Antidepressant-induced sexual dysfunction is a significant obstacle in the treatment of patients with mood disorders, affecting up to 50% of patients who receive pharmacological treatment. Because adequate sexual function is a vital part of a healthy life, sexual dysfunction may be so distressing, some patients will often ask to switch antidepressants or discontinue treatment, despite adequate efficacy. Unlike the phosphodiesterase inhibitors for men, there are few effective treatments for women suffering from antidepressant-induced sexual dysfunction. This study will investigate the efficacy of maca root, a natural compound, in the treatment of antidepressant-induced sexual dysfunction in women. We have recently completed an NIH funded dose finding study of maca root as a treatment for antidepressant-induced sexual dysfunction in adults. More than 75% of our subjects were women. Seven subjects completed the study, and 16 (9 on 3.0g/d and 7 on 1.5g/d maca) met criteria for intent-to-treat (ITT) analysis. For all ITT subjects, maca treatment resulted in significant improvement in mean Arizona Sexual Experience Scale (ASEX) (from 23.9+4.1 to 18.0+5.5; z=- 2.80, p=0.005), and in the MGH Sexual Function Questionnaire (MGH) scores (from 23.8+4.4 to 17.9+5.9; z=-2.27, p=0.023). ITT subjects on 3.0g/d maca had a significant improvement in ASEX (from 22.8+3.8 to 16.8+6.3; z=-2.20, p=0.028) and in MGH scores (from 24.1+1.9 to 17.0+6.1; z=- 2.21, p=0.028), but subjects on 1.5g/d maca did not. Dosing group analysis showed a statistically significant improvement only in the MGH libido item for the 3.0g/d maca group (from 4.8+1.0 to 3.0+1.4; z=-2.23, p=0.026). Maca was well tolerated, with few complaints of adverse effects. We now are proposing a follow-up to the original pilot study in the form of a single-center, double- blind, randomized placebo-controlled study evaluating the efficacy of maca root in the treatment of adults with antidepressant-induced sexual dysfunction. The study will enroll 80 female outpatients with antidepressant-induced sexual dysfunction (AISD) over 40 months. Subjects will be treated with either 3000 mg/day of maca root or placebo for 12 weeks. The primary goal of our study is to determine whether maca root is more effective than placebo in reducing sexual dysfunction caused by antidepressants. As an ancillary investigation into potential mechanisms of action of maca, additional analyses will be carried out on the following: serum testosterone levels, estrogen, progesterone, and prolactin at baseline and end of the study period. If effective, maca root would be a major contribution to the pharmacopoeia available for the treatment of antidepressant-induced sexual dysfunction. The proposed study will be a randomized, double-blind placebo-controlled trial designed to investigate the efficacy of maca root in the treatment of antidepressant-induced sexual dysfunction in women. ? ? ?