Magic Pill or Minor Hope?
Imagine a nonprescription 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, 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.”
While this would have been an unlikely scenario a decade ago, before alternative medicine went mainstream, 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 (about $75 a month).
“I would tend to the side of caution on this,” advises 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,” says 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 Assn. 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 of the symptoms of Alzheimer’s disease. This link to Alzheimer’s is far from established.
And, if that isn’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,” says 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,” says Dr. Shri K. Mishra, director of the Complementary Health Program at USC, who says larger studies that meet strict research standards are needed.
Long-Term Effects Are Not Known
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,” says Dr. Maurizio 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 the 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 UC 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 says. “I think it 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.”
Drug Could Cause Manic Behavior in Some People
Kagan advises depressed patients to first try standard antidepressants and to use SAM-e under the guidance of a physician. Kagan and Fava note that much of their research involved doses of 1,200 to 1,600 milligrams a day--far more than the 400 milligrams recommended on the over-the-counter products and too high to take without medical supervision. Some depressed people who are prone to mania (a contrasting, wildly elevated mood) could become manic on higher doses of SAM-e--something Kagan observed in his study.
Most people, however, experience minimal side effects, such as stomach upset. And because many standard antidepressants can have bothersome side effects, including weight gain and decreased libido, the mildness of SAM-e could be a big draw.
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 says. “It had an immediate effect. The SAM-e seems to eliminate that ‘out of gas’ feeling. I can’t compare its effect to standard antidepressants [because, he says, he did not remain on them long enough], but I can say there is no comparison with the side effects. The SAM-e had no side effects whatsoever.”
Others, like Stamp, also say the substance works fast.
“One of the great benefits it has is the rapidity of onset. That seems to be very compelling,” says Dr. Sol Grazi, an assistant professor at the University of Colorado School of Medicine.
Effective Pain Relief Without Side Effects
Although SAM-e is touted foremost for depression, perhaps the supplement’s best-documented claim is its use in treating arthritis.
“The data is extremely extensive on arthritis,” says Brown, the Columbia University psychiatry professor. “It reduces pain, doesn’t cause gastrointestinal bleeding and it regenerates cartilage, although it takes several months to see this effect.”
In one study of 20,641 arthritis patients in Germany who took SAM-e for eight weeks, 71% improved, Brown says. A study of 108 patients taking SAM-e for two years showed a modest decrease in stiffness and pain. In several studies comparing SAM-e to nonsteroidal anti-inflammatory drugs (such as ibuprofen), SAM-e was tolerated by patients much better.
“I think what it can do for osteoarthritis is remarkable,” says Grazi, author of another new book on SAM-e called “SAMe: The Safe and Natural Way to Combat Depression and Relieve the Pain of Osteoarthritis.” “Instead of destroying cartilage, which all anti-inflammatories do, it helps build up cartilage material. It reduces pain and regenerates the tissue, or at least stems the tide.”
The national Arthritis Foundation, a nonprofit organization, has had so many inquiries about SAM-e that it released a statement last month agreeing that there is sufficient evidence that it provides pain relief.
However, the foundation said there is not enough evidence that SAM-e improves joint health--such as by regrowing cartilage--and discourages arthritis patients from discontinuing traditional treatments in favor of the supplement.
Like all natural products, there are no government regulations to ensure Sam-e’s quality. This is a critical issue because of SAM-e’s chemical instability. Higher-quality SAM-e products are usually enteric-coated and sold in blister packs to keep the pills from deteriorating.
