SAM-e and St John's Wort

Too good to be true?.

by John McManamy


A 1999 book, "Stop Depression Now" by Brown, Bottiglieri, and Colman trumpets on its front cover: "The breakthrough supplement that works as well as prescription drugs in half the time ... with no side effects."

Sound too good to be true? We are told SAM-e has been prescribed in Europe for more than twenty years and that in Italy it outsells Prozac. One of the authors of "Stop Depression Now", a psychiatrist at Columbia University, claims he has used the supplement on his patients with successful results for five years and another author has dedicated his life to research it.

SAM-e - short for S-adenosylmethionine - is a molecule found in our bodies and is vital to a process called methylation, where one molecule passes a methyl group (one carbon and three hydrogen atoms) to another molecule. It's a transaction essential to more than a hundred processes in the body, from the brain to the bones. Levels of SAM-e are notably lower amongst depressed people of all ages.

Because of the universal nature of methylation, SAM-e has also been found to work well for arthritis and the liver, and may have other yet-to-be discovered uses. As to how the process applies to the brain, scientists still don't know. Their best guess is that SAM-e may affect neurotransmitters such as serotonin and dopamine or their receptors, but then again they could be wrong.

A 2002 meta-anaylasis of 28 studies commissioned by the Agency for Healthcare Research and quality, part of the US Department of Health and Human Services, found that SAM-e reduced HAM-D depression scores by 5.6 points, equating to a "clinically significant" partial response. The same analysis found that 11 studies that compared SAM-e to antidepressants lacked sufficient evidence to determin whether SAM-e was superior or inferior in efficacy to an antidepressant,

The authors of Stop Depression Now are quick to note that SAM-e may not be for everyone, and that deeply depressed or suicidal people should only take the supplement under a doctor's supervision. But they do set out a program for self-treatment for the rest of the population, especially for those who are not inclined to seek help in the first place. Perhaps easy access to SAM-e is a boon to these people, particularly if their other option is to suffer in silence, but for the purposes of this article anyone who acts as his own doctor has a fool for a patient.

SAM-e - Do's and Don'ts

Following are some general guidelines:

And finally bear in mind how complex and subtle and downright mischievous depression actually is. Even if there is a magic bullet and even if that magic bullet is SAM-e, all your problems will hardly crumple overnight in the face of a pill-induced methylation onslaught. SAM-e is not retroactive. It will not replace your bad memories with good ones, nor will it take over the heavy lifting in changing sad thoughts to happy ones. But it may get you back on your feet again. It may, like more traditional antidepressants, bring you back from the living dead, and that certainly is a start.

St John's Wort for Depression

The active ingredients in St John's wort are hypericin, extracted from the flowering tops of the plant, polycyclic phenols, and pseudohypericin. Because it is available in the US as an over-the-counter herbal remedy rather than as a drug (as in the case in Europe), there is virtually no government oversight. Unscrupulous suppliers market the herb as a happy pill, often with smiley faces, and leave the side-effects (most notably, sensitivity to sunlight) off the label.

It gets worse: Again, owing to lack of regulation, consumers cannot be guaranteed evenness in quality or quantity from batch to batch or manufacturer to manufacturer. A 1998 "LA Times" investigative piece found wide discrepancies between the potency claimed on many labels to the actual contents inside the containers.

Wait, there's more: St John's wort may be called "nature's Prozac," but its active ingredient does not work that way. In fact, no one knows how it works, other than it does optimize serotonin activity in the brain. It may be natural, but it is still a powerful drug. Anything that can work on the mind and hold off a force as mighty as a depression - even a mild one - should not be considered a mere herbal remedy. Taking it without a doctor's supervision can be dangerous, especially if one mixes it with other drugs or antidepressants, doubly so in light of the FDA's 2000 advisory that warned of the risk of dangerous interactions with St John's Wort, an over-the-counter remedy used in the treatment of depression, and indinavir, a protease inhibitor used to treat AIDs. The advisory also warned against possible interactions with other protease inhibitors.

In addition, "St. John's wort appears to be an inducer of an important metabolic pathway, cytochrome P450," where many prescription drugs are metabolized. Accordingly, the advisory also warns against possible interactions between the herb and drugs used to "treat conditions such as heart disease, depression, seizures, certain cancers or to prevent conditions such as transplant rejection or pregnancy."

Syndicated health columnist Richard Harkness describes how St John's wort interacts with other drugs:

A 2003 University of South Carolina study found 900 mg a day of St John’s wort over 14 days resulted in a two-fold decrease in plasma concentrations of the sedative Xanax. Because the metabolic pathway affected – CYP 34A – was a common one, the authors of the study concluded: "This suggests that long-term administration of St John's wort may result in diminished clinical effectiveness or increased dosage requirements for all CYP 3A4 substrates, which represent at least 50 percent of all marketed medications."

But there is little doubt as to the herb's effectiveness, at least for mild to moderate depression (dysthymia): Some 27 published clinical studies show a 56 percent improvement rate in depressed patients compared to 25 percent in the placebo group. Additionally, St John's wort compares favorably to other antidepressants.

Nevertheless, there are key weaknesses in all these studies. For one, the trials tended to be short, sometimes as little as four weeks, and did not match St John's wort against the SSRIs. Nor did they test the herb's effectiveness in those suffering from severe depression. That test would come soon enough:

In April 2001, a study funded by Pfizer, which manufactures Zoloft and a St John's wort extract, of 200 adult outpatients with major depression in 11 centers throughout the US over eight weeks found that St John's wort "failed to produce significant differences vs placebo."

Twelve months later, a large study testing remission for severe depression found the placebo beat both St John's wort and Zoloft. The study's authors provided ready excuses for Zoloft's poor performance, but seemed willing to leave the weed hanging out to dry.

But not everyone's depression is super-sized. A 2002 study published in the AJP of 375 patients with mild to moderate depression found St John's wort "produced significantly greater reduction" in depression scores.

St John's Wort Do's and Don'ts

In the meantime, it pays to abide by some common sense guidelines:

Updated Feb 10, 2008

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