Yohimbine for the Treatment of Impotence

July 1999; Volume 2: 78-81

By Teresa Klepser, PharmD and Nicole Nisly, MD

Impotence, also known as erectile dysfunction, is defined as a male’s inability to achieve or maintain penile erection sufficient for satisfactory sexual performance.¹ Available medical therapies include intracavernosal injections of papaverine hydrochloride, phentolamine, or alprostadil; vacuum constrictive devices; vascular surgery; penile prostheses; and sildenafil (Viagra^®).¹ The invasiveness of most of these therapies and the expense of Viagra have sent men to physicians and Internet pharmacies to find a more "natural" approach.

Yohimbine, an alkaloid and prescription drug originally isolated from the bark of the Pausinystalia yohimbe tree, is found in tropical West Africa and the Congo.² Yohimbe bark and yohimbine are currently available by prescription and via the Internet without a prescription.

Disease Prevalence and Etiology

Impotence is estimated to occur in 10-20 million males and more than one half of the males aged 40 to 70 years old experience some degree of erectile dysfunction.^1,3 Erectile dysfunction may be the result of psychogenic or organic factors, and most commonly organic. Psychogenic factors include sexual anxiety, guilt, fear, or feelings of inadequacy. Organic etiologies include drugs and disease states such as diabetes, hypogonadism, hypertension, vascular disease, hypercholesterolemia, and neurogenic disorders.¹

Drug Properties

Yohimbe has been used historically as an aphrodisiac, but also is claimed to exhibit beneficial properties in the management of dysmenorrhea, hypertension, fevers, leprosy, coughs, antidiuresis, and as an anesthetic.^2,4 The yohimbe bark also possesses hallucinogenic properties that become apparent when smoked.⁵

Mechanism of Action

The physiology of erection is based on heightened cholinergic activity, resulting in increased penile blood inflow. Yohimbine, the predominant active ingredient in yohimbe bark, is a centrally-acting alpha₂-adrenoreceptor blocker similar to reserpine. Yohimbine stimulates the release of norepinephrine, increasing cholinergic activity and decreasing adrenergic activity.⁶ Yohimbine is also believed to inhibit the enzyme monoamine oxidase (MAO) which blocks intracellular metabolism of norepinephrine, serotonin, and other biogenic amines, resulting in increased amine concentration in nerve terminals.^4,5 Yohimbine appears to have no effect on testosterone levels.⁷

Clinical Trials

In the 1960s, several studies were conducted to evaluate the efficacy of Afrodex^® for the treatment of impotence.^8,9 Afrodex contained 5 mg of yohimbine, 5 mg of methyltestosterone, and nux vomica extract which contains the active ingredient strychnine. Afrodex was shown to be beneficial in the treatment of impotence; however, it was unknown if one or all three of the ingredients offered benefit in the treatment of impotence.⁸ Two of the three components of Afrodex—yohimbine and strychnine (contained in nux vomica)—were banned in nonprescription drugs by the FDA in 1989.

Eventually, yohimbine was studied as monotherapy for the treatment of impotence. Ernst et al performed a meta-analysis of the double-blind, randomized, placebo-controlled clinical trials (DBRCT) that evaluated the efficacy of yohimbine in men with some form of erectile dysfunction.¹⁰ Studies were excluded if the Jadad scale assessing methodological quality was less than 3 out of 5 possible points for randomization, placebo control, double-blind, withdrawals and dropouts accounted, and validated outcomes.¹¹ Seven trials met criteria and are summarized in Table 1.

Sample size ranged from 11 to 100 males with erectile dysfunction. Cause of erectile dysfunction varied among studies and included organic, psychogenic, mixed, or unknown. Doses of yohimbine ranged between 15 to 30 mg/d. End points were primarily assessed subjectively through self-reported improvement of sexual function. Overall, studies found yohimbine to be beneficial in erectile dysfunction with five of the studies showing a statistically significant difference compared to placebo. The calculated odds ratio (OR) was 3.85 (confidence interval [CI] 2.22 to 6.67), favoring yohimbine over placebo. Side effects were reported in five of the seven studies. The frequency of side effects ranged from 10-30% depending on the study and included hypertension, rash, anxiety, dizziness, increased urinary frequency, gastrointestinal disturbances, and lack of energy. Eight patients withdrew because of serious adverse effects.

