL SATISFACTION IN WOMEN WITH BREAST CANCER ON ENDOCRINE THERAPY

Abstract Introduction Decreased libido is a distressful symptom during and after cancer treatment. This is the first prospective longitudinal study that investigates the use of flibanserin to treat decreased libido in breast cancer patients on endocrine therapy. Objective This study evaluates the efficacy of flibanserin as measured by change in desire, sexual function, and distress from sexual dysfunction. These outcomes are measured using the following validated instruments: Female Sexual Function Index (FSFI) both desire and total scores, Patient-reported Outcomes Measurement Information System Sexual Function Instrument (PROMIS-SF) and patient distress via FSDS-R. Methods Forty-three women with stage 0-III ER+ breast cancer on endocrine therapy for at least 3 months who reported HSDD as defined by the DSM-IV and ISSWH consensus paper were enrolled on an IRB-approved prospective, longitudinal trial from both an academic center and an alliance community site. All patients took flibanserin 100mg nightly for 24 to 36 weeks. Patients were monitored closely for 52 weeks for adverse events, with medical exams and questionnaires at baseline, week 4, 8, 16, 24, 52 with optional week 36 appointments. Given the small sample size, descriptive, graphical, and nonparametric paired tests for pairwise comparisons of a measure were performed. Results Participants reported improved libido and sexual satisfaction as demonstrated by both the PROMIS-SF and FSFI data (see Table 1). 35/43 (83.3%) patients completed the FSFI and 25/43 (58.1%) completed the PROMIS-SF. The mean overall total FSFI score increased from 11 at baseline, to 17 at week 8 and 24 at week 36. The PROMIS data for interest in sexual activity improved from a baseline mean score of 43 to 51 at 8 weeks, to 54 at 24 weeks and 55 at 36 weeks. Similarly, the FSFI data in the domains of desire and arousal improved respectively from 1.90 and 1.56 at baseline to 3.03 and 3.05 at 8 weeks, 3.30 and 3.17 at week 16 and 3.53 and 4.01 at week 36. Satisfaction with sex life also improved from PROMIS baseline of 46 to 49 at week 8 and 55 at week 36. FSFI data for the domain of satisfaction indicate parallel trends with a baseline score of 2.36, increasing to 3.15 at week 8 and 4.45 at week 36. Furthermore, vaginal discomfort scores improved on both the PROMIS and FSFI. FSFI data on lubrication also showed improvement with a baseline mean score of 1.85 increasing to 2.84 by week 8, 3.24 at week 24 and 4.01 at week 36. However, the PROMIS suggests a decrease in lubrication from baseline to week 8. Patient distress also decreased throughout the study as measured on the FSDS-R and distress thermometer. There were no severe adverse events. The most common adverse events were nausea, somnolence and dizziness. Conclusions Flibanserin improves libido and overall sexual function as measured by the PROMIS-SF and FSFI in breast cancer patients on endocrine therapy. The exciting data from this pilot study is currently informing a larger randomized placebo-controlled study evaluating the efficacy of flibanserin in women with breast cancer. Disclosure Yes, this is sponsored by industry/sponsor: Sprout Pharmaceuticals Clarification: Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Ms. Medicine, NanOlogy LLC, Paxman Cooling Ltd, Procter and Gamble, Rejoy, Revision Skincare, Sermonix, Shook, Hardy and Bacon, Spectrum Pharmaceuticals, Sprout Pharmaceuticals, TerSera.

Effect of flibanserin on libido in women with breast cancer on adjuvant endocrine therapy.

