How does Addyi work and is it effective?

Addyi (flibanserin) works by balancing the brain chemicals that may lead to lowered sex drive in some women. Studies with Addyi have shown significant improvements in satisfying sexual events, sexual desire and ability to lower distress in premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).

• Addyi is a non-hormonal, multifunctional serotonin agonist antagonist (MSAA).
• Addyi appears to correct an imbalance of the neurotransmitters (brain chemicals) dopamine and norepinephrine (both responsible for sexual excitement), while decreasing levels of serotonin (which can lower sex drive). As with many drugs, the exact mechanism is not known.

Addyi was first approved by the FDA in August 2015 to treat hypoactive sexual desire disorder (HSDD) in premenopausal women. That's just another way of saying it boosts sex drive (also called libido) in women who have not reached menopause. It was the first such drug approved for this use.

HSDD is the most common type of female sexual dysfunction, affecting roughly 6 million (1 out of 10) premenopausal women in the U.S. It's not used to boost sex drive in postmenopausal women or in men.

Is Addyi effective?

Yes, the effectiveness of Addyi has been shown in three 24-week, randomized, double-blind, placebo controlled studies. Results demonstrate statistically significant improvements in satisfying sexual events, sexual desire and ability to lower distress in premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD).

Addyi is a non-hormonal medicine approved by the FDA to treat ​​premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and is NOT due to:

• A co-existing medical or psychiatric (mental health) condition,
• Problems within the relationship, or
• The effects of a medication or other drug substance.

In general, you may be eligible for Addyi if you have not gone through menopause, you have not had problems with low sexual desire in the past, and you have low sexual desire no matter the type of sexual activity, the situation, or the sexual partner. Speak with your healthcare provider to learn more about this treatment and how it can help you.

Addyi is an oral tablet taken once daily at bedtime to treat HSDD. But it’s important to know that Addyi has an interaction with alcohol.

• Related: Can I take Addyi while drinking alcohol?

Addyi is not used for the treatment of HSDD in women who have gone through menopause, is not used to enhance sexual performance, and is not for use in men or children.

Study Results for Addyi

Studies have shown that in certain premenopausal women with HSDD, treatment with Addyi can increase sexual desire, increase the number of satisfying sexual events and reduce stress caused by low libido (low sex drive or desire).

Some women may see results with Addyi as early as 4 weeks, but your results may vary. Improvements include an increase in satisfying sexual events, an increase in sexual desire, and a decrease in associated distress. Not all women will experience similar improvement in their HSDD.

The efficacy of Addyi was established in three 24-week, randomized, double-blind, placebo-controlled trials in premenopausal women who had acquired, generalized hypoactive sexual desire disorder (HSDD) for at least 6 months (Studies 1, 2 and 3).

• Acquired HSDD was defined as HSDD that developed in patients who previously had no problems with sexual desire.
• Generalized HSDD was defined as HSDD that was not limited to certain types of stimulation, situations or partners.

Participants were aged 19 to 55 years (mean age 36 years) with mean duration of HSDD of 5 years and a single partner, heterosexual relationship duration of 11 years. Approximately 40% of subjects were also taking hormonal contraceptives.

Women in these trials were treated with Addyi 100 mg (1187 women) once-daily at bedtime, or placebo (1188 women). A placebo is a pill that contains no active medicine and is used in studies to help determine effectiveness of treatments.

The trials had 2 co-primary efficacy endpoints: Satisfying sexual events (SSEs) and Sexual Desire. Other endpoints included female sexual distress and clinical meaningfulness of the observed treatment effects.

Satisfying Sexual Events (SSEs)

Results showed that in all 3 trials, Addyi 100 mg resulted in statistically significant improvement compared to placebo in the change from baseline in monthly SSEs at Week 24.

Satisfying Sexual Events (SSEs) was defined as the change from the start of the study to Week 24 in the number of monthly SSEs, which might include sexual intercourse, oral sex, masturbation, or genital stimulation by the partner.

The median treatment difference increased the number of satisfying sexual events by 0.5 to 1 additional event per month over placebo (P<0.01 in study 1 and 2, and P<0.001 in study 3).

Sexual Desire

In Study 3, a statistically significant improvement was seen in the change from baseline (the start of the study) to Week 24 in sexual desire (using the desire domain of the Female Sexual Function Index, or FSFI Desire) co-primary endpoint, with Addyi compared to placebo.

The FSFI Desire Domain was determined via a patient questionnaire to assess how often the woman felt sexual desire or interest, and the level (degree) of sexual desire or interest over the 4 weeks of the study. Results showed the FSFI Desire treatment difference was 0.3 (0.2, 0.4 95% CI), P<0.0001, a significant effect when Addyi was compared to placebo.

In Study 1 and 2, there were no statistically significant differences between Addyi and placebo for the eDiary sexual desire endpoint (change in baseline to Week 24). However, the FSFI Desire Domain findings were found to be consistent across all three trials, and were used as secondary endpoints in Study 1 and 2 (statistical endpoints were not calculated because the trial failed on the eDiary Desire co-primary efficacy endpoint).

Female Sexual Distress

All 3 trials had a secondary endpoint that measured bother (a component of distress) related to sexual desire using Question 13 of the Female Sexual Distress Scale-Revised (FSDS-R).