Some criticisms regarding the meta-analysis include the variety of erectile dysfunction etiology, age differences between studies, lack of intention to treat analysis, the use of subjective end points, and lack of adverse effects reported. These criticisms weaken the value of these studies regarding efficacy.

No studies evaluating the efficacy of the plant yohimbe have been published.

Adverse Effects

Since yohimbine penetrates the central nervous system in doses lower than those required for peripheral alpha-blockade, side effects may include antidiuresis and central excitation (i.e., agitation, tremors, insomnia, anxiety, sweating, hypertension, tachycardia, nausea, and vomiting).^12-14 There is a case report of 42-year-old black man who developed erythrodermic skin eruption, renal failure, and lupus-like syndrome after ingesting 5.4 mg of yohimbine three times daily for one day.¹⁵ Overdoses of 20-30 mg/d have produced symptoms such as excessive salivation, piloerection, mydriasis, hypo- or hypertension, and death.^6,12

Contraindications/Precautions

Yohimbe is not recommended for use in individuals with hypertension, diabetes, heart disease, and liver disease.^16,17 Yohimbe may exacerbate psychoses in schizophrenic patients.^16,17 Yohimbine is contraindicated in pregnancy, pediatrics, psychiatric illness, patients with renal disease, and cardiac or renal patients with a history of gastric or duodenal ulcer.^2,6,18

Drug and Food Interactions

Yohimbe should not be taken with tyrosine or phenylalanine or with any tyramine-containing food such as cheese, chocolate, beer, aged meats, and wine.⁵ The combination of yohimbe and tyramine may raise blood pressure.⁵ It is also not advised to take yohimbe or yohimbine concurrently with antidepressants, sedatives, antihistamines, caffeine, or amphetamines.^5,14 The mechanism of action of clonidine is nearly opposite to that of yohimbine; therefore, clonidine may reverse the effects of yohimbine.²

Regulation

The German Commission E, the American Urological Association, and the FDA do not recommend the use of yohimbine for the treatment of organic erectile dysfunction.

Yohimbe has been used in Germany for the treatment of sexual disorders, feebleness, and exhaustion.¹² However, the German Commission E does not recommend its use because of the high risk-benefit ratio.¹³ Yohimbine is not recommended by the American Urological Association for the treatment of organic erectile dysfunction because the outcome data indicate a marked placebo effect.¹⁸

In 1989, the Food and Drug Administration (FDA) banned the sale of all nonprescription aphrodisiac drug products due to a lack of efficacy and safety.¹⁹ Ingredients that were banned in non-prescription aphrodisiac products until safety and efficacy could be provided include estrogens, strychnine, yohimbine, mandrake, anise, licorice, zinc, and cantharides such as Spanish fly.

The FDA-approved indications include using yohimbine as a sympatholytic and mydriatic; yohimbine is available as a prescription medication in the United States. Off-label uses for yohimbine in the United States include the treatment of impotence and orthostatic hypotension.⁶

Formulation and Dosage

Yohimbine tablets containing 5.4 mg of yohimbine hydrochloride are available as standardized prescription medication from various small pharmaceutical companies. A manufacturer’s recommended dose of yohimbine is 5.4 mg three times daily. If side effects are experienced, the dose may be decreased to ½ tablet three times daily and gradually increased to one tablet three times daily.^6,14

Despite being declared an unsafe herb by the FDA, yohimbe and yohimbine may be purchased on the Internet for use as aphrodisiacs or weight loss agents. The herb is available as a single or combination product in tablet, capsule, liquid extract, powder, or tincture formulations. These non-prescription products may contain more than or less than 5.4 mg of yohimbine per dose and may not be standardized.

