Read Original Story

Study Shows SAMe May Ease Depression


3 Star

Study Shows SAMe May Ease Depression

Our Review Summary

Without explaining the novelty of this new research, we’re given the hope without the real reason. The piece provides a number of important specifics about the evidence and tries to wrap the study in historical and geographical context. But there are enormous holes in that context, which we point out in this review — enough holes that the novelty of this particular study is a total mystery. It’s unclear how it fits into the prior evidence base that’s described, nor what it means that the supplement is already widely used for depression in Europe. (Spoiler: The true novelty is that this is the first placebo-controlled trial in which oral SAMe was added to antidepressant therapy.)

The blog also oversells the meaning of this preliminary research, failing to add much balance to the lead author’s unbounded hopes, overtly drumming up public excitement for something that hasn’t been proven. “The research offers hope to patients who haven’t been helped by traditional antidepressant treatment.” This statement is almost a slogan, and it’s unnecessary considering that this was a single, small, early, short-term, single-center study of a select group of nonresponders. But because this is the NY Times, the research will offer hope to readers…because the NY Times told us so.


Why This Matters

This matters because treatments for depression are only moderately effective.  About 65-70% of patients respond (>=50% drop in symptoms) after 1-2 adequate treatment trials but a smaller proportion remit.  There is a clear need to find better treatments and/or better ways to implement existing treatments.


Does the story adequately discuss the costs of the intervention?


There’s a nice summary of costs and lack of insurance coverage, citing the editorial.

However, we were surprised to see in this summary that “the cost is relatively low” when the cited editorial states “SAMe is relatively expensive.” This mistake may have been unintentional, and while it’s the exact opposite conclusion of the one in the source, we are inclined not to dock the article a point because the rest of the summary provides balance about copays and, most importantly, tells its readers the absolute monthly cost of the supplement.

Does the story adequately quantify the benefits of the treatment/test/product/procedure?


We’re given the proportions of the active and control groups who showed improvement and experienced complete remission. The piece could’ve been more specific about what improvement meant.

It was too vague when summarizing the 2002 AHRQ analysis that found “clinically meaningful benefits” and that SAMe worked “as well as tricyclic antidepressants.” (See our comments on Novelty.)

Does the story adequately explain/quantify the harms of the intervention?

Not Satisfactory

It only tells us that long-term safety in this setting is unknown. Since the study’s benefits were presented, safety results should’ve been mentioned too. The study itself states that there were no serious adverse events, the SAMe and placebo groups had similar rates of discontinuation due to intolerance, and the SAMe group had a statistically significantly greater increase in blood pressure when lying down, an effect which “if confirmed in future studies, may be of clinical relevance.” 

At least, it could’ve discussed if there are potential harms associated with SAMe in general. The editorial states that SAMe, like most antidepressants, carries a warning that it may induce mania in patients with bipolar disorder. This study was too short and too small to detect adverse events that emerge from longer-term use.

Does the story seem to grasp the quality of the evidence?


The piece tells us about the number of subjects, randomization, placebo control, background therapy, length of treatment, and publication in a journal. We were furthermore told what needs to come: replication in a larger study and more research on dosing, side effects, and long-term treatment. For these reasons, we give it the benefit of the doubt on this criterion, but there were some areas for improvement.

There were some unmentioned limitations that make this study preliminary. One is that the study compared SAMe to placebo, not to any real-world treatment strategy used in people who don’t respond to antidepressants. It’s great that it showed promise, but the rosy picture will darken if the benefits prove worse than those of the adjunctive treatments we already use in nonresponders. Another limitation was that several groups of people were excluded from the trial, including those taking non-SSRIs antidepressants.

Ideally, the preliminary nature of this evidence should have been highlighted instead of glossed over. According to the researchers themselves, the study “aimed to provide preliminary evidence,” and the results “justify larger scale, adequately powered tests of efficacy as well as tolerability and safety (for instance, with respect to supine systolic blood pressure and weight change).”

Due to the vague way the 2002 AHRQ study was summarized, it leaves readers with questions about the novelty of the new evidence and its quality. (See our comments under Novelty.)

