SAMe for Fibromyalgia


SAMe (S-adenosyl-L-methionine) is found naturally in nearly all bodily tissues and fluids. The concentrations of SAMe are highest during childhood and tend to decrease with age. SAMe is an essential component in over 100 chemical reactions that occur within the body. It is involved in the production, activation, and metabolism of a variety of hormones, neurotransmitters, and proteins. Natural production of SAMe in the body is partially mediated by levels of vitamins B12 and folate; therefore, deficiencies of these vitamins can cause SAMe concentrations to decrease.

SAMe has been widely investigated as a treatment for osteoarthritis and depression, as well as studied for its effectiveness in treating attention deficit hyperactivity disorder (ADHD), build up of bile in the liver (cholestasis), fibromyalgia, and generalized liver disease. SAMe can be administered orally and via injection at a variety of doses. Prior research studies have utilized SAMe in oral doses ranging from 800mg to 1,600mg daily, and injectable doses ranging from 200mg to 400mg.

SAMe has been shown to cause allergic reactions in some individuals, characterized by flushing, red skin, heart palpitations, dizziness and nausea; however, in a majority of studies, SAMe has proven to be well-tolerated by most users. The most commonly reported side effects include nausea, skin rash, anxiety, and hypomania (persistently elevated euphoric mood), hot sensation and itchiness of the ear, dry mouth, heartburn, blood in the stool, mild diarrhea, constipation, increased thirst, increased salivation, frequent urination, gas, and decreased appetite. In trials that utilized SAMe in its injectable form, common side effects have included vein inflammation, increased heart rate, pain at the injection site, arm soreness, flushing, red skin, dizziness, heart palpitations, nausea, itching, hives, and stomach pain. SAMe is not recommended for use during the first trimester of pregnancy or while breastfeeding, due to a lack of scientific evidence regarding its safety in such situations. In addition, SAMe may cause blood sugar levels to drop, therefore patients with diabetes or hypoglycemia (low blood sugar) should use SAMe with caution.

SAMe can adversely interact with various drugs that affect serotonin levels in the body, including the antidepressant medications clomipramine (Anafranil), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), and imipramine (Tofranil), as well as dextromethorphan (e.g., Robitussin), levodopa (a medication used to treat symptoms of Parkinson’s disease), and the painkillers meperdine (Demerol; a narcotic painkiller), pentazocine (Talwin), and tramadol (Ultram). In addition, SAMe should not be taken by individuals who are currently taking a monoamine oxidase inhibitor (MAOI) for treatment of depression, or who have taken an MAOI within two weeks.

SAMe and Fibromyalgia

Several clinical trials have investigated the use of SAMe as a treatment for fibromyalgia symptoms. A 1987 study by Tavoni et al. compared SAMe versus placebo in 17 patients with fibromyalgia. Of these, 11 had significant clinical depression. Following administration of SAMe, the number of trigger points and painful anatomic sites decreased in the group treated with SAMe, but not in those who received placebo. Furthermore, depression measures also improved for the SAMe group but not for the placebo group. Based on their findings, the authors concluded that SAMe was an effective treatment to improve depression and reduce the number of trigger points in fibromyalgia patients (Tavoni et al., 1987). The findings of this study should be interpreted with caution, however, due to the small sample size.

A subsequent study conducted by Jacobsen et al. (1991) evaluated the efficacy of SAMe when administered orally in 800mg daily doses to fibromyalgia patients. Forty-four patients participated in the study, and half received SAMe while the others received placebo (sugar pill). Treatment lasted for a total of six weeks. Tender points, muscle strength, disease activity, subjective patient symptoms, mood, and side effects were all evaluated prior to the start of treatment and then again at the end. The patients who received SAMe showed improvements in disease activity, pain, fatigue, and morning stiffness; however, tender points, muscle strength, depression, and side effects did not differ between the two groups of patients. The authors concluded that SAMe may be of benefit to some patients with fibromyalgia. This study was also limited by a small sample size therefore the results should be interpreted with caution.

One additional study tested the efficacy of SAMe when administered intravenously (through a vein) to fibromyalgia patients. Of the 34 patients enrolled in the study, half received intravenous SAMe in a 600mg dose, while the remaining half received placebo over a 10 day course of treatment. At the end of the study, no differences in improvements were seen between groups with regard to tender points, pain perception, pain on movement, and overall wellbeing, although SAMe did show a slightly favorable effect. The authors ultimately concluded, however, that no global effects of SAMe were demonstrated in the fibromyalgia patients in this study (Volkmann et al., 1997).

SAMe and Depression

A large body of research supports the use of SAMe as a treatment for depression. This is significant for fibromyalgia patients, as depression is one of the most common comorbid conditions associated with fibromyalgia. As such, SAMe may represent an alternative therapy for those who do not wish to pursue, or who do not respond to, traditional prescription antidepressants.

Many studies have shown that SAMe is more effective than placebo and likely as effective as some tricyclic antidepressants, including desipramine (Norpramin) (Bell et al., 1994), imipramine (Tofranil) (Delle et al., 2002), as well as a useful addition to patients who do not respond to selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), and duloxetine (Cymbalta) (Papakostas et al., 2010). It should be noted, however, that some studies have been limited by small sample sizes, varying diagnostic criteria for depression, short duration of treatment, and inadequate study designs. Nevertheless, the American Psychiatric Association does suggest that SAMe may be useful as an alternative to conventional prescription antidepressants for patients interested in complementary and alternative therapies.

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1.        Tavoni A, Vitali C, Bombardieri S, Pasero G. Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study. Am J Med. 1987;83:107-110.

2.        Bell KM, Potkin SG, Carreon D, Plon L. S-adenosylmethionine blood levels in major depression: changes with drug treatment. Acta Neurol Scand Suppl. 1994;154:15-18.

3.        Jacobsen S, Danneskiold-Samsoe B, Andersen RB. Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. Scand J Rheumatol. 1991;20:294-302.

4.        Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-Lmethionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in multicenter studies. Am J Clin Nutr. 2002;76:1172S-1176S.

5.        Volkmann H, Norregaard J, Jacobsen S, et al. Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia. Scand J Rheumatol. 1997;26:206-211.

6.        Papakostas GI, Mischoulon D, Shyu I, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167:942-948.

Work Group for Major Depressive Disorder. Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition. American Psychiatric Association, May 2010 (Published October 2010). Available at:

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