Drug Classes for Treating Hypoactive Sexual Desire Disorder (HSDD)
The two FDA-approved drug classes for treating hypoactive sexual desire disorder (HSDD) are melanocortin receptor agonists (bremelanotide) and serotonin mixed agonist/antagonists (flibanserin). 1, 2, 3
First-Line FDA-Approved Medications
- Melanocortin receptor agonists: Bremelanotide (Vyleesi) is FDA-approved for premenopausal women with acquired, generalized HSDD and works by activating melanocortin receptors in the brain, particularly subtype 4 (MC4R) 2, 4
- Serotonin mixed agonist/antagonists: Flibanserin (Addyi) is FDA-approved for premenopausal women with HSDD and is taken daily at bedtime 1, 3
Mechanism of Action
- Melanocortin receptor agonists (bremelanotide) activate presynaptic MC4Rs on neurons in the medial preoptic area of the hypothalamus, leading to increased release of dopamine, an excitatory neurotransmitter that increases sexual desire 4
- Serotonin mixed agonist/antagonists (flibanserin) work by modulating brain neurotransmitters, affecting the balance between excitatory and inhibitory pathways involved in sexual desire 3, 5
Off-Label Treatment Options
- Antidepressants: Bupropion may be considered off-label for HSDD despite limited safety and efficacy data 1, 5
- Anxiolytics: Buspirone is another off-label option for premenopausal women with HSDD 1, 6
- Androgens: Testosterone may be discussed for women with low desire, though not FDA-approved specifically for HSDD 1, 5
Administration and Dosing
- Bremelanotide is administered as a self-administered subcutaneous injection (1.75 mg) as needed, at least 45 minutes before anticipated sexual activity 2, 7
- Flibanserin is taken orally as a 100 mg tablet once daily at bedtime 1, 3
Efficacy Considerations
- Flibanserin results in approximately 1 additional satisfying sexual event every 2 months compared to placebo in premenopausal women with HSDD 1, 6
- Bremelanotide significantly improves sexual desire and reduces distress related to low sexual desire compared to placebo in clinical trials 8, 7
Important Limitations
- Neither medication is indicated for treatment of HSDD in postmenopausal women or men 2, 3
- Neither medication is indicated to enhance sexual performance in individuals without HSDD 2, 3
- Phosphodiesterase type 5 inhibitors (PDE5i) are NOT recommended for female sexual dysfunction due to contradictory results in clinical trials 1
Contraindications and Precautions
- Flibanserin has significant interactions with alcohol and moderate/strong CYP3A4 inhibitors, which can increase the risk of severe hypotension and syncope 3
- Flibanserin is contraindicated in patients with liver problems 3
- Both medications should be used with caution due to their limited efficacy and potential adverse effects 6