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Is SAM-E an Effective Treatment for Fibromyalgia?

By: Jacqueline Meaney, PharmD [PGY-1 Resident at Gainesville VAMC in Florida]

Fibromyalgia is a syndrome of chronic pain that affects the musculoskeletal system. Typical symptoms include pain, stiffness, fatigue, insomnia, and tenderness over specific areas. Active depression is seen in one-third of patients with fibromyalgia, and a lifetime history of depression is seen in one-half of fibromyalgia patients.1 It is difficult to determine if the depression seen in fibromyalgia is a cause of fibromyalgia, or a result of coping with symptoms of this disease. Symptomatic control of fibromyalgia is the goal of therapy, since there is no cure. There are many pharmacologic and non-pharmacologic therapies to choose from when treating a symptomatic patient with fibromyalgia, however most of these therapies have not been well studied, or have failed to show statistically significant responses. 2

Treatment strategies for fibromyalgia typically include a combination of medications, lifestyle modification, and self-help strategies such as acupressure and heat therapies. There is no gold-standard of treatment, but self-efficacy and adherence to the treatment regimen have been shown to improve quality of life in fibromyalgia patients.  Medications typically used to treat symptoms of fibromyalgia include analgesics, antidepressants, and GABA-analogues. There are only three medications currently FDA-approved for the treatment of fibromyalgia symptoms. These medications include milnacipran (Savella®), pregabalin (Lyrica®) and duloxetine (Cymbalta®). Exercise is currently recommended as the first step of a treatment strategy for fibromyalgia, since it has been shown to improve well-being, physical function, and pain in fibromyalgia patients.3 In addition to exercise, another common non-pharmacological treatment for symptoms of fibromyalgia is diet modification. In addition to non-pharmacologic approaches, contemporary alternative medications (CAMs) are used in approximately 90% of fibromyalgia patients. CAMs typically have little evidence of efficacy, as studies often report mixed results.4

S-adenosylmethionine (SAMe) is a CAM and a naturally occurring methyl donor compound that plays a role in many chemical reactions in the body. There are over 40 metabolic reactions that involve the transfer of a methyl group from SAMe to substrates such as proteins, nucleic acids, and other metabolites. Along with other contemporary alternative medications such as capsaicin, St. John’s Wort, melatonin, valeria, magnesium, and Siberian ginseng, SAMe has been studied for the symptomatic relief of fibromyalgia. 5

Specifically, the efficacy of SAMe has been studied in seven double-blind clinical trials. Of these seven trials, two trials studied IV SAMe, four studied IM SAMe, and one studied oral SAMe. 5-12 These trials looked at the efficacy of SAMe at doses ranging from 200-600mg daily over a range of 15-42 days. Each trial measured pain points using the Tender Point Scale (TPS), and depression using the Hamilton Rating Scale for Depression (HRSD). In addition, each trial measured additional outcomes that varied between trials, including isokinetic muscle strength (IMS), and additional measures of depression using alternative depression scales. SAMe was effective in decreasing the number of tender points or the severity of tender point scores in five of the seven clinical trials. 5, 7, 9, 11, 12 In six of the seven trials, depression ratings improved in one or more measures (Self Evaluation for Depression, Hamilton Rating Scale for Depression, Zung’s Self-Rating Scale for Depression, or Beck’s Depression Inventory [BDI]). 5-7, 9-12 However, in the seventh trial, there was no significant difference between the treatment group and the placebo group in pain ratings on a Visual Analog Scale, number of tender points, tender point score, BDI score, and physician-rated global assessment of depression. The seventh clinical trial studied 34 patients over the course of 10 days, and demonstrated no statistically significant difference between patients treated with SAMe at a dose of 600mg IV daily as compared to patients treated with placebo. Four of the thirty-four patients withdrew from this study owing to adverse events resulting from SAMe.8

Only one of these studies compared the efficacy of oral SAMe with that of a placebo. In this study, forty-four patients with fibromyalgia were randomly assigned to either the treatment group or the placebo group. The treatment group was given 400mg of SAMe twice daily for 6 weeks. A visual analog scale was used to measure the patients’ pain, morning stiffness, quality of sleep, mood, fatigue, and disease activity. The results of this randomized controlled trial (RCT) demonstrated that improvements were seen in terms of a decrease in clinical disease activity, a decrease in morning stiffness, reductions in fatigue, and improvements in mood among the SAMe-treated patients compared with the placebo group. All of these factors were statistically significant. However, there was no significant difference in tender point score, depression (BDI score) or muscle strength. Mild adverse effects such as stomach upset and dizziness were reported.6, 13

