Yohimbine: Accidental Discovery As Fatigue Treatment?

Yohimbine is a chemical found in the bark of the Corynanthe
johimbe tree and in certain other plants; in the U. S., yohimbine
is available as a prescription drug approved for treating
impotence in men. Recently we interviewed two persons with AIDS
or HIV, and a physician who is treating one of them and two
others, about their successful use of yohimbine to treat severe,
long-lasting fatigue for which no specific cause could be found.
The effect of the drug was rapid and dramatic, leading to a major
improvement in quality of life. Both persons we interviewed
discontinued yohimbine after two to three months, for varying
reasons; one of them has since restarted the treatment.

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 acertainly 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.