Female Orgasmic Disorder (FOD) and Wellbutrin XL

Background:

Female orgasmic disorder is characterized by a recurrent or persistent difficulty in
achieving orgasm during sexual activity. A study of sexual activity in a representative
sample of the US population ages 18-59 found that 24% of US females complained of
significant difficulty achieving orgasm in the preceding year (Laumann et al, 2000).
Epidemiological studies in Sweden and the United Kingdom have found similar rates of orgasm
disorder.

Studies of drugs with actions of increasing genital vasodilation in response to sexual
stimulation (eg alprostadil, sildenafil, or phentolamine) have generally been found to be
unsuccessful or to have extremely limited efficacy in reversing female sexual dysfunction
(Basson, 2001; Segraves, 2002). High doses of androgen have been shown to increase various
parameters of sexual interest and activity in women after hysterectomy and bilateral
oophorectomy (Schifren et al, 2000) and there is some evidence that oral
dehydroepiandrosterone may increase responsiveness to sexual stimuli in postmenopausal
women (Hackbert & Heiman, 2002).

There have been fewer studies of pharmacological treatment for hypoactive sexual desire
disorder in premenopausal women. Extensive literature indicates that bupropion has a very
low incidence of drug-induced sexual dysfunction (Clayton et al, 2002; Croft et al, 1999;
Segraves & Balon, 2003) and that bupropion may reverse sexual dysfunction associated with
serotonergic antidepressants (Rosen et al, 1999; Kennedy et al, 2002). In addition one
controlled study (Crenshaw et al, 1987) and several clinical series indicate that bupropion
may have prosexual effects in non-depressed females (Modell et al, 2000). A single blind
study (Segraves et al, 2001) found that bupropion increased the frequency of episodes of
sexual arousal and desire for sexual activity in women diagnosed with hypoactive sexual
desire disorder.

A recent multicenter, double-blind, fixed dose study of females with global, acquired
hypoactive sexual desire disorder found evidence that an exposure to 300 to 400 mg
bupropion XL increased orgasm and pleasure as measured by the CSFQ-F. In this pilot study,
all women had total serum testosterone levels within normal limits and were in stable,
non-conflictual relationships. All patients had no evidence of psychiatric disorder and no
evident etiology to their sexual complaint. All were pre-menopausal. The pilot study
observed the effects of drug treatment for four months. Significant change in measures of
sexual orgasm occurred as early as day 28. There are no currently approved pharmacological
treatments for women with orgasmic disorder.

Specific Aims:

The purpose of this study is to delineate the effects of bupropion XL in women with global
orgasmic disorder, using double blind conditions in an 8 week flexible dose multisite
comparison of bupropion XL and placebo. It is hypothesized that bupropion XL will increase
orgasm completion.

The primary objective of this study is to evaluate the effect of bupropion XL on the ease
and frequency of achieving orgasm in sexual activity.

Secondary objectives will be to investigate the effects of bupropion XL on changes in sexual
arousal and sexual pleasure.