S-adenosylmethionine (SAM-e) is a compound naturally found in the body that is involved in methylation processes, neurotransmitter synthesis, and modulation of inflammation. Its use in fibromyalgia syndrome (FMS) has been explored primarily due to its potential antidepressant and analgesic properties. Several clinical trials, most of which were conducted in the 1980s and 1990s, have assessed the effects of oral and parenteral SAM-e in patients with fibromyalgia. Some of these studies reported modest improvements in pain, fatigue, and mood symptoms compared to placebo, but the sample sizes were generally small, study durations were short, and methodologies varied. A 2010 systematic review found that the evidence supporting SAM-e for fibromyalgia was limited and of low to moderate quality, with some indication of benefit for pain and depression but not for other core symptoms such as sleep disturbance or tender points.

Current guidelines, such as those from the European League Against Rheumatism (EULAR), consider SAM-e as a possible adjunct for patients with prominent depressive symptoms, but do not recommend it as a first-line therapy for fibromyalgia due to insufficient robust evidence. In summary, while there is some scientific investigation and modest evidence supporting the use of SAM-e in fibromyalgia—primarily for mood and possibly pain—the overall quality and quantity of data are limited, and its role is not firmly established.