She's a young woman from the South Shore, finally
able both to work and to study for an advanced degree.
But for years, she's been plagued by severe
depression that stems, she says, from physical abuse she suffered as
a child, and from sexual abuse when she was 17.
She tried Prozac and, by her count, 30 other
antidepressant drugs. Nothing worked. Psychotherapy helped some, and
still does, but not enough.
She's been suicidal. She still has nightmares and
flashbacks. Until a few months ago, the woman, who did not want her
age, occupation or town published, felt she had no options left.
Then she tried SAM-e, the European prescription
antidepressant that in recent months has been growing here in
popularity, despite its $10-a-day price tag. The preparation is now
available as an over-the-counter remedy in US health food stores.
"I haven't felt as depressed," says the woman, who
has been taking 800 milligrams a day of SAM-e for several months.
"It sounds corny, but I just have experienced more joy lately."
Neither an herb nor a vitamin, SAM-e (pronounced
"Sammy") is a synthetic form of a chemical made in the body from
methionine, an amino acid, and an energy molecule called ATP. It
helps with dozens of metabolic functions from preservation of cell
membranes to DNA replication.
In fact, it's been studied and used for years in
Italy as an antidepressant. In the US, the potential market for it
is huge - 18 million Americans suffer from depression.
Because it is sold as a dietary supplement, SAM-e
did not have to pass safety or efficacy review by the US Food and
Drug Administration. But because it contains a "new ingredient"
(S-adenosylmethionine), manufacturers must inform the FDA of their
intent to sell it. By law, if the FDA does not object within a
defined time period - and it has not with SAM-e - the new ingredient
may be sold.
It's not at all clear how SAM-e might combat
depression. It does not work as Prozac-type drugs do, by blocking
re-uptake of a brain chemical called serotonin. It may act by
improving the elasticity of cell membranes or by stabilizing
receptors on cell membranes, but this is unproved.
Still, there's evidence that some depressed people
may be low in SAM-e, and that taking SAM-e supplements may help. In
a 1990 study of 30 depressed people, one third had low levels of
SAM-e in the cerebrospinal fluid, says Teodoro Bottiglieri, the
leader of that research and director of the neuropharmacology lab at
Baylor Institute of Metabolic Disease in Dallas.
Several animal studies and one placebo-controlled
human study suggest that SAM-e can boost serotonin levels. Other
evidence suggests SAM-e may also raise levels of dopamine and
norepinephrine, two other brain chemicals often involved in
depression.
But the best - albeit flawed - evidence for SAM-e
comes from a 1994 Italian analysis of pooled data from 13 clinical
trials. Taken together, six studies showed SAM-e was better than a
placebo at reducing depression. The other studies suggested SAM-e
was equal in efficacy to older, tricyclic antidepressants, which
have been shown to be about as effective as newer antidpressants
such as Prozac.
Yet even psychiatrists who recommend SAM-e are
cautious.
"It is not a good first-line drug. It's something
to consider as a possible alternative when other things have
failed," says Dr. Maurizio Fava, a psychiatrist at Massachusetts
General Hospital. So far, he says, most studies are too small to
carry much statistical weight and use poorly defined groups of
depressed patients.
Dr. Scott Ewing, director of the depression and
anxiety disorders clinic at McLean Hospital in Belmont, agrees.
"Every year or so, there's a new antidepressant du
jour. Right now SAM-e is it. A couple of years ago, it was St.
John's wort," he says. But SAM-e research "is not of the highest
quality."
The studies have typically followed patients for
four weeks or less. Since many depressed patients feel better in a
few weeks even taking a placebo, these results may be meaningless. A
study that followed people for 8 to 12 weeks would be more
convincing, say psychiatrists, because the placebo effect often
wears off by this point.
Still, Ewing supports the use of SAM-e in his
patients who can't tolerate side-effects of other antidepressants,
partly because it appears to have few side effects and to be safe.
It may also take effect sooner than standard
antidepressants and may, if taken with them, boost their
effectiveness, he says. But this is unproven, warns Ewing, and there
are other ways to boost the potency of antidepressants for which
there is good evidence.
Dr. Jerry Rosenbaum, associate chief of psychiatry
for clinical research at MGH, keeps SAM-e for "situations where I'm
striking out with the patient on side effects." But even when it
helps, he says, the benefits don't always last.
On the other hand, Dr. Richard Brown, associate
professor of clinical psychiatry at Columbia University in New York,
is an unabashed SAM-e proponent. In his book [see sidebar], Brown
calls SAM-e a "breakthrough supplement" and claims that it "begins
to relieve depression in seven days." In a telephone interview, he
adds that he's now treated hundreds of people with SAM-e.
In order for the body to make SAM-e, a person must
have adequate levels of folate (which in turn is made from folic
acid, a vitamin) and vitamin B-12. (In fact, adding folate to
standard antidepressants may increase their benefit.)
Once it's made, enzymes interact with SAM-e,
causing it to give up a part of its chemical structure called a
methyl group. In particular, SAM-e donates methyl groups to cell
membranes, to big proteins inside cells and to small ones outside
cells like the neurotransmitters serotonin, norepinephrine, and
dopamine.
For instance, when lipids in cell membranes are
well supplied with methyl groups, the membranes remain elastic, says
Bottiglieri. This allows receptors in the membrane, including those
for some neurotransmitters involved in depression, to move around as
they need to, carrying chemical signals.
Still, nobody really understands how SAM-e might
work in depression, so if you try it, do so under a doctor's
supervision, assuming you can find a doctor open-minded enough to
read what research is available.
Because SAM-e is poorly understood, don't try it
if you have manic-depression, because some antidepressants may make
mania worse. It's also important to take tablets that are
enterically coated so they dissolve in the intestines, not the
stomach, where they can be absorbed, and that are foil-wrapped so
they do not absorb moisture.
Also make sure that your SAM-e product contains
1,4-butanedislfonate, a stabilizer. If not stabilized, SAM-e
products can degrade and become useless. In fact, that's what
happened a decade ago when MGH researchers Fava and Rosenbaum did a
SAM-e study with 40 patients.
The study was "a bust," they say, because the
tablets they had ordered from Italy sat unrefrigerated over a hot
weekend at Logan airport. The pills became discolored, suggesting
oxidation, and perhaps because of this, patients who took them did
no better than those on a placebo.
There's also a theoretical possibility that SAM-e
might raise levels of homocysteine, an amino acid that can raise the
risk of heart disease.
And there's one final caveat. Several US
researchers now at the forefront of SAM-e research have in the past
or are now planning to do research supported by Nature Made, which
sells a SAM-e product.
This does not necessarily mean the researchers are
unethical or their findings won't be credible. But it's something to
chew on.
Judy Foreman’s column runs every other week. Past
columns are available on
www.myhealthsense.com.
Listen to her live
call-in webcast radio show every Wednesday night
from 8:30 to 9:30 EST on
http://www.healthtalk.com.
