bremelanotide and flibanserin

The US Food and Drug Administration (FDA) has approved two drugs for 'hypoactive sexual desire disorder' in women, flibanserin (Addyi) in 2015 and bremelanotide (Vyleesi) in 2019. In this paper we examine the outcome measures and clinical trial data upon which regulatory approval was based. In clinical trials, flibanserin led to an average of only one additional enjoyable sexual experience every two months, bremelanotide to none. Trials for both drugs feature shifts in primary outcomes and a contested indication. A politicised industry-sponsored advocacy campaign and conflicted patient and expert testimony likely influenced flibanserin's approval at its third attempt. Bremelanotide, with even weaker efficacy, capitalised on the regulatory precedent set by the approval of flibanserin. Reconsideration of regulatory decisions to approve these drugs is in order, as well as a broader examination of how future regulatory decisions can better address conflicts of interest and clinically meaningful benefit.

Topics: alpha-MSH; Benzimidazoles; Female; Humans; Libido; Peptides, Cyclic

Regarding hypoactive sexual desire disorder (HSDD) in women, some reviewers judge the effect size small for medications vs placebo, but substantial for cognitive behavior therapy (CBT) or mindfulness meditation training (MMT) vs wait list. However, we lack comparisons of the effect sizes for the active intervention itself, for the control treatment, and for the differential between the two.. For efficacy trials of HSDD in women, compare effect sizes for medications (testosterone/testosterone transdermal system, flibanserin, and bremelanotide) and placebo vs effect sizes for psychotherapy and wait-list control.. We conducted a literature search for mean changes and SD on main measures of sexual desire and associated distress in trials of medications, CBT, or MMT. Effect size was used as it measures the magnitude of the intervention without confounding by sample size.. Cohen d was used to determine effect sizes.. For medications, mean (SD) effect size was 1.0 (0.34); for CBT and MMT, 1.0 (0.36); for placebo, 0.55 (0.16); and for wait list, 0.05 (0.26).. Recommendations of psychotherapy over medication for treatment of HSDD are premature and not supported by data on effect sizes. Active participation in treatment conveys considerable non-specific benefits. Caregivers should attend to biological and psychosocial elements, and patient preference, to optimize response.. Few clinical trials of psychotherapies were substantial in size or utilized adequate control paradigms. Medications and psychotherapies had similar, large effect sizes. Effect size of placebo was moderate. Effect size of wait-list control was very small, about one quarter that of placebo. Thus, a substantial non-specific therapeutic effect is associated with receiving placebo plus active care and evaluation. The difference in effect size between placebo and wait-list controls distorts the value of the subtraction of effect of the control paradigms to estimate intervention effectiveness. Pyke RE, Clayton AH. Effect Size in Efficacy Trials of Women With Decreased Sexual Desire. Sex Med Rev 2018;6:358-366.

Topics: alpha-MSH; Androgens; Benzimidazoles; Biomedical Research; Cognitive Behavioral Therapy; Female; Humans; Libido; Meditation; Mindfulness; Peptides, Cyclic; Placebos; Serotonin 5-HT2 Receptor Antagonists; Sexual Dysfunctions, Psychological; Testosterone

Hypoactive sexual desire disorder (HSDD) affects nearly 1 in 10 women. Thus, it is essential for pharmacists and other health care providers to be comfortable when discussing a patient's sexual health to ensure appropriate triage so that the specific causes of HSDD can be identified and potential recommendations provided. HSDD is defined as the absence or deficiency of sexual interest and/or desire, leading to significant distress and interpersonal difficulties. As health care providers, pharmacists have a critical role in assessing the presence of HSDD and providing education on available treatment options. This article will review the potential causes of HSDD and low sexual desire, the screening tools available, and the significant role of health care professionals in communicating with patients about their sexual health. An overview of the importance of behavioral modifications, the current pharmacologic options being investigated, and the use of complementary and alternative therapies will also be explored. Currently, buproprion is the primary pharmacologic agent that has shown positive results in treating patients with HSDD. The use of testosterone therapy will not be addressed in this article, as this therapy is described in greater detail elsewhere.

Topics: alpha-MSH; Antidepressive Agents, Second-Generation; Benzimidazoles; Bupropion; Complementary Therapies; Female; Health Behavior; Health Communication; Humans; Peptides, Cyclic; Piperazines; Purines; Receptors, Melanocortin; Reproductive Health; Serotonin Antagonists; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: alpha-MSH; Animals; Antidepressive Agents; Arousal; Benzimidazoles; Cognitive Behavioral Therapy; Contraceptives, Oral; Dopamine; Drug Approval; Epinephrine; Female; Humans; Hypothyroidism; Libido; Male; Melanocortins; Orgasm; Peptides, Cyclic; Quality of Life; Rats; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Sex Hormone-Binding Globulin; Sexology; Sexual Behavior; Sexual Dysfunctions, Psychological; Taboo; United States; United States Food and Drug Administration; Vagina; Women's Health

Topics: alpha-MSH; Benzimidazoles; Contraceptives, Oral, Hormonal; Female; Humans; Peptides, Cyclic; Receptors, Melanocortin; Reproductive Health; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Sexual Dysfunctions, Psychological; Testosterone; Women's Health