SAM-e Dosage for Depression

SAM-e (S-Adenosyl-L-methionine) is a naturally occurring molecule distributed to virtually all body tissues and fluids. SAM-e helps regulate your brain chemicals known as neurotransmitters. Using a process known as methylation, S-adenosylmethionine donates methyl groups to other chemical compounds, assisting in the synthesis of neurotransmitters, hormones and more. When S-adenosylmethionine, is low in the body, less dopamine and serotonin is produced. Being insufficient in either methionine, folate or vitamin B12 may reduce levels of SAMe in your body.


SAMe was first discovered in 1952 in Italy. In the 1970’s, after an Italian laboratory learned to produce it in cell cultures, SAM-e was researched as an antidepressant. S-adenosylmethionine, known in Europe as the pharmaceutical drug Ademetionine, has been used to cure depression for years. Though reduced levels of serotonin and dopamine are associated with depression, these chemicals cannot be taken as oral supplements. But, S-Adenosyl-L-methionine is capable of crossing the blood-brain barrier, and may work by enabling the body to make more of these neurotransmitters directly within the brain. Because its encouragement of the methylation pathway, SAM-e may increase serum levels of the neurotransmitters dopamine, serotonin, and norepinephrine.

Massachusetts General Hospital scientists have evaluated the efficiency of oral SAMe in combination with antidepressant drugs. Seventy-three patients with treatment-resistant major depression were randomized to take SAMe  or a placebo. Both groups continued to take their SSRI. Found that SAMe, in combination with standard depression therapy, was more effective than antidepressant treatment alone in improving measures of depression and remission rates of patients with significant clinical depression.

The 2009 Journal of Clinical Psychiatry published that when given by injection, S-adenosylmethionine, has been found to be as effective as some antidepressant drugs and more powerful than a placebo in the therapy of major depression. Nine people given intravenous SAMe and nine given low oral doses of imipramine were compared in a double-blind design for 14 days. The SAMe produced superior results by the end of the first week of therapy. By the end of the second week, 66 percent of the SAMe patients had a clinically important development in depressive symptoms, compared to 22 percent of the imipramine patients.

The researchers studied the antidepressant efficiency of oral SAMe in a randomized, double-blind, placebo-controlled trial for 15 inpatients with major depression.The findings suggest that oral SAMe is a safe, effectual antidepressant with few side effects and a rapid onset of action. S-adenosylmethionine, is a safe, efficient therapy for depression among people living with HIV. A study reported in the November 2004 edition of “BioMed Central Psychiatry” treated depression and anxiety in AIDS patients with dosages starting at 200 mg twice a day, increasing to as much as 1600 mg twice a day over the eight week course of treatment. The researchers concluded that SAMe was safe and efficient for patients living with HIV.

SAM-e Dosage for Depression

A typical recommended dose of SAMe is 400 mg taken 3 to 4 times per day. According to the University of Maryland Medical Center (UMMC), the recommended daily dose for depressed individuals is 800 mg to 1,600 mg per day. Starting with a low dose and increasing slowly helps prevent stomach upset. Some experts recommend taking oral SAMe with folic acid, vitamin B12, methionine and trimethylglycine to enhance absorption.

Side Effects

S-adenosylmethionine is contraindicated in individuals with a history of mania or bipolar disorder.

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