Conclusions

Traditionally and historically, yohimbe and yohimbine have been used in the treatment of erectile dysfunction. The clinical evidence is weak and the side effect profile is dangerous. Yohimbine may be effective for the treatment of organic erectile dysfunction, but at a steep price.

Recommendation

Yohimbe and yohimbine should not be used in self-treatment.^16,17 Patients should avoid Internet purchases of yohimbe and yohimbine because of the absence of standardization and safe monitoring by some manufacturers. Yohimbine could be cautiously considered in patients who refuse other more invasive or more expensive options and have no contraindications or likely drug or food interactions. All patients who still choose to take yohimbe or yohimbine should be monitored for agitation, tremors, insomnia, anxiety, hypertension, and tachycardia.

Dr. Klepser is an Assistant Professor in the Division of Clinical and Administrative Pharmacy at the University of Iowa College of Pharmacy and Dr. Nisly is an Assistant Professor in the Department of Internal Medicine at the University of Iowa College of Medicine in Iowa City.

References

1. NIH Consensus Development Panel on Impotence. Impotence. JAMA 1993;270:83-90.

2. Drugdex Editorial Staff. Yohimbinemini review. In: Gelman et al, eds. DRUGDEX^® System. Englewood, CO: MICROMEDEX; 1997.

3. Goldstein I, Nehra A. How I work up impotence and non-surgical management of impotence and priapism. J Urol 1994;151:30A.

4. Gaby AR, et al. Yohimbe. http://www.mothernature.com/ency/Herb/Yohimbe.asp

5. Herbal Information Center. Yohimbe Bark. http://www.kcweb.com/herb/yohimbe.htm.

6. Yohimbine. In: The Review of Natural Products. St. Louis, MO: Facts and Comparison; 1999.

7. Coleman E. Yohimbe. http://www.hcrc.org/faqs/xyz/yohimbe.html

8. Knodel LC, et al. Yohimbine therapy of impotence. In: Gelman et al, eds. DRUGDEX^® System. Englewood, CO: MICROMEDEX; 1997.

9. Margolis R, Leslie CH. Review of studies on a mixture of nux vomica, yohimbine, and methyltestosterone in the treatment of impotence. Curr Ther Res Clin Exp 1966;8:280-284.

10. Ernst E, Pittler MH. Yohimbine for erectile dysfunction: A systematic review and meta-analysis of randomized clinical trials. J Urol 1998;159:433-436.

11. Jadad AR, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17:1-12.

12. Flemming T, ed. Pausinystalia yohimbe. In: PDR for Herbal Medicines. Montvale, NJ: Medical Economics Company; 1998.

13. Robbers JE, Tyler VE. Yohimbe. In: Tyler’s Herbs of Choice. Binghamton, NY: The Haworth Press, Inc.; 1999.

14. Konawitch PA, ed. Yohimbine. In: Physicians’ Desk Reference. Montvale, NJ: Medical Economics Company; 1999.

15. Sandler B, Aronson P. Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urology 1993;41:343-345.

16. Tyler VE. Yohimbe. In: The Honest Herbal. New York, NY: Pharmaceutical Products Press; 1993.

17. Hebel SK, ed. Yohimbe. In: The Review of Natural Products. St. Louis, MO: Facts and Comparisons; 1993.

18. Montague DK, et al. Clinical guidelines panel on erectile dysfunction: Summary report on the treatment of organic erectile dysfunction. J Urol 1996;156:2007-2011.

19. Drugdex Editorial Staff. Aphrodisiac agent ban1989 FDA mailgram. In: Gelman et al, eds. DRUGDEX^® System. Englewood, CO: MICROMEDEX; 1995.

Which of the following has not been reported as a side effect for yohimbine?
a. Agitation
b. Sedation
c. Tremors
d. Hypertension

Which of the following may reverse the effects of yohimbine?
a. Bromocriptine
b. Aspirin
c. Clonidine
d. Atenolol