12015 Background: Breast cancer and its treatment can cause decreased libido. This study evaluates the use of Flibanserin in women with breast cancer on endocrine therapy who are experiencing decreased libido. It is the first study evaluating Flibanserin for medically induced decreased libido. Methods: 37 women (mean age of 49) with stage 0-III ER+ breast cancer on endocrine therapy for at least three months were enrolled on a longitudinal IRB-approved trial from both an academic center and an alliance community site. All patients met criteria for the diagnosis of HSDD as defined by the DSM-IV and ISSWSH consensus paper. Patients took Flibanserin 100mg at bedtime for 24 weeks and were followed for 52 weeks. Patients were monitored closely with medical exams and questionnaires at baseline, weeks 4, 8, 16, 24 and 52. Feasibility and efficacy of Flibanserin was measured by patient reported validated instruments such as Female Sexual Function Index (FSFI), Pittsburg Sleep Quality Index (PSQI), PROMIS, and EQ5D. Results: A statistically significant improvement in the sexual domains of desire, arousal, lubrication, orgasm, satisfaction, and pain were seen as measured by the FSFI while on Flibanserin, which declined after discontinuing the medication. At baseline, patients had an average libido of 1.7, which increased to 2.8 at 24 weeks and declined to 2.5 after discontinuing treatment. Sexual confidence and satisfaction at baseline were an average of 1.2 and 1.6 respectively and increased to an average of 2.5 and 2.6 after treatment. Ability to become lubricated was 1.3 at baseline and increased to 4.4 at 24 weeks. Ability to maintain lubrication and ease of lubrication both averaged 1.6 at baseline and increased to 3.4 at week 24. Ease and frequency of climax scored an average 1.4 at baseline, then increased to 2.6 and 2.9 respectively at week 24. Patients reported less pain and distress with sexual intercourse throughout the study and an increased number of sexually satisfying events. At baseline, the average score for overall state of health was 78/100. At 24 weeks, the average score increased to 93 and declined to 82 at week 52 (after medication was discontinued). Patients slept an average of 6.7 hours per night at baseline, which increased to 7.7 hours on Flibanserin and decreased to 5.5 hours after discontinuing the medication. Conclusions: Our study found statistically significant improvement in the sexual domains of desire, arousal, lubrication, orgasm, satisfaction, and pain as measured by the FSFI from baseline to week 24 while on Flibanserin. It also showed improved overall health-related quality of life and sleep. Flibanserin is an effective treatment option for women with breast cancer. A larger randomized placebo-controlled study is still needed to further evaluate Flibanserin in women with breast cancer and medically induced decreased libido. Clinical trial information: NCT03707340 .

Flibanserin Improves Libido In Women with Breast Cancer

ABSTRACT Introduction Sexual dysfunction is reported during and after breast cancer treatment and causes a substantial distress on women. Breast cancer and its treatment can cause decreased libido and there are currently no FDA approved medications for the treatment of disease and/or medication induced hyposexual desire disorder (HSDD). This study evaluates the use of flibanserin in breast cancer patients on endocrine therapy who are experiencing decreased libido. Objective The primary endpoint of this study is to evaluate the feasibility of flibanserin for 24 weeks in women with breast cancer on endocrine therapy. Secondary endpoints include efficacy of flibanserin as measured by the number of satisfying sexual events (SSE) per month, change in desire, change in sexual function, QoL and distress from sexual function. These outcomes are measured using a pill diary and these validated instruments: Female Sexual Function Index (FSFI) both desire and total scores, Female Sexual Distress Scale (FSDS-R), and Patient-reported Outcomes Measurement Information System Sexual Function Instrument (PROMIS-SF). Methods Twenty women with stage 0-III ER+ breast cancer on endocrine therapy for at least three months were enrolled from both an academic center and an alliance community site on a prospective, longitudinal pilot IRB-approved trial to evaluate the feasibility and efficacy of flibanserin in women with breast cancer on endocrine therapy. All patients met criteria for the diagnosis of HSDD as defined by the DSM-IV and ISSWSH consensus paper. Patients took flibanserin 100mg po at bedtime for 24 weeks and were followed for 52 weeks. Patients were monitored closely with medical exams including vital signs and completed questionnaires at baseline, weeks 4, 8, 16, 24 and 52. Given the small sample size, descriptive, graphical, and nonparametric paired tests for pairwise comparisons of a measure were performed. Results This study met its pre-defined feasibility end point. We found more than 70% of the study patients were able to complete 24 weeks of flibanserin therapy and took greater than 80% of planned doses of flibanserin as documented in their medication diary. Three patients dropped out of the study within 14 days of starting the medication due to adverse side effects. Our study also found patients subjectively reported improved libido through PROs and SSEs. The baseline mean FSFI total score was 13.3 with a desire score of 1.96 and improved to a total score of 19.4 and desire score of 3.3 by 8 weeks on flibanserin. All study participants except one reported 0 sexually satisfying events per month at baseline and this increased to 2.2 per month after 8 weeks of treatment. Patient distress also decreased from 32 to 25 on the FSDS-R and 3.33 to 2.86 on the distress thermometer at 8 weeks. Conclusions It is feasible for women with breast cancer on endocrine therapy with HSDD to take flibanserin for 24 weeks. The majority of women reported efficacy from the medication with increased libido as measured by the FSFI, increased SSEs and decreased distress. Flibanserin improved patients’ overall sexual functioning. A larger randomized placebo-controlled study is still needed to further evaluate flibanserin in women with breast cancer. Disclosure Yes, this is sponsored by industry/sponsor: The study is funded by a research grant through Sprout Pharmaceuticals Inc Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Consulting and Advisory Boards for NanOlogy, Spectrum Pharmaceuticals Inc, Sermonix Pharmaceuticals LLC, Procter & Gamble and Paxman Coolers Limited

