099 Flibanserin vs. Mini-Dose Trazodone for Female Sexual Dysfunction? A Challenge

Abstract

Hypoactive Sexual Desire Disorder (HSDD) is the most common sexual dysfunction in pre-menopausal women, but post-menopausal women and women taking antidepressants or with breast or gynecologic cancer frequently have mixed or global sexual dysfunction. Flibanserin (FLI), the only drug approved for HSDD, is not licensed for post-menopausal use or for sexual arousal, orgasm, or sexual pain. Trazodone (TRZ) is unapproved for sexual dysfunction, but small trials and receptor data suggest value for various aspects. FLI and TRZ share some pharmacologic properties, including tolerability issues (CNS depression, drowsiness, dizziness, etc). This work is to compare experimental Results of relevance to efficacy and tolerability of FLI and TRZ for treating mixed or global sexual dysfunction in women. Conduct a literature review of human brain receptor properties, animal and clinical pharmacology, and relevant clinical trials of FLI and TRZ to compare the two. Table 1 summarizes Results. The additional receptor effects of TRZ (5HT2C, alpha) might increase sexual motivation and sexual arousal and thus improve lubrication, mitigating dyspareunia. Evidence for increased brain dopamine, and thus for facilitation of orgasm, is not directly available for TRZ but is positive (in animals) for FLI, yet this may be a general property of 1A agonists including TRZ, which equaled bupropion in improving orgasm (and desire) in a small clinical study. The H1 antagonism of TRZ, which may explain its more sedative properties, becomes relevant only with doses much larger than those required for 1A, 2A, and α1 receptor occupancy. With 100 mg FLI, 2A receptor effects apparently last for about 4 hours; 1A receptor effects, for >24 hours. With extended release TRZ, both receptors should be activated for 24 hours, even after a dose as low as 12 mg.