By SHARI ROAN
Los Angeles Times
Louisville Courier Journal
August 3, 1999


Imagine a non-prescription pill that promised to quickly lift the darkness of depression, ease the pain of arthritis and even help the liver function better.

Now picture 300 psychiatrists jammed into a Washington, D.C., ballroom to learn more about this natural remedy.

And consider the hype - the books, the media coverage and advertising - that could accompany the arrival of a pill that promised so much and had a cute name that sounded like "sammy."

This would have been an unlikely scenario a decade ago, before alternative medicine went mainstream. But a new pill called SAM-e (for S-adenosylmethionine) has been creating a stir since it became available for sale in this country a few months ago.

Unlike other popular, natural remedies - such as St. John's wort for depression and glucosamine for arthritis - which became hits without strong science behind them, SAM-e has debuted in this country with support from some top U.S. scientists.

What's not known is whether consumers and medical doctors will embrace SAM-e or whether it will be viewed as another overly hyped natural product with a very high price tag (about $75 a month).

"I would tend to the side of caution on this," advised Jerry Cott, chief of adult psychopharmacology research at the National Institute of Mental Health in Washington. "It's very expensive. Clearly, if something is very expensive, it requires a higher level of scientific proof before I would give it a try. I'm concerned there is too much motivation for profit on the part of companies selling the product."

Other experts - and many consumers, based on early sales - are intrigued.

"I'm getting a lot of calls from doctors who are interested in this," said Dr. Richard Brown, a psychiatry professor at Columbia University College of Physicians and Surgeons in New York, who gave a lecture on SAM-e last month at the annual meeting of the American Psychiatric Association and wrote a new book on SAM-e called "Stop Depression Now." "It's a little awesome to have the responsibility of saying that SAM-e is really good."

Moreover, part of its appeal is the possibility that it may have wide applications.

While there are studies demonstrating SAM-e's effectiveness for depression and arthritis, some researchers also believe that SAM-e may minimize the pain of fibromyalgia (a mysterious disorder characterized by achiness in muscles and soft tissue), improve liver function and ameliorate some symptoms of Alzheimer's disease. This link to Alzheimer's is far from established.

And if that wasn't enough, SAM-e is said to be a fast acting treatment for depression, sometimes easing symptoms in one to two weeks. It also has few side effects and does not appear to interact with other medications.

"Doctors say nothing can do so much. But there is a reason it can do so much," said Brown.

SAM-e is produced naturally in the body from a substance called adenosine triphosphate, or ATP, and the amino acid methionine, which is found in protein-rich foods and is long thought to have properties that affect mood and mental functions. SAM-e's major role in the body is to release an essential substance, called a methyl group, which fuels dozens of biochemical reactions and accounts for SAM-e's purported vast array of benefits.

Discovered in 1952, there is an extensive body of scientific study on SAM-e, and very few researchers dismiss its therapeutic potential. But there are several reasons why doctors may be wary of advising patients to try SAM-e.

For one, most studies on SAM-e are from Europe, where it is an approved and popular treatment in several countries for various disorders, such as depression and arthritis. And there are few of the large, long-term, randomized clinical trials that U.S. doctors favor.

"It may have some potential benefits, but I'm not very impressed," said Dr. Shri K. Mishra, director of the Complementary Health Program at the University of Southern California, who says larger studies that meet strict research standards are needed.

Others say the substance is of value, but little is known about dosage, long-term effects and how it compares with other medications.

"Nobody has proven definitely that this substance has antidepressant properties, but there is a lot of evidence that it works," said Dr. Mauriezio Fava, director of the Depression Clinic and Research Program at Massachusetts General Hospital in Boston.

Fava was the co-author of a study of 163 patients in Italy who were given SAM-e injections for 15 days. That study, published in the journal Psychiatry Research in 1995, found that depressive symptoms were significantly reduced in more than half the patients after seven days. Other studies have found it is as effective as the older, tricyclic antidepressants. Tricyclic antidepressants, such as desipramine, are effective medications that tend to cause annoying side effects.

No studies, however, have compared SAM-e with more modern SSRI antidepressants. Today, selective serotonin reuptake inhibitors, such as Prozac, are the treatment of choice for depression because of their effectiveness and lower rate of side effects compared with tricyclics.

Others believe that SAM-e does have drug-like effects and therefore should be subject to federal safety review and regulation—not sold over the counter. Dr. Bruce Kagan, a professor of psychiatry at UCLA's Neuropsychiatric Institute, was among a group of American researchers who began a federally authorized study of SAM-e and depression about 10 years ago as part of an effort by an Italian company to investigate the substance.

After an initial small study, which showed SAM-e to be more effective in treating depression than a placebo, Kagan's group was gearing up for a second study (along with researchers at the University of California, Irvine, and Massachusetts General Hospital) when the U.S. Food and Drug Administration stopped the trial because of concerns over the manufacturing of the pills. SAM-e is a very unstable substance that tends to disintegrate if not properly processed.

Kagan said he was disappointed when the research was dropped and all but forgot about SAM-e until he received a telephone call earlier this year that SAM-e was headed to the United States as a dietary supplement—not a prescription drug.

Knoll Pharmaceuticals in Italy produced the SAM-e used in many of the studies and is behind the U.S. launch of the supplement. Knoll's product is distributed by U.S.-based BASF Corp. and sold by Nature Made and GNC.

"I was shocked," Kagan said. "I think is shows there is a major flaw in our regulatory system that something the FDA put on hold as an investigational drug can become freely available without a prescription in health-food stores."

Still, Kagan says he believes SAM-e works for some people and has even recommended it to a few patients who have not responded to traditional therapies.

"I'm happy this is on the market, but this is not the way it should be studied," he said. "It would be better to do it under controlled conditions. The cat is out of the bag."

Mark Stamp, a government research mathematician who lives in Texas, said he tried SAM-e for his mild depression because he disliked the way antidepressants made him feel.

"Part of the appeal of SAM-e was that I felt it would probably have a mild effect, few side effects and I could control the dose," Stamp said. "It had an immediate effect. The SAM-e seems to eliminate that 'out of gas' feeling.