Not the Same Old ThingSAMe for Depression
Abstract & Commentary
By Russell H. Greenfield, MD, Editor
Synopsis: A unique study pairing the use of a standard SSRI and SAMe against major depression in subjects who had not responded adequately to SSRI monotherapy suggests safety and significant efficacy over a 6-week trial period.
Source: Papakostas GI, et al. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: A double-blind, randomized clinical trial. Am J Psychiatr 2010;167:942.
In the face of a rising prevalence of major depression, troubling answers to questions about the efficacy and safety of pharmaceutical antidepressant therapy, and concern over rates of non-response to antidepressant therapy, the authors of this double-blind, randomized, controlled trial investigated the use of SAMe as additive, augmentative treatment for people with major depressive disorder who had not responded fully to SSRI antidepressant therapy. A single-center randomized, double-blind controlled trial was performed over the course of 6 weeks. Adult subjects had to meet DSM-IV criteria for current major depressive disorder, have a Hamilton Depression Rating Scale (HAM-D) score of at least 16 at both screening and baseline visits, have been treated with an SSRI at adequate dose for at least 6 weeks' duration, and have been taking a stable dose of SSRI for the prior 4 weeks. Subjects with a history of suicidal ideation or mania were excluded.
Participants were randomly assigned to receive either SAMe 400 mg twice daily or matched placebo. Study visits occurred weekly for a total of 6 post-baseline visits. Following the second post-baseline visit, all subjects had their number of pills doubled for the duration of the trial so that they were then ingesting two pills twice daily (1,600 mg of SAMe or 4 placebo pills). SSRI doses remained constant during the 6-week study. HAM-D and Clinical Global Impression (CGI) severity and improvement scales were administered at each visit. Primary outcome measure was difference in response rates between the two treatment arms according to HAM-D ratings. A positive response was defined as > 50% reduction in scores during treatment (or a final score < 7). Secondary outcome measures of interest included continuous change in HAM-D scores and CGI severity ratings during treatment.
A total of 73 subjects underwent randomization (n = 39 in SAMe group) with 55 (75.3%) completing the trial (70.5% of placebo and 79.4% receiving adjunctive SAMe). Per HAM-D ratings, response rates for the SAMe- vs. placebo-treated patients were 36.1% and 17.6%, respectively, and remission rates 25.8% and 11.7%, respectively. Differences were statistically significant and considered clinically meaningful.
A slightly higher mean systolic blood pressure was noted for patients receiving adjunctive SAMe compared with placebo (mean difference = 3.1 mm Hg), as well as a nearly significant difference in weight for subjects on SAMe compared with placebo (members of both groups lost weight during the trial but those in the placebo group lost ~1.5 pounds more). There were no serious adverse events, including no episodes of serotonin syndrome (a concern commonly noted with SAMe).
The authors conclude that their preliminary data suggest SAMe to be a safe and effective add-on therapy to SSRIs for the treatment of resistant major depressive disorder, and call for additional studies of SAMe.
Commentary
This is the point where the editor of Alternative Medicine Alert typically takes his turn appraising the study in question, and offers an opinion on whether or not the results merit clinical consideration; however, in the same edition of The American Journal of Psychiatry appears an excellent editorial1 by J. Craig Nelson, MD, that would be extremely difficult to improve upon and is recommended reading. Nelson notes that there is a paucity of options available when considering adjunctive therapy for people with major depressive disorder who have not responded well to SSRIs. He also points out that upwards of 50% of patients treated with SSRIs may not respond adequately.
A review of the current state of the literature regarding SAMe monotherapy against depression follows, much of which focuses on parenteral therapy, and to a smaller degree oral therapy. In both instances active treatment was shown to be superior to placebo, and comparative trials typically performed with tricyclic antidepressants as the comparator generally showed SAMe therapy to be equivalent in efficacy.
SAMe is a methyl donor that may play an important role in supporting phospholipid cell membrane integrity and optimal production of catecholamines. SAMe crosses the blood-brain barrier, and some data suggest a role for the agent in hepatic disorders and arthritides.
Although the study results are compelling, the few shortcomings are important, the most noteworthy being the significant dropout rate that occurred over the relatively short time frame of 6 weeks, even considering the fact that intention-to-treat analysis was performed.
Confidence in the safety and effectiveness of many antidepressant therapies seems to be falling both among patients and practitioners. On the upside, there has been a growth in interest in other means of preventing and treating mild-to-moderate depression including dietary and fitness methods. Available data suggest SAMe may be a useful stop-gap, if not long-term therapy, because it works relatively quickly when effective. Results like those from the current study serve notice that SAMe might be a useful adjunct to conventional medical care in the treatment of major depressive disorder, a unique role for an intervention until recently considered squarely alternative in nature.
Reference
1. Nelson JC. S-Adenosyl methionine (SAMe) augmentation in major depressive disorder. Am J Psychiatry 2010;167:889-891.
A unique study pairing the use of a standard SSRI and SAMe against major depression in subjects who had not responded adequately to SSRI monotherapy suggests safety and significant efficacy over a 6-week trial period.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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