NEW DRUG SHOWS PROMISE OF FIGHTING DEPRESSION

WASHINGTON (AP) -- An experimental drug appears to alleviate
depression by blocking a mysterious brain chemical -- one that until
now, doctors didn't even know was at work in mental disorders.

The finding by Merck & Co., published in Friday's edition of the
journal Science, could give doctors the first entirely new way to
treat depression in decades, offering hope to patients who get no help
from today's therapies such as Paxil and Prozac.

``This is really very important,'' said Dr. Steven Hyman, director of
the government's National Institute on Mental Health, who is familiar
with the findings. ``To everybody's surprise, it (the new drug) was
robustly effective for depression.''

The drug still needs more extensive testing in humans, however, before
it would be eligible to receive government approval to be sold.

Depression is the nation's most prevalent mental health problem,
afflicting about 15 million Americans at some point in their lives.
Americans spend about $3 billion a year on drugs to battle it. Those
drugs do help many patients.

But they also can cause serious side effects. Also, some 20 percent of
patients get no help from today's medicines, which all target either
serotonin or norepinephrine, brain chemicals called neurotransmitters,
Hyman said. So scientists have long hunted another way to attack depression.

Merck says its new drug, code-named MK-869, may do just that, by
targeting a brain chemical called substance P that until now has been
a mystery.

In a study of 213 patients with moderate to severe depression, Merck
tested MK-869 against Paxil, a popular and effective antidepressant,
or against a placebo. During the six-week study, MK-869 relieved
depression as effectively as Paxil did, but with fewer side effects,
Merck lead researcher Dr. Mark Kramer reported in Science.

Just how MK-869 worked inside these patients' brains remains a mystery
that has doctors intrigued.

Substance P is a neuropeptide, a small protein that helps nerve cells
communicate. It was discovered in 1931, and doctors theorized it might
offer a way of treating chronic pain when they learned it played some
role in alerting nerve cells to tissue damage. Instead, ``it's been a
disappointment,'' Hyman said -- the chronic pain research has failed.

Merck scientists theorized that substance P was playing a role in
``emotional pain,'' based on how animals put in stressful situations
to mimic human psychological stress reacted to higher or lower levels
of the neuropeptide.

Merck designed a chemical that blocks substance P. In animal testing,
company scientists proved that blocking substance P did not affect the
function of serotonin or norepinephrine, the two brain chemicals that
today's antidepressants target. Clearly, it was relieving
psychological symptoms in an entirely new way, so they moved to
testing MK-869 in people.

Based on standard psychological test scores, the experimental drug
helped significantly improve depression in about half of patients
tested, about the same number that Paxil helped.

MK-869 appeared to have fewer side effects. Some 29 percent of Paxil
patients reported sexual dysfunction, a common antidepressant side
effect, vs. just 3 percent of MK-869 patients. MK-869 patients also
reported slightly less nausea, and fewer patients dropped off the
medication because of side effects than did Paxil patients.

Why would it work? Scientists don't quite know, but a hint is that the
part of the brain behind the ears that's important in regulating
negative emotions ``is literally packed with substance P receptors,''
the government's Hyman said.

Merck said it is planning Phase III trials of the drug -- the
much-larger human studies that the Food and Drug Administration
requires for ultimate proof of whether a new drug works.

Hyman said the company should quickly study patients who have failed
standard antidepressants to see if MK-869 will offer the help they
desperately need -- and he cautions that scientists must verify
Merck's findings to be sure that blocking substance P really helps.

Checked-by: Patrick Henry