NEW HARVARD RESEARCH (9/10) Amer J of Psychiatry

For major depression, the supplement SAMe may succeed where drugs fail

SAMe is one of our Top 10 Recommended Supplements for Optimal Health: SAMe is a natural supplement that has many benefits

New Harvard Study: SAMe effective in rescuing medication failures in TREATMENT RESISTANT DEPRESSION

Mild depression can be successfully treated with alternative therapies such as St. John’s Wort and folic acid (the active forms of folic acid).

But what about major depression? For a condition like that, you’re going to have to forget supplements and rely on powerful drug therapy, right?


New evidence shows that when drugs fail, that’s when SAMe can really save the day.   LINK TO PURCHASE SAMe


SAMe is made naturally in our bodies. It is a natural chemical needed to run our major biochemical pathways, thus it may have beneficial effects other than mood: liver health, pain/inflammation, and joint health.

Brain chemistry imbalance is a common cause of depression. Balance can often be restored with the basic raw nutrients your brain needs.

Most of the nutrients commonly recommends for depression are: omega-3s, vitamins B-6 and C, evening primrose oil or flaxseed, 5-HTP (the precursor material the brain uses to make serotonin), and S-Adenosyl-L-Methionine, which is SAMe.

SAMe increases serotonin and dopamine neurotransmitters in the brain.

Prior research suggests that SAMe may relieve depression just as well as powerful antidepressant drugs. So researchers at Harvard School of Medicine mounted a study to test SAMe in more than 70 patients with major depressive disorder.

Harvard: all the subjects had FAILED TREATMENT with SSRI drugs.  This is considered TREATMENT RESISTANT DEPRESSION

For six weeks, half the group took 1,600 mg of SAMe daily, and half took a placebo. All subjects continued to use whatever medications they were taking at the outset of the study.

Response and remission rates were twice as high in the SAMe group compared to placebo. DOUBLE THE EFFECTIVENESS w/ SAMe

Subjects in the SAMe group had no serious side effects, but I should note that when SAMe is taken in high doses (and 1,600 mg per day is very high), some people may experience insomnia, nausea, or restlessness.

Dosages of less than 400 mg daily are generally well tolerated and have been shown to help many people feel more energetic, alert and focused. LINK TO PURCHASE SAMe

SAMe is a difficult supplement to produce, so it tends to be fairly expensive compared to most dietary supplements. But your body produces SAMe naturally – especially when you have an ample daily intake of folate ,vitamin B-12, and other vitamins.

Details of the Harvard Study

Study findings show value of dietary supplement SAMe in treatment of adults with major depressive disorders

Mass General Hospital study findings published in the American Journal of Psychiatry

BOSTON (August 31, 2010) — A new study conducted by investigators at Harvard Medical School and Massachusetts General Hospital (MGH) suggests that S-Adenosyl Methionine (SAMe), an over-the-counter dietary supplement, can be an effective, relatively well-tolerated, adjunctive treatment for adults with major depressive disorders who do not respond to their treatment with antidepressant medication.

This first-of-its-kind study was published in the August 2010 American Journal of Psychiatry. According to the National Institute of Mental Health, there are approximately 14.8 million people with major depressive disorders in the United States.

The study, “S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial,” is the first randomized, placebo-controlled clinical trial conducted on SAMe in a population of patients with major depressive disorders. A total of 73 adults were enrolled in this six week study and randomly assigned to the placebo control group or the SAMe treatment group. SAMe, in combination with standard depression treatment, was more effective than antidepressant treatment alone in improving measures of depression and remission rates of patients with significant clinical depression. SAMe-treated subjects had a greater response and remission rate to treatment than the placebo-treated group. SAMe was well-tolerated with no reported adverse reactions.