Does the story commit disease-mongering?

Not Satisfactory

We liked how the story restricted the target population to nonresponders. However, we slap its wrist because it said the study was in adults with depression who failed antidepressant treatment. It was actually major depressive disorder and failure of 6 weeks adequately dosed with a specific class of SSRIs.

Furthermore, it defines “nonresponders” as patients for whom “antidepressants don’t eliminate symptoms.” Eliminate is too strong, and it produces a broader definition of nonresponder than was used in the study. The trial required subjects to have at least a 16 on a particular measurement of depression symptoms, the HAM-D. According to the story, you’d think a nonresponder would be anybody for whom antidepressants didn’t eliminate symptoms (i.e., those with “normal” HAM-D scores). But that wasn’t the case. Antidepressants may have reduced their symptoms and they could still be nonresponders.

The story’s definition of nonresponder is broader than what most clinicians or researchers woul duse; the standard is two or more failed trials.

Does the story use independent sources and identify conflicts of interest?


An independent source was cited, the author of the editorial that accompanied the study. And all conflicts of interest were clearly pointed out. While, by the letter, it meets the standard for this criteria, we note two flaws:

1) The piece could’ve used a lot more balance to the lead investigator’s hopes and excitement for his research. His quotes aren’t challenged

2) A more independent source could’ve been used because Dr. Nelson and Dr. Papkostas have coauthored 3 recent studies together.

Does the story compare the new approach with existing alternatives?

Not Satisfactory

The piece tells us that more than half of patients with depression are nonresponders and doctors are looking for additional treatments to help them. But it doesn’t tell us what is currently done to treat nonresponders, nor does it point out that we are unable to compare the results for adjunctive SAMe to those for other strategies — adjunctive or otherwise — for managing nonresponders. When someone doesn’t respond to an SSRI, as with the nonresponders in this study, are other SSRIs tried or other classes? It goes to the preliminary nature of this evidence that is glossed over. Other options, indeed, include:  changing antidepressants, adding an antidepressant or another psychotropic drug, adding psychotherapy, electroconvulsive therapy and the approved (but less supported by evidence) transcranial magnetic stimulation, and vagal nerve stimulation.  None of these options is mentioned.

Does the story establish the availability of the treatment/test/product/procedure?


We learn that this supplement is available and popular, and we get its costs.  Because the story meets the lowest standard for this criterion, we rule it satisfactory.  However…..

We don’t learn why it’s been widely used for depression in Europe but not in the U.S. That claim of widespread European use is dubious and could lead readers to falsely conclude that Europeans have concluded it is an effective treatment. Following lemmings off the cliff may be programmed into our nature, but the outcome is often undesirable.

And what’s it used for with such great popularity in the U.S.?

Does the story establish the true novelty of the approach?

Not Satisfactory

We learn that SAMe is a naturally occurring molecule in the body that is widely used in Europe for depression and other conditions. We also hear about the proposed ways SAMe might act in the body, and how its action seems different than those of modern antidepressants.

It was good to summarize the prior AHRQ research on SAMe in depression, but it left us more confused than enlightened. It was too vague when summarizing the 2002 analysis that found “clinically meaningful benefits” and that SAMe worked “as well as tricyclic antidepressants.” If its efficacy is already established, why is this 2010 study a “breakthrough” 8 years later? More details were needed about that analysis and the novelty.

Why is it widely used in Europe for depression but not the U.S.? If the 2002 results were so clearly positive, why does the 2010 study open up “many directions of research” and represent a “huge advancement”?

There are answers to these questions, but not in this blog piece. According to the editorial, this study was “the first placebo-controlled trial of SAMe for adjunctive use” and also “the first placebo-controlled trial of oral SAMe since 1993.” The novelty of this research, therefore, has to do with the observed synergy with prescription drugs, the oral route, and placebo-controlled nature of the study

Does the story appear to rely solely or largely on a news release?


We haven’t been able to find evidence that the article relied on a news release. 

Total Score: 6 of 10 Satisfactory


Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.