995 S.W. 24 Street, Fort Lauderdale, Florida 33315
February 17, 2000
Sidney M. Wolfe, M.D.
Larry D. Sasich, Pharm.D.
The Health Research Group
1600 20th Street NW
Washington, DC 20009
Re: SAMe - Worst Pills/Best Pills, 1/2000
Dear Drs. Wolfe and Sasich:
This letter is in reference to the unsubstantiated and incorrect information you recently published on the use of S-adenosylmethionine (SAMe) for depression.
The synthetic form of SAMe, a natural substance present in all cells, has undergone 25 controlled clinical trials, 12 of which met the stringent criteria for meta-analysis. In addition, there are 13 published uncontrolled trials of SAMe for depression. The efficacy demonstrated in these trials, without exception, is equivalent or superior to tricyclics and significantly superior to placebo. The safety in these trials, without exception, is far superior to any known drug antidepressant. The most serious side effect reported during the clinical trials of SAMe is perhaps the nausea and vomiting that occurred in a fibromyalgia study, and mania, which has been reported in Parkinson's and bipolar patients.
No evidence is provided in your article to substantiate the accusation contained in the title that SAMe is either ineffective or dangerous, beyond your personal assertion that the four-week clinical trials should have been six-weeks. Antidepressant drug trials were designed in the 1960s based on the length of time it takes for tricyclic antidepressants to work. No evidence exists to support your claim that four weeks is insufficient to test the safety and efficacy of SAMe, a non-tricyclic. According to a European consensus (Woggon, Psychopharm 106 Suppl:S90), four weeks is, in fact, sufficient to test the efficacy of antidepressants, including tricyclics. No sustained effect is demonstrated by either four or six-week trials, a fact acknowledged by all antidepressant drug manufacturers in the Physicians Desk Reference (PDR).
You incorrectly state that there are no known drug interactions with SAMe. In fact, the only serious adverse effect ever reported about SAMe was an adverse reaction in a person taking it and clomipramine together. For this reason, we advise that people do not take SAMe with drug antidepressants without first consulting their physician.
The paragraph from The Medical Letter on Drugs and Therapeutics you cite as evidence that SAMe is ineffective and dangerous is not supported by any evidence. The portion claiming that SAMe manufactured by a drug company and sold as a dietary supplement is different than the same product sold as a drug by the same company is bizarre and unsubstantiated.
We note that this independent source of drug information written for doctors and pharmacists heartily endorses fluoroquinolones for older people with pneumonia and urinary tract infections, that it characterizes the liver toxicity associated with Duract as troublesome with continued use, and concludes that Posicor might cause a little syncope now and then. Unlike SAMe, which this unbiased publication labels as unproven and probably dangerous, none of these drugs suffer any serious rebuke. You've done no less than five articles on the dangers of fluoroquinolone antibiotics: three have been withdrawn from the market, as were Duract and Posicor because they were killing people.
It appears that this unbiased publication holds a different standard for dietary supplements than for drugs. And, strangely, if the dietary supplement is manufactured as a drug-the claim is that if it's labeled as a dietary supplement, it's somehow different. The fact of the matter is that while this publication doesn't take drug company largess, the people who actually write the reviews and the universities they work for do.
You have a consistent and irrational bias against dietary supplements. In the case of SAMe, nothing you say is supported by the evidence. Since your publication does not provide a forum for dissent, we are going to provide one for our magazine and whatever reply you care to provide.
Gary Prater, Vice-President
The Life Extension Foundation
Terri Mitchell, Research Associate
The Life Extension Foundation