AIDS Treatment News #159, September 18, 1992
John S. James

Physicians would not have expected yohimbine to be helpful in treating fatigue. A recent computer search, for example, found 3,255 articles, letters, etc. published in medical journals between 1985 and 1992 which mention yohimbine; but only one of these references mentions fatigue, and that did not relate to the yohimbine but to another drug used in that particular study. In addition, there are no references to yohimbine on the AIDSLINE file, suggesting that little or nothing has been published concerning its use in AIDS. (AIDSLINE, published by the U. S. National Library of Medicine, is an online database which includes many conference abstracts as well as selected abstracts and other information from over three thousand medical journals.) Most of the articles on yohimbe describe its use in basic research, not as a drug.

Interviews

We first heard about yohimbine in a January 9, 1992, letter from a person with AIDS. He had been taking Yocon (one of several yohimbine brands available) for one week. He had taken the drug for impotence and was not sure if it had had any effect on that, but "it has changed my life in a big way regarding the fatigue I had been experiencing [since a recent case of MAC, which had been treated successfully]. My productivity has more than doubled...I haven't felt this well since the fall of 1987 before I began to feel ill, and was almost devastated by simultaneous PCP and TB in January 1988."

We were unsure what to do with this information, since we could not publish it without confirmation. We decided to wait to make sure the drug was still working weeks or months later. We temporarily lost contact with the patient, but reached him again in early September. He had continued to feel good until March, when he became depressed, and was diagnosed with toxoplasmosis. He stopped using yohimbine during the toxoplasmosis treatment, and started again about six weeks ago, reporting that the drug still works; he is "feeling incredibly well" and plans to spend most of the winter in Europe. "I don't see death in front of me like I used to." We asked about his general health. Five years ago his T-helper count had been 6; except for a temporary rise to about 60 after starting AZT, it has been near zero for five years. Still, he "looks perfectly healthy...I don't know what has been keeping me going." He has been taking acyclovir and pentoxifylline "since the beginning"; he is seeing a leading AIDS specialist and "takes all the pills every day." He is on prophylaxis for pneumocystis, TB, and MAC, and also is taking testosterone and Marinol among other medications. He asked his endocrinologist (a different physician) for the yohimbine, and was prescribed it when that doctor did not see any harm in trying the drug.

Our second report on yohimbine and fatigue came from a patient of Marcus Conant, M. D., in San Francisco; he is also a friend of one of the staff of AIDS TREATMENT NEWS. He had had serious fatigue for four to five months, and was able to work only six-hour days (instead of his usually 10 to 12), and then do little else but sleep. All attempts to diagnose the fatigue were unsuccessful. Dr. Conant had heard about yohimbine and fatigue "through the grapevine," and suggested trying it after investigating the drug and finding no reason not to. After starting yohimbine, the patient was back to his baseline energy level almost immediately, and for two to three months had no side effects. But then he started getting "a different kind of nausea and headaches, occasional agitation," so he stopped the yohimbine. (A week later Dr. Conant's office called to recommend that he go off the drug for a time and then re-evaluate the treatment, because there been off the drug now for a month and a half, and some fatigue has returned, although it is not as bad as before. His T-helper count and blood work are the same as before he started yohimbine.

This patient has had no AIDS-defining illness. His T-helper count has been very stable at around 230-250 -- except for one spike, a rise of about 75 one month after starting yohimbine. The rise did not last, however; his count had gone down again to its usual value by the next test.

He summarized his use of yohimbine by saying it had a significant impact on his life and health. "A long period of severe fatigue can cause despair, pessimism, and resignation. (Yohimbine) catapulted me out of that...I felt better for a significant time, and still feel better now." He said he might use the drug again.

Next we spoke with Dr. Conant, who has a large AIDS practice in San Francisco, and has prescribed yohimbine for fatigue to three AIDS/HIV patients so far.

Dr. Conant noted that fatigue can have a variety of causes, such as infection, very low T-cells, or depression. He emphasized the importance of physicians making sure they have ruled out known causes of fatigue. "The biggest mistake (physicians) make is to jump to a diagnosis; then a treatable condition may be covered up, when it should have been treated."

He said that his patients have reported that yohimbine was effective in decreasing fatigue; he cannot determine yet if it affected libido. The usefulness against fatigue seems to dwindle after three months. At this time, Dr. Conant said, he can neither endorse nor reject this use of the drug. "If we continue to hear reports of benefits, it will be important to sort out what types of fatigue this drug is useful for."

Cautions, Dose, Availability

The Physicians' Desk Reference notes various precautions and side effects, and should be consulted before yohimbine is used. Particular warnings include not using the drug in persons with kidney disease, nor combining it with antidepressants.

"Generally, this drug is not proposed for use in females and certainly must not be used during pregnancy" (Physicians' Desk Reference, Yocon entry). We do not know if there is any particular danger to women, or if this warning only reflects the fact that U. S. testing and approval was for men. Yohimbine has been successfully tested in women, for purposes including weight loss.

The patients who have used the drug for fatigue so far have used the standard dose, one tablet (5.4 mg) three times a day. The drug is inexpensive.

Yohimbine is also contained in a yohimbe tea, which is sold in health-food stores and used as an aphrodisiac. We have not heard of anyone trying this tea for fatigue.

Research Questions

If yohimbine is confirmed to be useful in treating fatigue (many drugs have a period of early enthusiasm, perhaps due to coincidental improvement by patients, but then are abandoned), a number of important questions will need answers:

* What kinds of patients are likely to benefit? This research could readily be done by community-based groups.

* Could this treatment help in some cases of chronic fatigue which is not AIDS related?

* A question for endocrinologists or academic researchers is whether this unexpected effect of yohimbine could help in understanding part of the pathogenesis of AIDS. This drug has been used extensively in basic research because of its effects in blocking certain receptors; but much of its mechanism of action (especially with the low doses used medically) is not understood. Sometimes an accidental discovery, especially one which is unexpected, opens new avenues for productive research.

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