Safety and Effectiveness Study of Maca Root to Treat Antidepressant-Induced Sexual Dysfunction

The purpose of this study is to determine whether Maca Root is effective for the treatment of
antidepressant-induced sexual dysfunction, and to further determine whether higher doses of
Maca Root powder would be more effective than lower doses in reducing the symptoms of
antidepressant-induced sexual dysfunction. An additional aim of the study is to document the
safety and tolerability of Maca Root, which could be particularly helpful in treating
antidepressant-induced sexual dysfunction in elderly and cardiac-impaired populations taking
oral nitrates who may not be eligible for treatment with the current oral phosphodiesterase
inhibitors.

Subjects will be randomized into two arms of 10 for this 12-week study. The study will be
double blind with regard to doses received. Ten subjects will receive 1500mg/day of maca for
the 12-week period and the other 10 subjects will receive 3000mg/day of maca per day for the
12-week study period. Patients will be seen every other week. There is no placebo arm.

At the final study visit, week 12, subjects will be evaluated to see if their sexual function
has returned.

After careful review of the literature we have found that there are very few studies that
have evaluated Maca Root in humans. However the one very relevant study completed by Gonzalez
and colleagues looked at doses of 1500 and 3000mg in men and found there were increased
sexual interests on both doses. Thus, since this is a dose-finding study we believe this dose
is an appropriate place to begin.

Hypotheses A:

The response rate will be higher for the high-dose maca group compared to the low-dose group;
and this response will be comparable to the 50-85% reported with sildenafil.

Hypothesis B:

There will be a statistically significant difference in the magnitude of response between the
two testing conditions, as measured by a decrease in baseline sexual dysfunction scores. The
reduction in sexual dysfunction scores will be greater in the high-dose maca group than in
the low-dose maca group.

Inclusion Criteria:

- Subjects have been taking an SSRI, venlafaxine, nefazodone, or tri/hetero cyclic
antidepressant for treatment of depression for at least 8 weeks, are currently at a
stable dose of the antidepressant for at least 4 weeks, and have been consistently
experiencing arousal dysfunction (inability to attain or maintain an adequate
lubrication/swelling response of sexual excitement until completion of sexual
activity) or orgasmic dysfunction (delayed orgasm/anorgasmia following a normal sexual
excitement phase) that interferes with sexual function for at least 4 weeks.

Subjects must currently be euthymic (HAM-D< 10) and without significant anxiety symptoms
(HAM-A<10). These scales will rely on retrospective reporting from the participant.

Subjects must have had no sexual dysfunction prior to taking an antidepressant and there
must be a clear temporal relationship between the sexual dysfunction and the antidepressant
treatment. Sexual dysfunction occurring as a symptom of the depressive disorder for which
the antidepressant treatment was initiated is not considered to be a pre-existing condition
under this definition.

- Subjects must meet at least one of the following criteria:

- Inability to have an orgasm (anorgasmia), according to patient opinion

- Clinically significant orgasm delay with masturbation or intercourse that
according to patient opinion represents a meaningful delay and interferes with
subject's sexual function compared with the subject's usual time to achieve
orgasm in response to sexual stimulation prior to antidepressant medication

- Inability to attain or maintain until completion of sexual activity an adequate
an erection or lubrication swelling response of sexual excitement that, according
to patient opinion, interferes with subject's sexual function, compared to prior
to antidepressant medication.

- Decreased libido according to patient opinion (and verified by objective
measurements)

- Subjects must experience at least one of the above criterion items with distress and
or disability.

- Subjects must be having or had been having some form of regular sexual activity
(masturbation, oral sex, intercourse) at least twice monthly prior to the
antidepressant treatment and are willing to continue efforts at sexual activity at
least once weekly for the duration of the study

- Subjects must be in good general physical health

Exclusion Criteria:

- Primary or prior diagnosis of a sexual disorder (other than the side effect of the
antidepressant drug or symptom of major depression)

- Sexual dysfunction secondary to general underlying medical condition

- Any uncontrolled psychiatric disorder

- Alcohol or substance abuse or dependence within the past six months

- Recent major relationship changes, disruption, or turmoil ongoing or anticipated which
are unrelated to their sexual dysfunction

- Hamilton Depression and/or Anxiety Scale score (either) >10

- Blood pressure outside the range of 90/50 - 170/100

- Use of investigational drugs within prior 3 months or during study.

- Current use of other drugs for antidepressant induced sexual dysfunction or other
therapies or medications to treat sexual dysfunction

- Hormone replacement therapy, unless patient has been on stable dose of hormone therapy
for at least 3 months prior to the antidepressant treatment and had no sexual
dysfunction while on the same hormone therapy regimen, and there is no change in the
hormone replacement therapy during the study

- Pregnancy, lactating, or planning to become pregnant during the study

- Child bearing potential subjects unwilling and/or not prepared and/or who are judged
unreliable to use an acceptable and verifiable form of contraception during the study

- Any clinically significant abnormality of the screening physical examination

- History of elevated PSA levels that are greater than 0.2 (as defined by MGH labs)

- History of prostate or other hormonal cancers

- Prior use of maca for at least two weeks

- Infection of the urogenital tract that may make sexual activity painful or difficult

- Subjects whose sexual partners are suffering from and/or receiving treatment for
sexual dysfunction

- Receiving psychosexual or other therapy for sexual dysfunction and not willing to
discontinue that treatment at screening

- Subjects not attempting some form of regular sexual activity at least twice monthly
and at least once weekly during study visit intervals for the duration of the entire
study

- Changes in antidepressant agent and/or dose of prescribed antidepressant agent.