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New drug offers hope in fighting depression WASHINGTON (September 10, 1998 4:31 p.m. EDT http://www.nandotimes.com) -- 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. By Lauran Neergaard, AP Medical Writer Copyright 1998 Nando.net Copyright 1998 The Associated Press