SAM-e for Depression & Anxiety – Is It Effective? [Research Review]

Is SAM-e effective for depression and can it help to balance mood and anxiousness?

SAM-e (S-Adenosyl-L-methionine) is a chemical produced naturally by the body. An amino acid found in foods called methionine is needed for humans to make SAM-e.

Responsible for supporting many cellular functions, SAM-e is already an approved prescription medication for depression in Italy, Russia, Germany and Spain. It is available as a dietary supplement without a prescription in the U.S.

People with depression and liver disease present abnormal SAM-e levels, a discovery prompting researchers to examine the efficacy of supplements in treating these two conditions.

Studies involving depressed patients taking SAM-e show that it can reliably improve symptoms and make work faster and be safer than certain prescription drugs. It also show benefits for joint health, liver function, cartilage and more.

The FDA has not approved SAM-e as a drug for the treatment of depression, anxiety or other mood disorders. As a dietary supplement, manufacturers can promote it to boost mood and support positive emotions, but cannot claim that it has anti-depressant propertie.

Currently, the National Center of Complementary and Integrative Health is supporting studies regarding the role of SAM-e in fatty liver disease not related to cirrhosis and potential role of in reducing risk of colon cancer. [1, 2]

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Mood Supplement

Mood

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How It Works:

• Enhances mood & promotes cognitive health
• Essentual for dopamine, serotonin & norepinephrine metabolism
• Promotes joint comfort & liver health

Dosage:

Between 400 - 1600 mg per day

Safety:

Rated Likely Safe

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SAM-e for Depression and Anxiety

S-Adenosyl-L-methionine (AdoMet, ademetionine, SAM) is a methyl donor that is involved in methylation reactions throughout the body.

Research shows that patients with depression tend to have lower levels of SAM-e in their cerebrospinal fluid compared to control populations. In persons with low levels, use of a dietary supplement may help to improve mood.

Clinical studies performed over 30 years ago with SAM-e seemed to indicate that it exhibited antidepressant effects on human subjects. [3]

A meta-analysis reviewing 25 trials involving over 700 patients found that SAM-e elicited a significantly better response rate from depressed subjects taking tricyclic antidepressants than a placebo.

Another summary of the literature describing the efficacy of SAM-e for depression and anxiety reported nearly 40 trials completed after 2000 states that “antidepressant effects were observed” in some trials.

In other research studies, it “was as effective as the tricyclic antidepressants minaprine, chlorimipramine, nomifensine and impramine” for relieving depression. [3]

Although researchers aren’t sure how SAM-e exerts an antidepressant effect in humans, they believe it stimulates monoamine turnover or monoamine metabolism while increasing 5-hydroxyindole acetic acid, a chemical playing a role in serotonin activity.

SAM-e also increases levels of norepinephrine and dopamine in the brain. [4] These two neurotransmitters are involved in regulating mood, feelings of pleasure, motivation, goal-directed behavior as well as cognitive function.

Despite the positive findings, the NIH states that, “Overall, the evidence that oral SAMe may be helpful for depression is not conclusive.”

Of the 40 studies conducted, they state that many show beneficial effects, but that most clinical trials lasted only a few weeks. They also raise concerns that some of these trials involved a small number of people “and were not of the highest scientific quality.”

Some of the research was conducted in patients who were administered SAM-e via ingestion rather than as an oral supplement. While research shows that it has lower oral bioavailability compared to injections, the use of enteric coated capsules is believed to effectively deliver the compound to the body.

Research Results

Since SAM-e supports several, important metabolic processes, it may support general health and well-being in a number of different ways.

A study investigating the effects of SAM-e in schizophrenic patients found that when given 800 mg of SAM-e daily for eight weeks, patients experienced “reduction in aggressive behavior and improved quality of life”. Female subjects also “showed improvement of depressive symptoms”.

Researchers concluded that SAM-e may be used as an adjunct in the management of aggressive behavior, depression and quality of life in people with schizophrenia. [5]

An analysis of SAM-e trials completed by the Agency for Health Care Research and Quality reported that use of this product “provided clinically meaningful benefits to depressed subjects compared to placebo use. In addition, SAM-e worked as well as tricyclic antidepressants”.

This analysis further found that SAM-e may also offer relief of symptoms stemming from cholestasis of pregnancy and osteoarthritis. [6]

Scandinavian researchers conducted a meta-analysis of SAM-e studies to learn more about the effectiveness of SAM-e for treating depression compared to tricyclic antidepressants or placebos.

Results of their investigation found that subjects experienced a greater response rate to SAM-e, with “global effect size ranging from 17 percent to 38 percent”.

They report that the antidepressant effect was comparable with that of standard tricyclic antidepressants. [7]

Finally, researchers completed an oral SAM-e and placebo-controlled trial involving 15 patients diagnosed with major depression. According to the authors, “results suggest that oral S-adenosylmethionine is a safe, effective antidepressant with few side effects and a rapid onset of action”

However, authors noted that this supplement induced a manic episode in a patient who had no previous history of mania. In addition, they state that these findings offer support for the “role of methylation in the pathophysiology of depression.” [8]

How Long Does SAM-e Take to Work?

SAM-e’s anti-depressant effects take less time to provide depression symptom relief than prescription antidepressants because of its ability to easily cross intestinal walls and quickly increase plasma concentrations.

In addition, oral or intravenous injection of SAM-e appears to cross the blood-brain barrier and enter the cerebrospinal fluid. Effects of SAM-e on depression have occurred in clinical trials within several days to two weeks. [9]

According to Nature Made – the manufacturers of SAM-E Complete – this dietary supplement can start to improve mood within 14 days of taking it.

Dosage and Side Effects

The University of Maryland Medical Center recommends taking 800 to 1600 mg of SAM-e for mood support per day. Some people have reported side effects of supplementation involving nausea, diarrhea, anxiety, headache and heart palpitations.

Because it may cause restlessness and insomnia, users should avoid taking SAM-e at night. People diagnosed with bipolar disorder should not take this product because it could worsen symptoms of mania. [10]

Since SAM-e is known to increase serotonin levels in the brain, it may interact negatively with antidepressants (Prozac, Zoloft, Elavil, Effexor) that also raise serotonin levels.

Taking SAM-e and an antidepressant drug together may produce excessive amounts of serotonin that could cause adverse side effects such as tachycardia, agitation, anxiety and uncontrollable shivering. It should not be taking concurrently with MAOIs, either, as these medications also raise serotonin levels [11]

Consumer reviews of SAM-e are generally positive, with many users claiming it helped improve mood, relieved their depression, reduced fatigue and, in some cases, alleviated arthritis pain and menopausal issues. [12]

Before taking SAM-e to address low mood, depressive thoughts, anxiousness or stress, it is important to consult with a doctor to determine if this supplement is appropriate for you.

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