Evidence is building for the use of SAMe (S-adenosyl methionine) as adjunctive therapy in major depressive disorder. Just this past August, a landmark study by Papakostas, et al, demonstrated the superior efficacy of SAMe when combined with other antidepressant agents (e.g., fluoxetine, venlafaxine, duloxetine) over antidepressant monotherapy.1 Although SAMe has been reported to induce mania in some case reports, there may be a potential role in treatment for bipolar depression as well.2
Previous to this double-blind, randomized controlled trial, SAMe had been shown to have similar efficacy to tricyclic antidepressants such as imipramine in small trials.3 Based on results from the most recent trial, in a group of patients with an incomplete response to conventional antidepressants, six would need to be treated to experience one response and seven would need to be treated to achieve one remission (also known as number needed to treat).1 On the flip side, few adverse effects were reported. However, caution should be used because of the theoretical risk of serotonin syndrome.
In addition, the study results were only analyzed for patients who took the drug exactly as prescribed, which tends to favor the study medication and does not reflect real-life practice.1 Caution is also warranted because exact percent improvements for each group were not reported and only 73 patients were included in the study. The study participants were only tracked for a period of six weeks, making long-term conclusions impossible.
Typical treatment doses are in the 400-1600 mg/day range.
Recommendation: Because SAMe is an affordable nutritional supplement with few side effects, it is a suitable option for patients with major depressive disorder and suboptimal response to standard antidepressant therapy. The jury is still out on a potential role in bipolar depression.