PT-141 vs Addyi: Comparing Bremelanotide and Flibanserin for Low Desire

PT-141 vs Addyi at a glance

Bremelanotide (PT-141) and flibanserin are the two medicines the FDA has approved specifically for low sexual desire in women. Both treat hypoactive sexual desire disorder (HSDD): low desire that has developed over time, happens in every situation, causes real distress, and isn't better explained by another medical condition, medication or relationship problem. Beyond that, they are very different medicines.

Sources: the current Vyleesi and Addyi prescribing information. Labels change, so your clinician will check the current version.

How do PT-141 and Addyi work differently?

PT-141: on-demand, melanocortin pathway

Bremelanotide is a peptide that switches on melanocortin receptors (mainly MC4) in brain regions involved in sexual motivation. It is taken only when you expect sexual activity, so there is no daily routine. Our full guide to PT-141 for women covers how it works and its safety in more depth.

Addyi: daily, serotonin pathway

Flibanserin acts on serotonin receptors and is thought to shift the balance of brain chemicals toward excitation, but the label states that its mechanism in HSDD is not known. It is taken every night, whether or not you plan to have sex, and its effect builds over weeks rather than hours. It is taken at bedtime because taking it during the day increases the risk of low blood pressure, fainting and sleepiness.

Which works better for low desire?

No trial has compared bremelanotide and flibanserin directly, so any claim that one "works better" is a guess. What we can compare is how each did against placebo.

PT-141 trial results

In two 24-week trials of 1,267 premenopausal women, bremelanotide improved desire scores and reduced distress more than placebo, but did not meaningfully increase the number of satisfying sexual events (Kingsberg 2019). The average improvement in desire was 0.30 to 0.42 points on a 1.2 to 6.0 scale.

Addyi trial results

In the three main trials in premenopausal women, flibanserin increased the number of satisfying sexual events compared with placebo. According to the label, 44% to 48% of women on flibanserin were responders on that measure, compared with 33% to 36% on placebo, a difference of about 10 to 15 percentage points. Results for the desire measure were mixed across trials. A meta-analysis of eight studies including 5,914 women found that, on average, flibanserin added about half a satisfying sexual event per month over placebo, and that women's own ratings showed minimal improvement to no change (Jaspers 2016). The Addyi label also reports a separate trial in naturally postmenopausal women under 65 that found improvement versus placebo.

By the numbers

How each did against placebo

0.30–0.42points average desire-score gain on bremelanotide (1.2–6.0 scale)Source: Kingsberg 2019

44%–48%responders on flibanserin, vs. 33%–36% on placeboSource: Addyi label

~0.5extra satisfying sexual events a month on flibanserin over placeboSource: Jaspers 2016

Side effects: PT-141 vs Addyi

PT-141 side effects

• Nausea in 40% of women in the trials (most often after the first dose); 13% used anti-nausea medicine and 8% stopped because of it
• Flushing (about 20%), injection-site reactions (about 13%) and headache (about 11%)
• Temporary blood pressure rise after each dose, up to about 6/3 mmHg, usually gone within 12 hours
• Darkened skin patches on the face, gums or breasts in about 1%, which may not fully fade

Addyi side effects

• Dizziness and sleepiness are the most common, along with nausea, fatigue, insomnia and dry mouth
• Low blood pressure and fainting, the reason for its boxed warning
• Next-day sleepiness, so the label advises not to drive or do anything that requires alertness until at least six hours after a dose, and until you know how it affects you

In the meta-analysis, women on flibanserin were about four times as likely as those on placebo to report dizziness or sleepiness, and about twice as likely to stop treatment because of side effects.

Addyi and alcohol: what the label says now

Older articles often say you can't drink at all on Addyi. The label was updated, and the current wording is more specific:

• After one or two standard drinks, wait at least two hours before taking Addyi at bedtime.
• After three or more drinks that evening, skip that night's dose.
• After taking Addyi at bedtime, don't drink alcohol until the next day.

Which one might suit you?

These are general patterns, not a recommendation. A clinician has to look at your health history, medications and goals.

PT-141 may suit you better if you prefer to take something only when you need it, you are premenopausal, you drink alcohol socially, and your blood pressure is well controlled with no heart disease. You also need to be comfortable with an injection and with the chance of nausea.

Addyi may suit you better if you'd rather take a nightly pill than inject, you're comfortable following the alcohol timing rules, you don't take interacting medicines, and the label's age and menopause criteria fit you.

Neither may be the right first step if pain with sex, vaginal dryness, depression, a medication side effect, poor sleep or relationship strain is driving the problem. Expert guidance recommends looking for and treating those causes first or alongside any medicine (Clayton 2018). After menopause, testosterone therapy has the strongest evidence for distressing low desire; see testosterone and libido in women.

What about compounded PT-141 and combination products?

Some telehealth services prescribe compounded bremelanotide in forms other than the Vyleesi injection, such as dissolving tablets, sometimes combined with other medicines. Amie offers one: Blys™, a rapid-dissolve tablet with PT-141, oxytocin and tadalafil, taken 30 to 60 minutes before intimacy for low desire and arousal, designed with women on antidepressants in mind. Blys is compounded and not FDA-approved, its use is off-label, and it has not been tested against Vyleesi or Addyi.

Questions to bring to your appointment

• Does my low desire fit HSDD, or is something else the main driver?
• Am I premenopausal, perimenopausal or postmenopausal, and which options does that leave?
• How much alcohol do I drink, and would Addyi's timing rules be realistic for me?
• Is my blood pressure well controlled? Do I have any heart or liver conditions?
• Which of my current medicines or supplements could interact?
• How will we decide after 8 weeks whether to continue?

For an overview of every option, from lifestyle changes to prescriptions, visit our libido treatments hub.