What is the recommended treatment approach for a premenopausal woman with hypoactive sexual desire disorder (HSDD) considering Addyi (flibanserin)?

Addyi (Flibanserin) for Hypoactive Sexual Desire Disorder

Flibanserin 100 mg taken once daily at bedtime is the FDA-approved first-line pharmacological treatment for premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), though its clinical benefit is modest—approximately one additional satisfying sexual event every 2 months compared to placebo. 1, 2, 3

Patient Selection and Diagnosis

Before prescribing flibanserin, confirm the diagnosis of HSDD requires all of the following criteria 3:

• Premenopausal status (not indicated for postmenopausal women or men)
• Acquired, generalized low sexual desire causing marked distress or interpersonal difficulty
• NOT attributable to:
  • Co-existing medical or psychiatric conditions
  • Relationship problems
  • Effects of medications or other substances

Dosing and Administration

The recommended dose is 100 mg taken once daily at bedtime. 3 This bedtime-only dosing is mandatory, not optional, because daytime administration significantly increases risks of hypotension, syncope, accidental injury, and CNS depression. 3

• Patients should avoid activities requiring full alertness (driving, operating machinery) until at least 6 hours after each dose and until they understand how flibanserin affects them 3
• Discontinue treatment after 8 weeks if no improvement is observed 3

Expected Efficacy

Set realistic expectations with patients about the modest benefits 1, 2, 4:

• Approximately 0.5-1 additional satisfying sexual event per month compared to placebo
• Statistically significant but clinically modest improvements in sexual desire scores (FSFI desire domain increase of ~0.3 points) 4, 5
• Reduction in distress related to low sexual desire 6, 4
• 44-47% of women report subjective improvement versus 30% on placebo 7

Critical Safety Warnings and Contraindications

Absolute Contraindications 3:

• Moderate or strong CYP3A4 inhibitors (including common medications like fluconazole, erythromycin, grapefruit juice)
• Any degree of hepatic impairment
• Hypersensitivity to flibanserin

Alcohol Interaction - Boxed Warning 3:

• After taking flibanserin at bedtime, patients must avoid alcohol until the following day
• If consuming alcohol in the evening:
  • Wait at least 2 hours after 1-2 standard drinks before taking flibanserin
  • Skip the flibanserin dose entirely if consuming 3 or more drinks
• Combined use dramatically increases risk of severe hypotension and syncope 3

Common Adverse Effects

The most frequent adverse events (≥2% incidence) include 3, 8, 5:

• Dizziness (risk ratio 4.00 vs placebo)
• Somnolence (risk ratio 3.97 vs placebo)
• Nausea (risk ratio 2.35 vs placebo)
• Fatigue (risk ratio 1.64 vs placebo)
• Insomnia and dry mouth

Discontinuation due to adverse events occurs in approximately 10% of patients versus 4% on placebo. 8 However, serious adverse events are comparable to placebo. 5

Important Drug Interactions

Weak CYP3A4 inhibitors (including oral contraceptives) increase flibanserin exposure and adverse event incidence—monitor closely but not contraindicated. 3, 4

Strong CYP2C19 inhibitors increase flibanserin concentrations, raising risks of hypotension, syncope, and CNS depression—use with caution. 3

CYP3A4 inducers substantially reduce flibanserin concentrations—use not recommended. 3

Digoxin: Flibanserin increases digoxin concentrations; increase monitoring for digoxin toxicity. 3

Special Populations

• CYP2C19 poor metabolizers have increased flibanserin exposure with heightened risk of hypotension, syncope, and CNS depression 3
• Nursing mothers: Flibanserin is not recommended 3
• Cancer survivors: Limited data exist, but flibanserin may be considered for appropriate candidates without contraindications 1, 9

Alternative Treatment Options

If flibanserin is contraindicated, ineffective, or not tolerated 1:

• Bremelanotide (FDA-approved alternative, subcutaneous injection as needed for premenopausal women)
• Off-label bupropion (limited safety/efficacy data)
• Off-label buspirone (limited data)
• Non-pharmacological approaches: psychological counseling for anxiety/depression, relationship counseling, pelvic physical therapy, mechanical devices (vibrators, clitoral stimulators)

Common Pitfalls

• Do not prescribe PDE5 inhibitors (sildenafil, tadalafil) for female sexual dysfunction—contradictory trial results and lack of efficacy data in women 1
• Avoid "restorative or regenerative" therapies lacking FDA approval and robust clinical trial data 1
• Remember that psychological factors often significantly contribute to sexual dysfunction and should be addressed concurrently 1