“With each study we continue to gain a better understanding of SAMe’s role in treating depression. This new finding, albeit preliminary and in urgent need of replication, suggests significant, clinically meaningful differences in outcome among patients who had SAMe added to their antidepressant medication treatment compared to those taking a placebo with their medication,” said George Papakostas, M.D., associate professor of psychiatry at Harvard Medical School, director of treatment-resistant depression studies in the Department of Psychiatry at MGH, lead author of the current study. “These findings provide preliminary support for the efficacy, safety, and tolerability of SAMe as an additive therapy for patients with major depressive disorders who do not respond to antidepressant treatment alone. Continued research, however, is urgently needed to more definitively further our understanding of the role of SAMe in the treatment of adults diagnosed with depression. Adjunctive SAMe therapy is promising, but cannot yet be recommended for wide-spread clinical use,” said Papakostas.

The National Institute of Mental Health funded the study. LINK TO PURCHASE SAMe

To date, at least 40 clinical trials have been conducted on SAMe directly and in combination with traditional antidepressant medications. Studies have evaluated SAMe’s use in naturally restoring a healthy mood to the most recent research for treating major depressive disorders.

This current study follows a pilot study published in 2004 in the Journal of Clinical Psychopharmacology, which concluded that antidepressants used in combination with SAMe were significantly more effective in relieving depression than medication alone.

In an accompanying editorial, J. Craig Nelson, M.D., professor of psychiatry at the University California, San Francisco, wrote, “The study of Papakostas, et al. is persuasive. It is the first adjunctive treatment trial of SAMe and the first placebo-controlled trial of oral SAMe since 1993. The era of development for new amine reuptake inhibitors appears to be coming to a close. Some novel approaches appear to be dead ends. SAMe offers a novel mechanism of treatment action and opens up a new area for future exploration. ”

General Guidelines for SAMe

Following are some general guidelines:  (source:

  • Buy only from a reputable supplier. The over-the-counter market is virtually unregulated. According to an article in USA Today: “The market is getting cluttered with fraudulent product … Some smaller players who want to make a buck are putting labels on bottles of baby powder.”
  • According to Nancy Stedman in The SAM-e Handbook, Nature Made, manufactured in Italy by Knoll SPa, is “the gold standard.” Other brands include GNC (General Nutrition Center), also manufactured by Knoll SPa, Nutralife, Solgar, Vitamin Shoppe, Nature’s Plus, Mothernature, and Life Extension.
  • SAM-e is chemically unstable. Don’t take the pills out of their containers until you are ready to use them.
  • Buy only enteric coated tablets, which prevents SAM-e from being broken down in the stomach, where it is useless.
  • 400 mgs daily (2 x 200 mgs) is the typical starting dose, which can be increased. Most studies have used 1600 mgs daily.
  • Use only under a doctor’s supervision. A doctor may recommend SAM-e in conjunction with other antidepressants.
  • Do not stop taking after your depression has lifted. Like traditional antidepressants, SAM-e is a long-tern treatment, at least four months.
  • Ask you doctor about using if you are pregnant or breast feeding.
  • There is a mania risk for patients who have bipolar.
  • Using alcohol is permissible.

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.

Other Potential Benefits of SAMe

SAMe Research – Potential  Benefits:
• May alleviates depression and cognitive deficit
• May reduce appetite
• May improve neurotransmitter synthesis and receptor binding
Inflammation & Pain
• May reduces TNF-alpha (TNF alpha is high in auto-immune diseases like Rheumatoid; it also is a powerful inflammatory stimulus)
• May reduces fibromyalgia pain
• May reduces joint damage
• May improve joint regeneration in osteo & rheumatoid arthritis due to increased chondrocyte (more cartilage)  numbers
• May improve liver protection from toxins,
drugs and alcohol
• May improve:
•  May increases liver glutathione levels (glutathione is the most powerful anti-oxidant known; glutathione protects the cells from free radicals, toxins, pesticides, metals, and damage)


Suggested Use and Dosing

Initial dosing of SAMe should begin at 200 mg early in the day. SAMe, if taken in the evening, may make sleep more difficult for those with problems with sleep. The entire dose can be taken early in the day. The dose can be increased after 5 days or more, 200 mg at a time, while evaluating its effectiveness. Absorption of SAMe is optimal on an empty stomach, however, taking SAMe with meals may be more clinically efficacious by slowing its delivery into the blood stream and creating a more natural increase in SAMe concentrations similar to that of endogenous, natural production.


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