Unfortunately, all seven studies used a small number of subjects (n= 10, 44, 17, 47, 34, 30, and 30). In addition, three studies did not use a placebo control group, and an additional three studies did not control the use of analgesics. Two out of the original seven studies did not show any significant difference in pain when patients were treated with SAMe, 6, 10 and one study did not show any difference in depression.8 The single study that looked at oral SAMe showed a positive effect on fatigue and mood, but no significant effect on pain. 6

In terms of safety, SAMe is typically well-tolerated. Most of the reported adverse effects are short-lived and are of mild to moderate severity. Very few patients have withdrawn from clinical trials due to adverse effects resulting from treatment with SAMe. However, that does not mean that SAMe lacks adverse effects altogether. Adverse effects of oral SAMe include gastrointestinal distress, dizziness, and hypomania. Adverse effects seen with injectable SAMe include transient pain at the injections site, mild psychoactivation, anaphylaxis, nausea, vomiting, and diarrhea. 5

While the efficacy of SAMe for symptoms of fibromyalgia has been evaluated in seven clinical trials, all of these studies were small and demonstrated mixed results. The effects of oral SAMe have only been reported in a single RCT, which demonstrated some positive effects on symptoms of fibromyalgia.13 Furthermore, while SAMe appears to be relatively safe, it is very expensive, and interactions with other medications are not well-studied.14

Larger-scale, placebo-controlled clinical trials are still needed before more definite conclusions can be drawn with regards to the role of SAMe in the symptomatic treatment of fibromyalgia. However, this does not mean that SAMe should not be taken by patients with fibromyalgia to see if it results in a symptomatic relief. Oral SAMe can be clinically efficacious and should not be overlooked as an agent for symptomatic relief in patients with fibromyalgia.15 In a disease like fibromyalgia, where symptoms vary greatly from patient to patient, it is especially important to consider all therapeutic options, since the response to therapy varies greatly as well.4



  1. Sarac AJ, Gur A. Complementary and alternative medical therapies in fibromyalgia. Curr Pharm Des 2006; 12(1): 47-57. Accessed November 4, 2014.
  2. Patkar AA, Bilal LS, Masand PS. Management of fibromyalgia. Curr Psychiatry Rep 2003; 5(1): 218-24. Accessed November 3, 2014.
  3. Busch A, Schachter CL, Peloso PM, Bombardier C. , Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2002;(3): CD003786.
  4. Pioro-Boisset M, Esdaile JM, Fitzcharles MA, Alternative medicine use in fibromyalgia syndrome. Arthritis Care and Research. 1996; 9(1): 13-17.
  5. Fetrow CW, Avila JR. Efficacy of the dietary supplements. S-adenosyl-L-methionine. Ann Pharmacotherapy 2001; 35(5): 1414-25. Accessed November 4, 2014.
  6. Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S- adenosylmethionine in primary fibromyalgia: a double-blind clinical evaluation. Scand J Rheumatol 1991; 20(2): 294-302. Accessed November 7, 2014.
  7. Tavoni A, Vitali C, Bombardieri S. Evaluation of S- adenosylmethionine in primary fibromyalgia: a double-blind crossover study. Am J Med 1987; 83(2): 107-110. Accessed November 4, 2014.
  8. Volkmann H, Norregaard J, Jacobsen S, et al. Double-blind, placebo-controlled crossover study of intravenous S- adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheum 1997; 26(1): 206-11. Accessed November 5, 2014.
  9. Tavoni A, Jeracitano G, Cirigliano G. Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind study. Clin Exp Rheumatol 1998; 16(7): 106-107. Accessed November 3, 2014.
  10. DiBenedetto P, Iona LG, Zidarich V. Clinical evaluation of S-adenosyl- L-methionine versus trans-cutaneous electrical nerve stimulation in primary fibromyalgia. Curr Ther Res 1993; 53(3):222-229. Accessed November 4, 2014.
  11. Grassetto M, Varotto A. Primary fibromyalgia is responsive to S-adenosylmethionine. Curr Ther Res 1994; 55(3): 797-806.
  12. Ianniello A, Ostuni PA, Sfriso P, et al. S-Adenosyl-L-methionine in Sjogren’s syndrome and fibromyalgia. Curr Ther Res 1994; 55(4): 699-706. Accessed November 4, 2014.
  13. De Silva V, El-Metwally A, Ernst E, et al. Evidence for the efficacy of complementary and alternative medicines in the management of fibromyalgia: a systematic review. Rheumatology (Oxford) 2010; 49(6):1063-8.
  14. Ebell MH, Beck E. How effective are complementary/alternative medicine (CAM) therapies for fibromyalgia? J Fam Pract 2001;50(5): 400-1. Accessed November 2, 2014.
  15. Bennett R. The rational management of fibromyalgia patients. Rheum Dis Clin North Am 2002; 28(1): 13-15. Accessed November 4, 2014.

[pubmed_related keyword1=”fibromyalgia” keyword2=”SAM-E” keyword3=”treatment”]

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