144 Safety of Flibanserin in Women With Hypoactive Sexual Desire Disorder Taking Antidepressant Medications

Flibanserin is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the safety of flibanserin in women taking antidepressant medications. To evaluate the safety of flibanserin in women with acquired, generalized HSDD who reported the use of antidepressant medications that increase serotonergic activity during Phase 3 clinical trials. Data from 8 randomized, double-blind, placebo-controlled studies of flibanserin in HSDD (premenopausal women, protocol violators from 5 studies and patients treated for depression in 1 study; postmenopausal women, protocol violators from 2 studies) were pooled for patients receiving flibanserin 100 mg at bedtime or placebo. This analysis evaluated patients taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) at study baseline. The analysis population included 2379 flibanserin-treated (SSRI/SNRI users, n=131) and 2690 placebo-treated (SSRI/SNRI users, n=91) patients. Incidence of adverse events (AEs) in flibanserin-treated patients was 73.3% of SSRI/SNRI users and 65.4% of nonusers; incidence in placebo-treated patients was 79.1% and 54.9%, respectively. Serious AEs in SSRI/SNRI users vs nonusers occurred in 1.5% vs 1.1% of flibanserin-treated patients, respectively, and 0.0% vs 0.7% of placebo-treated patients, respectively. AEs led to treatment discontinuation in 15.3% of SSRI/SNRI users and 11.2% of nonusers who received flibanserin, and 18.7% of users and 5.3% of nonusers who received placebo. The most common AEs in flibanserin-treated patients (overall incidence ≥10%) were dizziness (6.9% of SSRI/SNRI users vs 10.5% of nonusers) and somnolence (6.1% vs 10.4%, respectively).

Safety of Flibanserin in Women With Hypoactive Sexual Desire Disorder Taking Antidepressant Medications [1D

INTRODUCTION: Flibanserin is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the safety of flibanserin in women taking antidepressant medications. METHODS: Data from 8 randomized, double-blind, placebo-controlled studies of flibanserin in HSDD (premenopausal women, protocol violators from 5 studies and patients treated for depression in 1 study; postmenopausal women, protocol violators from 2 studies) were pooled for patients receiving flibanserin 100 mg qhs or placebo. This analysis evaluated patients taking a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) at study baseline. RESULTS: The analysis population included 2379 flibanserin-treated (SSRI/SNRI users, n=131) and 2690 placebo-treated (SSRI/SNRI users, n=91) patients. Incidence of adverse events (AEs) in flibanserin-treated patients was 73.3% of SSRI/SNRI users and 65.4% of nonusers; incidence in placebo-treated patients was 79.1% and 54.9%, respectively. Serious AEs in SSRI/SNRI users vs nonusers occurred in 1.5% vs 1.1% of flibanserin-treated patients, respectively, and 0.0% vs 0.7% of placebo-treated patients, respectively. AEs led to treatment discontinuation in 15.3% of SSRI/SNRI users and 11.2% of nonusers who received flibanserin, and 18.7% of users and 5.3% of nonusers who received placebo. The most common AEs in flibanserin-treated patients (overall incidence ≥10%) were dizziness (6.9% of SSRI/SNRI users vs 10.5% of nonusers) and somnolence (6.1% vs 10.4%, respectively). CONCLUSION: In this post hoc analysis of pre- and postmenopausal women with HSDD, SSRI/SNRI use did not appear to change the AE profile of flibanserin. Concomitant use of flibanserin with moderate/strong CYP3A4 inhibitors (eg, fluvoxamine) is contraindicated.

Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study

BackgroundDepression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression. AimTo evaluate the safety of flibanserin in women treated for depression with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. MethodsIn this double-blinded, randomized, placebo-controlled trial, women with remitted or mild depression treated with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors who were not postmenopausal and were experiencing symptoms of hypoactive sexual desire disorder (ie, decreased sexual desire and related distress) received flibanserin 50 mg at bedtime (qhs) for 2 weeks and up-titrated to 100 mg qhs, flibanserin 100 mg qhs for the entire treatment period, or placebo for up to 12 weeks. OutcomesSafety assessment included adverse events and symptoms of depression and anxiety. Results73 patients were randomly assigned to flibanserin (both dose groups combined) and 38 to placebo. The sponsor terminated the study early at discontinuation of the development of flibanserin. Treatment duration was at least 8 weeks for 84.9% and 94.7% of patients in the flibanserin and placebo groups, respectively. The most common adverse events (incidence ≥ 2% in the flibanserin group and higher than that in the placebo group) included dry mouth (5.5% for flibanserin vs 2.6% for placebo), insomnia (5.5% vs 2.6%), back pain (4.1% vs 2.6%), and dizziness (4.1% vs 0.0%). There were no serious adverse events and no instances of suicidal ideation or behavior. The proportions of patients with symptom worsening in the flibanserin and placebo groups, respectively, were 6.9% and 21.6% for depression and 1.4% and 2.7% for anxiety. Remission of depression at study end point, as measured by the Quick Inventory of Depressive Symptomatology–Self Report, was experienced by 19.4% of flibanserin-treated patients and 10.8% of patients receiving placebo; remission of anxiety based on the Beck Anxiety Inventory was noted in 16.4% and 2.7% of patients, respectively. Clinical ImplicationsThe results of this study support the safety of flibanserin in premenopausal women being treated with a serotonergic antidepressant. No increased risks were observed when adding flibanserin to a stable selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor treatment regimen. Strengths and LimitationsThis was a well-designed, randomized, placebo-controlled trial. The primary limitation was the early study discontinuation by the sponsor, which decreased the sample size and duration of treatment. ConclusionIn this small trial, flibanserin 100 mg qhs was generally safe and well tolerated in premenopausal women with mild or remitted depression taking a serotonergic antidepressant.Clayton AH, Croft HA, Yuan J, et al. Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study. J Sex Med 2018;15:43–51.

Systematic Review and Meta-analysis of Flibanserin's Effects and Adverse Events in Women with Hypoactive Sexual Desire Disorder.

The efficacy and safety of flibanserin in the treatment of Hypoactive Sexual Desire Disorder (HSDD) is controversial. We reviewed existing evidence on the efficacy and safety of flibanserin in treating HSDD, and performed a meta-analysis of reported effects. Literature search was performed in PubMed, Scopus, and Cochrane library to find all trials on the efficacy of flibanserin in HSDD. Meta-analysis was performed using fixed- and random-effects models. Egger's test and "trim and fill" methods were used for the assessment of publication bias and imputation of potentially missing studies, respectively. Among 105 studies that were initially found, only ten related documents (six published and four nonpublished studies) were included in the final analysis, comprising 8345 subjects (6113 and 2232 subjects in the flibanserin and placebo groups, respectively). Incomplete outcome data bias was probable in the included studies. Most studies had an acceptable validity and quality. There was no significant difference between flibanserin and placebo groups in most of the HSDD-assessed indices. Our results showed that although SSE, DSDS, FSFID and FSFI are significantly improved with flibanserin, this change did not reach statistical significance compared with placebo. For FSDSR-item 13 score and FSDSR total score, no significant difference was observed between flibanserin and placebo. The most common side effect of flibanserin was somnolence. The most common causes of heterogeneity were black ethnicity, duration of therapy, age of participants and duration of marital relationship. the efficacy of flibanserin in women with HSDD was not found to be significantly different compared with placebo. Additional trials are required to clarify the efficacy of flibanserin for the treatment of HSDD.

