Effects of Flibanserin on the Pharmacokinetics of a Combined Ethinylestradiol/Levonorgestrel Oral Contraceptive in Healthy Premenopausal Women: A Randomized Crossover Study

Johnson‐Agbakwu, Crista; Brown, Louise; Yuan, James; Kissling, Robert; Greenblatt, David J.

doi:10.1016/j.clinthera.2017.08.021

Cited by 11 publications

(5 citation statements)

References 39 publications

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“…Sexual dysfunction as a side effect is often attributed to monoaminergic and dopaminergic activity of antidepressants (Clayton et al, 2014). The pharmacological profile of pimavanserin may explain improvements in sexual dysfunction observed with in this study and is consistent with the hypothesis that 5‐HT 2 antagonism may improve sexual functioning (Johnson‐Agbakwu et al, 2018; Stryjer et al, 2009). The effects of pimavanserin on sexual dysfunction in this study also could be attributed to improvements in depressive symptoms.…”

Section: Discussionsupporting

confidence: 91%

“…CLARITY was a randomized, double‐blind, and placebo‐controlled study that demonstrated robust efficacy of adjunctive pimavanserin in patients with MDD and an inadequate response to treatment with an SSRI or SNRI (Fava et al, 2019). Given the fact that pimavanserin acts as a potent inverse agonist at 5‐HT 2A receptors, and to a lesser extent at 5‐HT 2C receptors (Vanover et al, 2006), and that 5‐HT 2 antagonism has been shown to be helpful in the treatment of sexual dysfunction (Johnson‐Agbakwu, Brown, Yuan, Kissling, & Greenblatt, 2018; Stryjer et al, 2009), we conducted additional analyses from CLARITY to address (a) whether adjunctive pimavanserin augments or improves sexual functioning versus placebo; (b) if this effect is accounted for by changes in depression severity; and (c) if there are baseline factors that moderate the improvement in sexual function with pimavanserin.…”

Section: Introductionmentioning

confidence: 99%

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Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

et al. 2020

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Background: Sexual dysfunction is common among patients with major depressive disorder (MDD). In the CLARITY study, the safety and efficacy of adjunctive pimavanserin, an inverse agonist at 5-HT 2A receptors, were demonstrated when added to existing treatment for MDD. This analysis provides a detailed assessment of the effects of pimavanserin on sexual function from the CLARITY study. Methods: Patients with a diagnosis of MDD in a depressive episode, inadequate response to ongoing antidepressant therapy, and a Montgomery-Åsberg Depression Rating Scale total score >20 were randomized to pimavanserin 34 mg/day or placebo added to ongoing treatment with an immediate revision of all selective serotonin or serotonin-norepinephrine for 5 weeks (Stage 1), and nonresponders (<50% improvement from baseline in Hamilton Depression Rating Scale [HAMD-17]) were re-randomized for an additional 5 week (Stage 2). Effects of pimavanserin on the Massachusetts General Hospital Sexual Functioning Index (MGH-SFI) and HAMD-17 Item 14 (sexual interest) were examined. Results: Among 203 patients (51 on pimavanserin; 152 on placebo), pimavanserin demonstrated significant improvement from baseline to Week 5 on the MGH-SFI (least square [LS]mean difference −0.634, 95% confidence interval [CI] [−0.964, −0.304]; p = .0002; effect size [ES], Cohen's d: .614). Across Stages 1 and 2, the weighted LSmean difference was −0.468 (95% CI [−0.720, −0.216]; p = .0003) for pimavanserin versus placebo. Mean changes from baseline to Week 5 for MGH-SFI Items 1, 2, 3, and 5 and HAMD Item 14 were significantly (p < .05) greater with pimavanserin versus placebo. Conclusions: Adjunctive pimavanserin improved sexual function in patients with MDD. Adding pimavanserin to ongoing treatment for MDD may be especially useful for patients experiencing sexual dysfunction. K E Y W O R D S adjunctive, major depressive disorder, pimavanserin, sexual function

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

et al. 2020

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“…This behavior causes a reduction in the serotonin level in the brain, as well as the elevation of norepinephrine neurotransmitters, which results in the improvement of sexual functioning in premenopausal women [4][5][6]. Thus, it was approved by the FDA in 2015 for the management of patients with hyposexual desire disorder (HSDD) [7]. The FDA approved a dose of 100-mg FB/day, which is rapidly absorbed after oral administration and excreted as unchanged drug in the urine [8].…”

Section: Introductionmentioning

confidence: 99%

Development and Greenness Evaluation of Spectrofluorometric Methods for Flibanserin Determination in Dosage Form and Human Urine Samples

Ahmed

Abdallah

2020

Molecules

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Green, economic and sensitive two spectrofluorometric methods were developed for the quantitation of flibanserin (FB) in different matrices, which are based on FB native fluorescence properties. The first technique depends on measuring the relative fluorescence intensity of FB directly at emission and excitation wavelengths(λem/λex) (371 nm/247 nm), while the second technique is a first derivative (D1) spectrofluorometric method, which depends on measuring the peak amplitudes at 351 nm. Linear regressions were observed in the range of 0.1–1.5 μg/mL for both methods. Moreover, both methods were efficiently extended to analyze FB in human urine, indicating the ultra-sensitivity of the methods, and linear regression was found within a range 0.05–0.7 μg/mL for both methods. Excellent selectivity of the proposed methods and good recoveries were obtained upon the analysis of FB in pharmaceutical dosage form and human urine samples without interference from matrix components with acceptable ranges, from 98.86 to 101.46% and from 98.08 to 102.37%, respectively. Greenness of the developed methods was assessed using the national environmental method index (NEMI) and Analytical Eco-scale and Green Analytical Procedure Index (GAPI). The three approaches confirmed that the developed methods are green, safe and environment-friendly.

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“…These neurotransmitters have been associated with excitatory and inhibitory responses to sexual cues implicated in HSDD [ 13 ]. Clinical trials have demonstrated that subjects experienced improved satisfying sexual events after taking flibanserin compared to that of the control group [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. Flibanserin was initially rejected for approval by the FDA in 2010 due to concerns over efficacy and safety data [ 53 , 65 ].…”

Section: Current Treatmentmentioning

confidence: 99%

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

Edinoff

Sanders

Lewis

et al. 2022

Neurology International

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Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

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Effects of Flibanserin on the Pharmacokinetics of a Combined Ethinylestradiol/Levonorgestrel Oral Contraceptive in Healthy Premenopausal Women: A Randomized Crossover Study

Cited by 11 publications

References 39 publications

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis

Development and Greenness Evaluation of Spectrofluorometric Methods for Flibanserin Determination in Dosage Form and Human Urine Samples

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

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