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Ginkgo Biloba for Antidepressant-Induced SexualDysfunction

Alan J. Cohen M.D.University of California at San Francisco, San Francisco, California,

USA

Barbara BartlikNew York Hospital-Cornell Medical Center, New York, New York, USA

In an open trial gingko biloba, an extract derived from the leaf of the Chinese ginkgo tree and noted for its cerebralenhancing effects, was found to be 84 % effective in treating antidepressant-induced sexual dysfunctionpredominately caused by selective serotonin reuptake inhibitors (SSRIs, N = 63).Women(n = 33) were moreresponsive to the sexually enhancing effects of ginkgo biloba than men (N = 30), with relative success rates of 91%versus 76%. Gingko biloba generally had a positive effect on all 4 phases of the sexual response cycle: desire,excitement (erection and lubrication), orgasm; and resolution (afterglow). This study originated from the observationthat a geriatric patient on ginkgo biloba for memory enhancement noted improved erections. Patients exhibitedsexual dysfunction secondary to a variety of antidepressant medications including selective serotonin reuptakeinhibitor (SSRis), serotonin and nonrepinephrine reuptake inhibitor (SNRIs) monoamine oxidase inhibitor (MAOIs),and tricyclics. Dosages of gingko biloba extract ranged from 60 mg qd to 120 mg bid (average = 209 mg/d). Thecommon side effects were gastrointestinal disturbances, headache, and general central nervous system activation.The article includes a discussion of presumed pharmacologic mechanisms, including effects on platelet activatingfactor, prostaglandins, peripheral vasodilatation, and central serotonin and norepinephrine receptor factormodulation.

(missing page 140)

see original reference delayed or inhibited orgasm (54%), and ejaculatory failure. Attempts had been made toalleviate sexual dysfunction through other pharmacologic means, including the use of cyproheptadine, yohimbine,amanta-dine, buspirone, or antidepressant dose reduction, without success. Sixty -three consecutive patients wereprescribed ginkgo biloba extract, 40 or 60 mg capsules to be taken twice a day, titrated up to 120 mg bid, astolerated. The average dose was 207 mg per day. Patients remained on their antidepressant medication. After a 4-week trial period, they were reevaluated for symptoms of sexual dysfunction. Response was deter-mined by clinicalinterview and self-reporting assessment by the patients.

RESULTS

Ginkgo biloba was found to be 84% effective in alleviating antidepressant-induced sexual dysfunction. Women (n =33) were more responsive to the sexually enhancing effects of ginkgo biloba than men (n = 30), with relativesuccess rates of 91% versus 76%. Ginkgo biloba appeared to have a positive effect on all four phases of the sexualresponse cycle; desire, excitement (erection and lubrication), orgasm, and resolution (afterglow). All patients whoresponded have requested to continue ginkgo biloba and are quite satisfied with the results. No adverse side effectswere reported, and it appears to be compatible with antidepressant treatment. In addition, many patients reportedspontaneously that they had improved cognitive functioning, mental clarity, and memory. Enhanced energy levelwas also frequently described. These effects were not systematically studied, however. These additional effectsappeared to benefit patients clinically and enhanced patient compliance.

DISCUSSION

Ginkgo biloba, the extract of the leaves of the maidenhair tree, has been used therapeutically in Asia for centuries. Ithas been recognized by the medical establishment in Germany and France, where it is available by prescription forthe treatment of memory impairment and peripheral artery circulatory disturbances. Such extracts are among the

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most commonly prescribed drugs in Germany and France. In 1989, more prescriptions for ginkgo biloba extractwere written than for any other drug, amounting to 5 million prescriptions.

Numerous clinical trials have shown that ginkgo biloba has been effective in treating cerebral insufficiency ingeriatric patients. The mechanism of action by which ginkgo biloba is thought to be effective for these conditionsappears to be in part through active "ginkgolides" terpenoids and flavinoids that appear to inhibit plateletaggregation, neutrophil degranulation, and the induction of oxygen-free radical production. Ginkgo biloba has beenshown to improve cerebral metabolism and protect against hypoxic damage to the brain in laboratory animals. Indouble-blind, controlled studies, ginkgo biloba was shown to be effective in improving the mental performance of

elderly patients. Ginkgo biloba extract resulted in improved reaction time on memory tests in women of reproductiveage. It also led to stronger alpha and beta brain wave patterns.

Ginkgo biloba has been reported to be effective in a host of conditions responsive to improved circulation. Theseincluded the treatment of hearing problems, visual disturbances, edema, varicose veins, leg ulcers, stroke, andintermittent claudication. Ginkgo extract also increases the binding of acetylcholine to brain receptor sites in animalstudies. Reduced acetylcholine binding has been implicated in Alzheimer's disease.

The mechanism of action by which ginkgo biloba reverses antidepressant-induced sexual dysfunction is not yetclear. It may be related to three or more separate actions: (a) enhanced vascular flow to the genitals throughinhibition of platelet-activating factor, perhaps similar to the mechanism by which the extract enhances cerebralperfusion; (b) a direct effect of the extract on prostaglandins, which are known to enhance erectile function; and (c)serotonin and norepinephrine receptor-induced effects on the brain, which have yet to be elucidated. The sideeffects associated with ginkgo's use appear minimal and include stomach and intestinal upset, headache, allergicskin reactions, and potential for increased bruising. Caution should be exercised in patients at risk of hemorrhaging.None of these side effects were clinically significant.

CONCLUSION

Double-blind studies with systematic measurement of sexual function using ginkgo biloba extract are needed toconfirm these initial positive results. The potential of ginkgo biloba to aid in the relief of antidepres-sant-inducedsexual problems, which are pervasive, and its apparent safety, make it a useful addition to current remedies for thissignificant clinical problem.

Journal of Marital and Sex Therapy. 1998 Apr-Jun 24 (2): 139-143.

Courtesy of Alan J. Cohen M.D.

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