Sexual Health, Lack of Libido

Pharmacologic Antidotes: Although not approved by the FDA for this particular use, numerous pharmacologic agents have been successfully used for treatment of sexual dysfunction caused by SSRIs. However, most of the information obtained regarding these antidotes has come from anecdotal case reports and not double-blind comparative studies. The treatments that will be discussed include amantadine, buspirone, bupropion, psychostimulants, sildenafil, yohimbine, postsynaptic serotonin antagonists and gingko biloba.

Amantadine (Symmetrel, Endo Labs, Chadds Ford, PA) is a dopaminergic agent used in the treatment of movement disorders. It is thought to reverse SSRI-related sexual side effects by causing increased dopamine availability. [12] Doses of amantadine typically used are 75 to 100 mg BID or TID regularly or 100 to 400 mg as needed for at least 2 days before sexual activity. [19] Side effects include possible sedation and potential psychosis.

Buspirone (Buspar, Bristol-Myers Squibb, Princeton, NJ) is an anxiolytic that has been shown in case reports to reverse sexual side effects. There have been also at least two placebo-controlled studies showing that buspirone improves sexual function: one more effectively than the placebo, the other equally effective. In the placebo-controlled trial, which showed significant difference in sexual response between buspirone and placebo, up to 59% of patients taking buspirone reported improvement, compared with up to 30% of patients on placebo during 4 weeks of treatment. [20] The other study is a randomized, placebo-controlled study involving 57 women who reported deterioration in sexual function during their treatment with fluoxetine that was not present before the initiation of the SSRI. [21] Nineteen women were placed on buspirone, 18 on amantadine, and 20 on placebo. All treatment groups experienced improved overall sexual function, including mood, energy, interest/desire, lubrication, orgasm and pleasure. There were no statistically significant differences among the three groups. Several mechanisms have been proposed to explain the reduction of SSRI-induced sexual side effects with buspirone. These mechanisms include (1) partial agonist effects at serotonin-1A receptors, (2) suppression of SSRI-induced elevation of prolactin, (3) dopaminergic effect, (4) the major metabolite of buspirone is an a2 antagonist which has been shown to facilitate sexual behavior in animals. [5]{mosbanner:id=1:right:0}

Bupropion (Wellbutrin, Glaxo Wellcome, Research Triangle Park, NC) is an antidepressant that is hypothesized to have norephinephrine- and dopamine-enhancing properties. [12] In one study, the changes in sexual functioning and depressive symptoms were examined as patients transitioned from SSRIs to bupropion over an 8-week course. [22] The study included 11 adults (8 women and 3 men) who experienced a therapeutic response in regards to their depression, but also complained of sexual side effects on their SSRIs (paroxetine, sertraline, fluoxetine, and the SNRI venlaxafine).

Depression and sexual function were assessed at baseline, 2 weeks after bupropion SR was added (combined treatment), 2 weeks after the taper of the SSRI was initiated and completed, and then after 4 weeks of only bupropion SR therapy. Five patients withdrew during the study secondary to side effects. The conclusion showed that bupropion SR was an effective treatment for depression, and also alleviated overall SSRI-induced sexual dysfunction, particularly libido and orgasm problems; however, some patients cannot tolerate the new side effects.

In a randomized, double-blind, placebo-controlled, parallel-group study, bupropion SR was compared with a placebo in treating SSRI-induced sexual function. [23] Thirty-one adults were enrolled in the study and only one patient dropped out secondary to side effects. The results showed no significant differences between the two treatments related to depression, sexual dysfunction, or side effects.

Clinicians must be aware of the potential drug interactions when combining SSRIs and bupropion. [5] Numerous case reports have documented serious side effects such as tremor, anxiety, and panic attacks, mild clonic jerks and bradykinesia, delirium, and seizures. Fluoxetine can inhibit both the cytochrome P450 3A4 and CYP2D6 hepatic isoenzymes that are believed to be responsible for the metabolism of bupropion and one of its major metabolites, hydroxybupropion.

Stimulants, such as methylphenidate, dextroamphetamine, and pemoline have been shown in case reports to be effective in alleviating SSRI-induced sexual dysfunction. [5,12] Some reports recommend use one hour prior to sexual activity, while others report adding the stimulant to the medication regimen. Low dosages may enhance orgasmic function; however, higher doses have been reported to have the opposite effect. Usual precautions when prescribing stimulants should be considered, such as abuse potential; insomnia if late-day dosing is used; cardiovascular effects; and the possibility of increasing sympathetic tone, which may impair erection in men and pelvic engorgement in women.

Gingko Biloba Extract, an extract from the leaf of the Chinese gingko tree that is sold over-the-counter, has been shown to increase blood flow. [5,12] In one non-blind study, the rate of response ranged from 46% with fluoxetine to 100% with paroxetine and sertraline. [25] Effective doses ranged from 60 mg/day to 240 mg/day. Common side effects include gastrointestinal disturbances, flatulence, and headache, and it can alter blood clotting time.

Yohimbine, a presynaptic a2-blocker, has been reported as effective in treating decreased libido and anorgasmia caused by SSRIs. [26] The mechanism of action is unclear, but may involve the stimulation of adrenergic outflow with increased pelvic blood flow. Effective doses range from 5.4 mg to 16.2 mg taken as needed 1 to 4 hours before sexual intercourse. Common side effects include nausea, anxiety, insomnia, urinary urgency, and sweating.