• This question is “How often did you feel: Bothered by low sexual desire?” Patients assessed their sexual distress over a 7-day recall period and responded on a scale of 0 (never) to 4 (always).
• In Study 3, the results showed a statistically significant effect (-0.3 [-0.4, -0.1), p=0.0001 when Addy was compared to placebo for FSDS-R.
• The secondary endpoint that assessed distress using Question 13 of the FSDS-R was found to be consistent across all three trials, but statistical endpoints were not calculated for studies 1 and 2.

Clinical Meaningfulness

Additional analyses were conducted to help define the clinical meaningfulness of the observed treatment effects. The Patient's Global Impression of Improvement (PGI-I) defined responders for each efficacy endpoint by looking at the percent change in symptoms from baseline (start of study) to end of treatment.

The first analysis considered responders to be those who reported being much improved or very much improved.

• Sexually Satisfying Events (SSEs) - The absolute difference in the percentage of responders with Addyi and the percentage of responders with placebo across the three trials was 8 to 9% for SSEs (29% to 39% for Addyi; 21% to 31% for placebo).
• Female Sexual Function Index (FSFI) desire domain - The absolute difference in the percentage of responders was 10% to 13% for FSFI desire domain (43% to 48% for Addyi; 31% to 38% for placebo).
• Female Sexual Distress Scale-Revised (FSDS-R) Question 13: The absolute difference in the percentage of responders was 7% to 13% for FSDS-R Question 13 (21% to 34% for Addyi; 14% to 25% for placebo).

The second analysis considered responders to be those who reported being at least minimally improved.

• Sexually Satisfying Events (SSEs) - The absolute difference in the percentage of responders with Addyi and the percentage of responders with placebo across the three trials was 10-15% for SSEs (44-48% for ADDYI; 33-36% for placebo)
• Female Sexual Function Index (FSFI) desire domain - The absolute difference in the percentage of responders was 12% to 13% for FSFI desire domain (43% to 51% for Addyi; 31% to 39% for placebo).
• Female Sexual Distress Scale-Revised (FSDS-R) Question 13: The absolute difference in the percentage of responders was 9% to 12% for FSDS-R Question 13 (50% to 60% for Addyi; 41% to 48% for placebo).

Other studies, including a large meta-analysis from Kamrul-Hasan et al, and a post-hoc, pooled analysis of pivotal studies (VIOLET, DAISY, and BEGONIA) from Simon, et al have shown that flibanserin (Addyi) was superior to placebo in increasing the number of sexually satisfying events (SSEs), improving sexual desire scores, and lowering sexual distress in premenopausal women with HSDD.

A study in JAMA Internal Medicine found that treatment with Addyi, on average, resulted in one-half additional satisfying sexual event per month but may significantly increase the risk of some troublesome side effects, like dizziness, somnolence (drowsiness), nausea and fatigue.

Prior to treatment, women must be warned of the risk of low blood pressure, fainting, drowsiness and dizziness with this medicine, when used alone or when combined with alcohol or certain other medications. Learn more about side effects here.

How fast does Addyi work?

You may notice improvement in your HSDD symptoms, like sexual desire, an increase in satisfying sexual events and a decrease in stress associated with HSDD within 4 weeks of starting treatment.

Tell your doctor if your symptoms of HSDD have not improved after you have taken your treatment for 8 weeks.

What are the common safety concerns with Addyi?

Common side effects with Addyi (in at least 2% of patients in studies) include:

• Dizziness
• Sleepiness
• Nausea
• Fatigue
• Trouble sleeping (insomnia)
• Dry mouth

Addyi is taken as an oral tablet once daily at bedtime, but there is a risk of severe low blood pressure and fainting with this medicine, when used alone or when combined with alcohol or some other medicines.

Do not drink alcohol close to the time you take your Addyi dose because this increases your risk of severe low blood pressure and fainting (loss of consciousness). Wait at least 2 hours after drinking 1 or 2 standard alcoholic drinks before taking Addyi at bedtime. Skip your Addyi dose if you have consumed 3 or more standard alcoholic drinks that evening.

Examples of 1 standard alcoholic drink include:

• one 12-ounce regular beer (5% alcohol)
• 5 ounces of wine (12% alcohol)
• 1.5 ounces of distilled spirits or shot (40% alcohol)

After you have taken your Addyi at bedtime do not drink alcohol until the following day.

Do not drive, operate machinery, or do anything that requires clear thinking and full alertness until at least 6 hours after you take Addyi and until you know how this medicine affects you.

Do not take Addyi if you have liver problems. This may also increase your risk of severe low blood pressure and fainting (loss of consciousness). If you are not sure if you have liver problems, talk to your doctor.

Do not take or start taking any prescription medicines, over-the-counter (OTC) medicines, vitamin or herbal supplements while taking Addyi until you have talked with your doctor. These combinations may not be safe and increase your risk of severe low blood pressure and fainting.

Do not take Addyi if you take drugs known as moderate or strong CYP3A4 inhibitors. If you are not sure, ask your doctor or pharmacist. Taking these drugs together can increase the blood levels of Addyi in your body and could increase your risk of low blood pressure or fainting.

If you take Addyi and you feel lightheaded or dizzy, lie down right away. Get emergency medical help, or ask someone to get emergency medical help for you, if the symptoms do not go away or if you feel like you could faint (lose consciousness). Tell your doctor as soon as possible if you faint (lose consciousness).

This is not all the information you need to know about Addyi (flibanserin) for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.