Does Addyi (Flibanserin) Really Work?
Yes, Addyi (flibanserin) does work for premenopausal women with hypoactive sexual desire disorder (HSDD), but the effect is modest—resulting in approximately one additional satisfying sexual event every two months compared to placebo. 1, 2
Efficacy Evidence
Statistically Significant but Modest Clinical Benefits
Flibanserin 100 mg daily at bedtime produces statistically significant improvements across multiple validated measures of sexual function in premenopausal women with HSDD. 3
In pooled analysis of three pivotal trials involving 2,465 premenopausal women, flibanserin increased satisfying sexual events by an average of 0.9 additional events per month (2.1 vs 1.2 for placebo). 4
The systematic review and meta-analysis found a pooled mean difference of only 0.49 satisfying sexual events per month between flibanserin and placebo (approximately one-half additional event monthly). 2
The National Comprehensive Cancer Network and American College of Obstetricians and Gynecologists recommend flibanserin as first-line FDA-approved treatment for premenopausal women with HSDD, acknowledging its modest efficacy of approximately 1 additional satisfying sexual event every 2 months. 1
Improvements in Desire and Distress Measures
Flibanserin significantly improved Female Sexual Function Index (FSFI) desire domain scores compared to placebo (mean difference 0.27-0.9 points depending on the study). 4, 2, 5
Distress related to low sexual desire (measured by FSDS-R Item 13) decreased significantly more with flibanserin than placebo (-0.9 vs -0.6). 4
Between 44-47% of women receiving flibanserin considered their HSDD to have improved versus 30% on placebo. 6
Important Safety Considerations and Limitations
Significant Adverse Event Profile
The most common adverse events are dizziness (risk ratio 4.00), somnolence (risk ratio 3.97), nausea (risk ratio 2.35), and fatigue (risk ratio 1.64) compared to placebo. 2
Discontinuation due to adverse events occurred in approximately 10% of flibanserin-treated women versus 4% on placebo. 2, 5
Critical Drug Interactions and Contraindications
Flibanserin is absolutely contraindicated with moderate or strong CYP3A4 inhibitors due to risk of severe hypotension and syncope. 7
Alcohol consumption within 2 hours of taking flibanserin significantly increases risk of severe hypotension and syncope. 7 Patients must wait at least 2 hours after consuming 1-2 standard drinks before taking the bedtime dose, or skip the dose entirely if they consumed 3 or more drinks. 7
Flibanserin is contraindicated in patients with any degree of hepatic impairment due to increased drug concentrations and risk of severe hypotension and syncope. 7
Dosing and Administration Requirements
The only approved dose is 100 mg once daily at bedtime—daytime dosing increases risks of hypotension, syncope, accidental injury, and CNS depression. 7
Discontinue flibanserin after 8 weeks if the patient reports no improvement in symptoms. 7
Population-Specific Considerations
Premenopausal Women (FDA-Approved Population)
All pivotal trials enrolled premenopausal women with a mean age of 35-37 years and mean HSDD duration of approximately 5 years. 6, 4, 5
Efficacy was generally consistent across various demographic and baseline characteristic subgroups. 4
Postmenopausal Women (Off-Label)
One trial (PLUMERIA) in postmenopausal women showed significant improvement in FSFI desire scores but failed to reach statistical significance for satisfying sexual events (the study was discontinued early by the sponsor). 8
Flibanserin is NOT FDA-approved for postmenopausal women, though the American College of Obstetricians and Gynecologists suggests it may be considered off-label. 1, 8
Cancer Survivors
Data on efficacy in cancer survivors is extremely limited, as most studies excluded this population. 1
For cancer survivors with hormone-sensitive cancers, treatment selection requires careful consideration. 1
Clinical Decision-Making Algorithm
When to Consider Flibanserin
Premenopausal women with acquired, generalized HSDD causing marked distress or interpersonal difficulty 7
After ruling out medical/psychiatric conditions, relationship problems, or medication effects as the primary cause 7
No hepatic impairment of any degree 7
Able to avoid moderate/strong CYP3A4 inhibitors 7
Willing and able to adhere to strict alcohol timing restrictions 7
When NOT to Use Flibanserin
Postmenopausal women (not FDA-approved; consider bremelanotide as alternative first-line option) 1
Any hepatic impairment 7
Concurrent use of moderate/strong CYP3A4 inhibitors 7
Patients unable to comply with alcohol restrictions 7
To enhance sexual performance (not indicated for this purpose) 7
Quality of Evidence Assessment
The overall quality of evidence for flibanserin was graded as "very low" in the most comprehensive systematic review, primarily due to concerns about clinical significance of the modest effect size and the exclusion of women with comorbidities and medication use from trials. 2
Future studies should include more diverse populations, particularly women with comorbidities, concurrent medication use, and surgical menopause. 2
Common Pitfalls to Avoid
Do not prescribe flibanserin for postmenopausal women without discussing that this is off-label use with limited supporting evidence 1, 8
Do not fail to screen for hepatic impairment before prescribing 7
Do not neglect thorough medication reconciliation to identify CYP3A4 inhibitors 7
Do not minimize the importance of alcohol timing restrictions—this is a boxed warning for severe hypotension and syncope 7
Do not continue flibanserin beyond 8 weeks without documented symptom improvement 7
Do not overlook psychological factors, relationship issues, or other treatable causes of low desire that may respond better to non-pharmacologic interventions 1