A Trial of SAMe for Treatment-Resistant Bipolar Depression

Depression in bipolar disorder is a significant source of disease-related debility; with bipolar individuals typically spending three fold as much time depressed as manic or hypomanic. Clinicians treating bipolar disorder often struggle to provide relief from depressive symptoms that are more often treatment resistant than in unipolar depression. To complicate matters further, the risk/benefit ratio of currently available antidepressants is a source of debate within the field of psychiatry. S-adenosyl-L-methionine (SAMe) is a dietary supplement with well-established antidepressant properties. SAMe's mechanism of action remains unclear, but it appears to be distinct from that of conventional antidepressants. The purpose of this study is to examine the effect of these properties on the mood of bipolar subjects with persistent major depression that has been unresponsive to standard pharmacotherapy. An unusual aspect of the current study design is the schedule of SAMe dosing. SAMe tablets will be administered intermittently and in steadily increasing dosages. The purpose of this gradual and intermittent dosage titration is to lessen the risk of antidepressant-induced mania by seeking the minimum effective oral dose of SAMe.