SAMe boosts antidepressant therapy

Patients with major depressive disorder who fail to respond to treatment with serotonin reuptake inhibitors (SRIs) may benefit from the addition of the nutritional supplement S-adenosyl methionine (SAMe), according to results of the first placebo-controlled trial of the supplement in refractory depression.

"The results of this study provide preliminary evidence suggesting that SAMe can be an effective, relatively well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and our findings warrant replication," the study authors conclude in the August issue of the American Journal of Psychiatry. Included in the single-center, 6-week study were 73 adults with major depressive disorder in whom a prior selective SRI trial had failed at an adequate dose for at least 6 weeks. Thirty-nine were randomly assigned to SAMe (at a target dose of 800 mg twice a day) and 34 to matching placebo, added to their ongoing antidepressant regimen. Fifty-five patients (75.3%) completed the 6-week study: 31 (79.4%) in the SAMe arm and 24 (70.5%) in the placebo arm.

According to the investigators, during the study, significantly more SAMe-treated than placebo-treated patients (36.1% vs 17.6%) experienced a clinical response on the 17-item Hamilton Depression Rating Scale (HAM-D), which was the primary study outcome. Remission rates were also higher with SAMe than with placebo (25.8% vs 11.7%).

An increase in SAMe concentrations has been linked to improvement in depressive symptoms. Low SAMe levels may limit synthesis of brain neurotransmitters such as serotonin, norepinephrine, and dopamine. This may directly contribute to depressive symptoms or interfere with or limit the action of other antidepressants. Administration of SAMe may ameliorate these deficiencies or augment antidepressants and facilitate neurotransmission. The study was funded by a grant from the National Institute of Mental Health.