While the mild side effects of SAMe are one of its marketed characteristics, the supplement is not without faults. One of the frequently cited side effects of SAMe is inducing mania in patients with bipolar disorder. In one clinical trial, 9 of 11 bipolar patients experienced symptoms of hypomania/mania after supplementing with S-adenosylmethionine.4 In another study, gastrointestinal side effects to include stomach discomfort (19% of subjects) and diarrhea (20% of subjects) were found to be associated with SAMe supplementation.9 Further research should investigate potential risks and/or interactions when combining standard antidepressants with S-adenosylmethionine. All of these are considerations that should be made before implementing its use.
It should be noted that, overall, the literature on the topic of SAMe for depression is lacking and as mentioned previously, much of the evidence is dated. Further, most of the current findings come predominantly from studies with small sample sizes, so it is difficult to be sure of a sizeable effect. More large, randomized controlled clinical trials of high methodological quality should be conducted to explore this question. That being said, the existing evidence does suggest some antidepressant characteristics of S-adenosylmethionine. As with other alternative remedies for depressive symptoms, these findings often support the use of SAMe as an adjunct treatment.10 That is, it may be most effective when used with other treatment strategies. S-adenosylmethionine is not considered a first-line treatment for depression, and therefore should not be used in replacement of seeking medical treatment, especially for individuals with severe symptoms of depression and/or suicidal ideation. That SAMe appears to be fast acting and safe is promising for individuals who may be looking to further improvement in their depressive symptoms, however, it is always recommended that those considering supplementation consult with a physician.
1. Agnoli, Andreoli, Casacchia, & Cerbo. (1976). Effect of S-Adenosyl- L-Methionine (SAMe) upon depressive symptoms. Journal of Psychiatric Research, 13(1), 43-54.
2. Bell KM, Plon L, Bunney WE, Potkin SG (1988), S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry 145(9):1110-1114.
3. Bressa GM (1994), S-adenosyl-L-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl 154:7-14.
4. Carney, M., Chary, T., Bottiglieri, T., & Reynolds, E. (1989). The switch mechanism and the bipolar/unipolar dichotomy. The British Journal of Psychiatry : The Journal of Mental Science, 154, 48-51.
5. Criconia AM, Araquistain JM, Daffina N et al. (1994), Results of treatment with S-adenosyl-L-methionine in patients with major depression and internal illnesses. Current Therapeutic Research 55(6):666-674.
6. Delle Chiaie, Roberto, Pancheri, Paolo, & Scapicchio, Pierluigi. (2002). Efficacy and tolerability of oral and intramuscular S-adenosyl- l-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: Comparison with imipramine in 2 multicenter studies. American Journal of Clinical Nutrition, 76(5), 1172S-1176S.
7. Fava M, Rosenbaum JF, MacLaughlin R et al. (1990), Neuroendocrine effects of S-adenosyl-L-methionine, a novel putative antidepressant. J Psychiatr Res 24(2):177-184.
8. Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH (1990), Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 147(5):591-595
9. Mischoulon, D., Price, L. H., Carpenter, L. L., Tyrka, A. R., Papakostas, G. I., Baer, L., … Fava, M. (2014). A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of S-Adenosyl-L-Methionine (SAMe) Vs. Escitalopram in Major Depressive Disorder. The Journal of Clinical Psychiatry, 75(4), 370–376.
10. Orsolini, L., De Berardis, D., Vecchiotti, R., & Valchera, A. (2015). P.2.f.028 Antidepressant efficacy of S-adenosyl-L-methionine in major depressive disorder. European Neuropsychopharmacology, 25, S450-S451.
11. Rosenbaum JF, Fava M, Falk WE et al. (1990), The antidepressant potential of oral S-adenosyl-L-methionine. Acta Psychiatr Scand 81(5):432-436.
by Callie Patterson
Callie Patterson is a graduate student pursuing a degree in psychological sciences at Northern Arizona University.
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