Common Names

  • SAM-e
  • SAMe

For Patients & Caregivers

Not enough research has been performed to say whether SAM-e can treat depression or osteoarthritis.

SAM-e is a compound produced naturally by the human body. It acts on a number of important molecules including hormones, neurotransmitters, fatty acids, DNA, proteins, and cell membranes. It also has anti-inflammatory activity. Scientists are uncertain how SAM-e works in depression, but they believe it may be linked to synthesis of neurotransmitters such as serotonin and dopamine.

  • To treat AIDS-related spinal cord disease
    No scientific evidence supports this use.
  • To treat Alzheimer’s disease
    There are no data to back this claim.
  • To treat bursitis
    Laboratory studies show that SAM-e has anti-inflammatory activity, but human data are lacking.
  • To treat cirrhosis of the liver
    No scientific evidence supports this use.
  • To treat depression
    Clinical studies produced conflicting results or were poorly designed; more studies are needed to evaluate this use.
  • To treat muscle pain
    No scientific evidence supports this use.
  • To treat osteoarthritis
    One clinical trial showed that oral SAM-e is as effective as conventional treatments in treating osteoarthritis.
  • You are taking clomipramine: There is one report of serotonin syndrome in a woman after simultaneous use of clomipramine and SAM-e.
  • Headache
  • Mild stomach upset
  • Flatulence
  • Nausea and vomiting
  • Patients with bipolar disorder may develop manic phase
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For Healthcare Professionals


SAM-e is endogenously produced in the human body from adenosine triphosphate and methionine (1) (2). In the United States, oral supplementation is used primarily to treat depression (6) and arthritis (5) (7), but data are conflicting. Although SAM-e may improve memory-related cognitive symptoms (17), data on whether it is an effective adjunct for major depressive disorder is mixed (16) (27). Another study suggests benefit compared with escitalopram or placebo (20), but its therapeutic potential may be greater in men (21). A recent Cochrane review cites an absence of quality evidence (22), while a meta-analysis suggests adjunctive potential (23).

In other studies, addition of oral SAM-e to injected pegylated interferon alpha (pegIFN alpha) and oral ribavirin improved viral response in patients with chronic hepatitis C (18). Postoperative intravenous SAM-e therapy improved residual liver function in patients with cirrhosis (19). However, in patients with hepatitis C cirrhosis and at elevated risk for hepatocellular carcinoma, oral SAM-e did not improve liver function, or reduce injury or oxidative stress (24). A small open-label study suggests oral SAM-e may be useful as adjunctive palliative therapy in patients with advanced biliary tract carcinoma (25). While generally safe, the therapeutic value of SAM-e in chronic liver disease is limited (26).

Because it is poorly absorbed, enteric-coated tablets are preferred. Outside the United States, parenteral formulations are used to treat fibromyalgia (9), osteoarthritis (14) (15), and tendonitis as well as depression. Adverse effects such as nausea and diarrhea have been reported following initiation of oral therapy.

  • AIDS-related myelopathy
  • Alzheimer’s disease
  • Bursitis
  • Cirrhosis
  • Depression
  • Fibromyalgia
  • Osteoarthritis

SAM-e is endogenously produced from adenosine triphosphate and the amino acid methionine. It is a major, ubiquitous methyl donor to a wide variety of molecules (26), including catecholamines and other biogenic amines, fatty acids, neurotransmitters, nucleic acids, polysaccharides, porphyrins, proteins and membrane phospholipids. Homocysteine is formed through the transsulfuration pathway and is catabolized to cysteine and indirectly to glutathione. Supplementation with SAM-e restores hepatic glutathione (GSH) deposits and attenuates liver injury (26).

The mechanism by which SAM-e might treat depression is unknown, but increased synthesis of neurotransmitters such as serotonin, norepinephrine, and dopamine, may increase responsiveness of neurotransmitter receptors and fluidity of cell membranes in the production of phospholipids.
 (2) (3) (4)

Headache, mild GI upset, flatulence, nausea, vomiting.
Patients with bipolar disorder may develop manic phase.
 (11) (22)

Clomipramine: Serotonin syndrome was reported following concomitant administration of clomipramine and intramuscular S-adenosylmethionine (13).

  1. Baldessarini RJ. Neuropharmacology of S-adenosyl-L-methionine. Am J Med 1987;83:60-5.

  2. Bell KM, et al. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl 1994;154:15-8.

  3. Reynolds EH, Carney MW, Toone BK. Methylation and mood. Lancet 1984;2:196-8.

  4. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;2:137-52.

  5. Cohen BM, Satlin A, Zubenko GS. S-adenosyl-L-methionine in the treatment of Alzeheimer’s disease. J Clin Psychopharmacol 1988;8:43-7.

  6. Osman E, Owen JS, Burroughs AK. S-adenosyl-L-methionine — a new therapeutic agent in liver disease? Aliment Pharmacol Ther 1993;7:21-8.

  7. Iruela LM, et al. Toxic interaction of S-adenosylmethionine and clomipramine. Am J Psychiatry 1993;150:522.

  8. Filipowicz M, Bernsmeier C, Terracciano L, et al. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS One. 2010 Nov 8;5(11):e15492.

  9. Sarris J, Price LH, Carpenter LL, et al. Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial. Pharmacopsychiatry. Jul 2015;48(4-5):141-144.

  10. Galizia I, Oldani L, Macritchie K, et al. S-adenosyl methionine (SAMe) for depression in adults. Cochrane Database Syst Rev. Oct 10 2016;10:Cd011286.

  11. Sarris J, Murphy J, Mischoulon D, et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. Jun 01 2016;173(6):575-587.

  12. Sarris J, Byrne GJ, Bousman C, et al. Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial(). Eur Neuropsychopharmacol. Aug 14 2018 [Epub ahead of print].

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