S-adenosylmethionine (SAMe) has been investigated as a potential adjunct therapy for Fibromyalgia Syndrome (FMS) due to its role in methylation reactions, neurotransmitter synthesis, and its potential effects on mood and pain modulation. The scientific evidence supporting its use comes primarily from a handful of small clinical trials conducted since the late 1980s. A 1987 double-blind, placebo-controlled study by Jacobsen et al. found that intravenous SAMe led to modest improvements in pain, fatigue, and mood among fibromyalgia patients. Subsequent studies using oral SAMe preparations, including a 1991 trial by Tavoni et al. and a 1994 review by the Cochrane Collaboration, reported mild to moderate improvements in pain, morning stiffness, mood, and overall well-being, but these effects were not consistent across all patients and trials.

Despite some positive findings, the studies to date have been limited by small sample sizes, short durations, and methodological heterogeneity. Systematic reviews, such as the 2010 Cochrane review, conclude that while SAMe may have a small beneficial effect on pain and depression in fibromyalgia, the quality of evidence is low and further research is needed. SAMe is not considered a first-line or established treatment for FMS, but it may be considered as an adjunct for some patients, particularly those with comorbid depression, after discussing potential benefits and risks with a healthcare provider.