FDA Approved Treatments for HSDD
At the present time, Addyi (flibanserin) and Vyleesi (bremelanotide) are the only two FDA approved medications for premenopausal women with HSDD. Both medications are non-hormonal and they are prescribed off-label to post menopausal women.
Flibanserin was originally developed by Boehringer Ingelheim in 1996 as an antidepressant, but it did not demonstrate significant efficacy for major depressive disorder in Phase 2 clinical trials. Interestingly, flibanserin was found to have a positive effect on sexual desire and in one study, 70% of women taking flibanserin reported improvements in sexual functioning compared to 30% of women who took placebo. Flibanserin was later acquired by Sprout Pharmaceuticals and in August 2015 it was FDA approved in the US under the trade name Addyi (flibanserin). Addyi, also known as the “pink pill” has been compared to Viagra (sildenafil) for men, but the two medications are very different. Addyi is non-hormonal and it works on the brain to restore balance to key neurotransmitters that are responsible for sexual desire. More specifically, it is thought to have prosexual effects by working as a serotonin 5HT-1A agonist and 5HT-2A antagonist while increasing dopamine and norepinephrine levels in the brain. Addyi works similar to an antidepressant and that is why women often report improvements in mood. It also helps facilitate sleep and that is why it is dosed at bedtime. In clinical trials, pre and postmenopausal women lost weight after taking flibanserin for 24 weeks and they maintained weight loss after 18 months of treatment: 21% of premenopausal women experienced a mean weight loss of 3.1 pounds in the flibanserin group versus 0.2 pounds in the placebo group and about 25% of postmenopausal women experienced a mean weight loss of 4 pounds compared to 0.2 pounds in the placebo group. Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause negative sexual side effects such as decreased libido and delayed response or inability to orgasm. Addyi has been used off-label to treat antidepressant-induced sexual dysfunction and it has also been shown to be safe when taken with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Addyi was found to be a safe, effective treatment in postmenopausal women, but it is not currently FDA approved in this population and therefore is considered an off-label treatment. Addyi is currently being studied in breast cancer survivors with HSDD and will soon be studied in men with HSDD.
Addyi and Alcohol
The FDA required an alcohol challenge study using a “worst case scenario” prior to the drug’s approval in 2015 and there were many unrealistic components within this small study. A total of 25 subjects were enrolled (23 of them were men, but keep in mind this drug was FDA in women). The subjects were given varying amounts of alcohol (based on weight) with Addyi or placebo on different occasions. The subjects fasted for 10 hours, were given a light breakfast, and drank grain alcohol (beer, wine, or spirits) at 10 am in 10 minutes with Addyi or placebo (also keep in mind that Addyi is dosed at bedtime because it can induce sleep). To put this in perspective, a person weighing 154 pounds was given 2 or 4 glasses of wine, beer, or 80-proof spirit and they had to drink it within 10 minutes. Ten of the subjects experienced a drop in blood pressure or syncope and no one required hospitalization. The study findings prompted a black box warning in which prescribers had to be REMS certified and patients had to agree they would abstain from alcohol while taking Addyi (keep reading because the labeling was later changed). A follow up alcohol study was conducted using a “real world scenario” and analyzed 83 women who had been taking Addyi for the past year. The amount of alcohol taken with Addyi produced a blood alcohol concentration lower than 0.08% (lower than the legal driving limit in the US) and this amount of alcohol is generally associated with feelings of improved well-being and relaxation. This realistic study did not report any cases of orthostatic hypotension or syncope and the findings were consistent with two other FDA-requested studies regarding timing/safety of alcohol intake in a real-world setting. In summary, no adverse events were noted with moderate consumption of alcohol 2-3 hours prior to taking Addyi at bedtime. It is also important to note that Addyi was approved in Canada March 2019 with no alcohol restrictions and the US FDA removed the black boxed warning regarding alcohol restrictions. Per current US FDA recommendations, women taking Addyi are now advised to abstain from alcohol two hours prior to taking Addyi at bedtime.
Addyi and Driving
The FDA also required a simulated driving study to determine if taking Addyi at bedtime would result in unsafe driving the following morning. Eighty-three women were enrolled in this study and those who took Addyi had better driving scores when compared to the placebo group.
Addyi and Pregnancy
Addyi, like most drugs, was not studied in pregnant women due to obvious ethical issues. However, in animal studies, no fetal harm was found in rats or rabbits when given up to 15 times the recommended dose in humans by weight.
Vyleesi (bremelanotide) was the second FDA approved for premenopausal women with HSDD in June 2019. This medication has been used in postmenopausal women and men which are considered off-label at this time. Vyleesi is a self-administered, on-demand subcutaneous injection in the thigh or abdomen that triggers arousal and desire in the brain by working as an agonist on the melanocortin 4 receptor site in the hypothalamus. Similar to Viagra, it requires sexual cues to stimulate a sexual response in the genitals. Vyleesi should be injected 45 minutes prior to anticipated sexual activity; only the following recommendations include: one dose per 24 hours or no more than eight doses per month (in a separate study, hyperpigmentation occurred when Vyleesi was injected for 8 consecutive days). This medication should not be used if you have uncontrolled hypertension or cardiovascular disease. Vyleesi is effective up to 14 hours, so it may be effective when injected at night and again the following morning. Nausea is the most common side effect and usually resolves by the second dose; Zofran (ondansetron) can be prescribed in conjunction with Vyleesi to prevent nausea.