Efficacy and Safety of Flibanserin in Women with Hypoactive Sexual Desire Disorder: A Systematic Review and Meta-Analysis.

Flibanserin, is a postsynaptic agonist of serotonin receptor 1A and an antagonist of serotonin receptor 2A, has been shown to increase sexual desire and reduce distress in women with hypoactive sexual desire disorder (HSDD). We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in women with HSDD. A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of flibanserin for the treatment of HSDD. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Four publications involving a total of 3,414 patients were used in the analysis, including four randomized controlled trials that compared flibanserin with placebo. For the comparison of flibanserin with placebo, primary efficacy endpoints: satisfying sexual events (the standardized mean difference [SMD] = 0.59, 95% confidence interval [CI] = 0.37-0.80, P < 0.00001); sexual desire score (the SMD = 1.91, 95% CI = 0.21 to 3.60, P = 0.03) and Female Sexual Function Index (FSFI) desire domain score (the SMD = 0.32, 95% CI = 0.19-0.46, P < 0.00001) and key secondary efficacy endpoints: FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, FSDS-R Item 13 score, Patient's Global Impression of Improvement score and Patient Benefit Evaluation indicated that flibanserin was more effective than the placebo. Safety assessments included the proportion of women who experienced an adverse event (odds ratio = 1.54, 95% CI = .34 to 1.76, P < 0.00001), nervous system disorders and fatigue indicated that flibanserin was well tolerated. This meta-analysis indicates that flibanserin to be an effective and safe treatment for HSDD in women.

Efficacy of Flibanserin in Women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA Trial

Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. The aim of this study was to assess the efficacy and safety of the 5-HT1A agonist/5-HT2A antagonist flibanserin in premenopausal women with HSDD. This was a randomized, placebo-controlled trial in which premenopausal women with HSDD (mean age: 36.6 years) were treated with flibanserin 100 mg once daily at bedtime (qhs) (n = 542) or placebo (n = 545) for 24 weeks. Coprimary end points were the change from baseline to study end in Female Sexual Function Index (FSFI) desire domain score and in number of satisfying sexual events (SSE) over 28 days. Secondary end points included the change from baseline in FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, and FSDS-R Item 13 score. Compared with placebo, flibanserin led to increases in mean (standard deviation) SSE of 2.5 (4.6) vs. 1.5 (4.5), mean (standard error [SE]) FSFI desire domain score of 1.0 (0.1) vs. 0.7 (0.1), and mean (SE) FSFI total score of 5.3 (0.3) vs. 3.5 (0.3); and decreases in mean (SE) FSDS-R Item 13 score of -1.0 (0.1) vs. -0.7 (0.1) and mean (SE) FSDS-R total score of -9.4 (0.6) vs. -6.1 (0.6); all P ≤ 0.0001. The most frequently reported adverse events in the flibanserin group were somnolence, dizziness, and nausea, with adverse events leading to discontinuation in 9.6% of women receiving flibanserin vs. 3.7% on placebo. In premenopausal women with HSDD, flibanserin 100 mg qhs resulted in significant improvements in the number of SSE and sexual desire (FSFI desire domain score) vs. placebo. Flibanserin was associated with significant reductions in distress associated with sexual dysfunction (FSDS-R total score) and distress associated with low sexual desire (FSDS-R Item 13) vs. placebo. There were no significant safety concerns associated with the use of flibanserin for 24 weeks.