flibanserin for hypoactive sexual desire disorder

Last edited 10/2021 and last reviewed 10/2021

Flibanserin for hypoactive sexual desire disorder

Flibanserin was the first pharmacologic treatment, approved by the United States Food and Drug Administration in August 2015, for hypoactive sexual desire disorder (HSDD) in premenopausal women (1)

Hypoactive sexual desire disorder (HSDD) is defined as a persistent or recurrent deficiency (or absence) of sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty not related to a medical or psychiatric condition or the use of a substance or medication (2,3)

Flibanserin is a 5-hydroxytryptamine 1A (5-HT1A) agonist/5-HT2A antagonist that also exhibits weak to moderate antagonism at 5-HT2B, 5-HT2C, and dopamine D4 receptors (4,5)

• chemical and empirical formula are 2H-benzimidazol-2-one, 1, 3-dihydro-1-[2-[4-[3-(trifluoromethyl) phenyl]-1-piperazinyl]ethyl] and C20H21F3N4O, respectively
• acts as a full agonist at postsynaptic 5HT1A receptors and an antagonist at postsynaptic 5HT2A receptors (4)
  • exclusive binding at these receptors differentiates flibanserin from buspirone and bupropion (5)
  • this action in the prefrontal cortex causes the downstream release of dopamine and norepinephrine and reduction of serotonin, consistent with sites of abnormal neuroimaging described in patients with reduced sexual interest and desire
    • both dopamine and norepinephrine play a critical role in sexual excitation, with norepinephrine playing a stimulating role in sexual arousal and dopamine playing a role in boosting desire (6)
  • acts selectively on pyramidal neurons that excite brainstem 5HT neurons yet also selectively on pyramidal neurons that inhibit brainstem Norepinephrine and Dopamine neurons

Flibanserin

• undergoes oxidative metabolism by CYP3A4 and to a lesser extent by CYP2D6 cytochrome P450 isoenzymes
• concomitant CYP3A4 inhibitors may increase flibanserin exposure and are contraindicated
• use of flibanserin in patients who are CYP2C19 poor metabolizers results in increased flibanserin concentrations and may increase the risk of hypotension and syncope
• inhibits P-glycoprotein
  • requires increased monitoring of concentrations of drugs transported by P-glycoprotein that have a narrow therapeutic index such as digoxin and sirolimus is indicated
• should not be taken during daytime hours because this increases the risk of hypotension, somnolence, and syncope (6)

A review concluded (5):

• "..Flibanserin is a controversial drug approved for a controversial disorder amid huge controversy. While it may serve as the lamp in the light in the long search for female sexual problems, it has still a long way to go. Women taking this drug must well be educated about the adverse events associated with this drug and the possible interactions. Until further data are available, a cautious use of the drug is warranted.."

Reference:

• Gelman F, Atrio J. Flibanserin for hypoactive sexual desire disorder: place in therapy. Ther Adv Chronic Dis. 2017;8(1):16-25. doi:10.1177/2040622316679933
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text rev.Washington, DC: American Psychiatric Association; 2000.
• Goldstein I, Kim NN, Clayton AH, et al. Hypoactive sexual desire disorder: International Society for the Study of Women’s Sexual Health (ISSWSH) expert consensus panel review. Mayo Clin Proc 2017;92:114-128
• Lodise NM. Female sexual dysfunction: a focus on flibanserin. Int J Womens Health. 2017;9:757-767. Published 2017 Oct 11. doi:10.2147/IJWH.S83747
• Baid R, Agarwal R. Flibanserin: A controversial drug for female hypoactive sexual desire disorder. Ind Psychiatry J. 2018;27(1):154-157. doi:10.4103/ipj.ipj_20_16
• English C, Muhleisen A, Rey JA. Flibanserin (Addyi): The First FDA-Approved Treatment for Female Sexual Interest/Arousal Disorder in Premenopausal Women. P T. 2017;42(4):237-241.