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Could a vitamin make antidepressants work better?

Rating

3 Star

Could a vitamin make antidepressants work better?

Our Review Summary

The story looks at a supplement that contains a derivative of folic acid known as L-methylfolate (brand name Deplin). Although there is a reasonable theoretical basis to think that this supplement might be beneficial for treating depression, there is very little evidence from clinical studies to support its use. With that in mind, we were dismayed to see so many quotes from clinicians who say their patients seem to benefit from the supplement, while so little time is spent discussing the shortcomings of the current evidence base–which are considerable. The story does eventually get to an appropriate message: “clinical evidence is limited”; it’s just that this conclusion may get lost in the clutter of surrounding anecdotes.

 

Why This Matters

About 70% of individuals who complete a course of treatment with antidepressant medication will see a significant improvement (i.e. >50% reduction) in their depression symptoms. However, as the story points out, up to half of those taking medication will not achieve full remission, and some patients do not see any improvement. Other patients are troubled by adverse effects and have to discontinue their medication. Given the huge toll that depression takes on individuals and our society, it is important to investigate medicines that can increase the effectiveness of antidepressants or which can be used as alternatives in patients who do not respond to or can’t tolerate existing drugs.

Criteria

Does the story adequately discuss the costs of the intervention?

Satisfactory

Good job here. The story notes that the monthly cost of Deplin can run as high as $98 and may not be covered by insurance.

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

Not Satisfactory

The story tells us that in one study, “32% of subjects on Deplin had responded, compared with 15% on the placebo.” Although  this is better than saying simply that twice as many patients responded to Deplin as to placebo (which is how some stories would no doubt have communicated this statistic), the story never says how the researchers defined “response” to the medication, which is an important omission. Typically, a “response” means that patients had a >50% reduction on a depression symptom scale, but readers of this story can’t be expected to know this.

In addition, there are other trials with different formulations of folate (some that can be purchased over the counter for pennies per pill) that are relevant to the evidence.  Collectively, these trials raise the possibility that the forumulation (L-methylfolate, folinic acid, or folic acid) may be important.

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

Not Satisfactory

The story notes that patients receiving Deplin during a short-term study reported no increase in side effects compared with those receiving a placebo. However, the story did not mention that there are potential harms associated with the administration of synthetic folate that would not show up in a small, short-term study such as this one. There are concerns, for example, that too much folate might increase the risk for colorectal cancer or hasten cognitive decline in individuals with poor vitamin B-12 status. At the very least, the story should have noted that current studies are not capable of identifying potential adverse effects of long-term Deplin therapy.

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

Not Satisfactory

While we appreciate that the story did try to put a restraining arm on Deplin’s supporters, in the end we don’t feel that it did quite enough to achieve balance. After leading with enthusiastic anecdotes about how Deplin seems to augment the effects of antidepressant medication, the story waits a bit too long to mention the dearth of evidence that supports Deplin as a depression treatment. Two small studies (one of which was negative) really isn’t that much to get excited about when it comes to depression treatment. (For comparison, a recent review identified some 35 trials of fish oil-based supplements–another unconventional therapy for depression that remains quite preliminary.) Moreover, the story doesn’t caution readers that the sole positive trial of Deplin was presented at a recent psychiatry conference and probably hasn’t been subjected to the full peer review that would precede publication in a professional journal.

Does the story commit disease-mongering?

Satisfactory

There was no disease-mongering in this story.

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

Satisfactory

Barely satisfactory. The story included comments from a number of sources, including a company-supported investigator, a representative of a mental health advocacy group, and non-affiliated clinicians. It also did a good job of disclosing relationships with Deplin maker Pamlab where necessary. What we wanted to see more of were comments specifically about the studies supporting Deplin as a depression treatment. Most of the sources talk only about their clinical experience with the supplement or the general concept of using it. We’d like to see a higher priority placed on analysis of the evidence that Deplin works.

Does the story compare the new approach with existing alternatives?

Satisfactory

The story mentions cognitive-behavioral therapy, aerobic exercise and substance-abuse programs as effective alternatives for individuals with treatment-resistant depression. It should also have mentioned electroconvulsive therapy (commonly referred to as “shock therapy”), which is highly effective for depression and should be considered by patients with severe symptoms or when symptoms do not respond to other therapies.

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

Satisfactory

The story accurately describes Deplin’s status as a “medical food” and notes that physician supervision is required while taking Deplin.

Does the story establish the true novelty of the approach?

Not Satisfactory

The story overstates things when it quotes a researcher who says that Deplin represents “a totally new way to look at depression.” A brief search turned up a study that examined a different folic acid derivative (brand name Leuvocorin) for treatment of resistant depression some 10 years ago. And several existing therapeutic approaches, including supplementation with omega-3 fatty acids and the amino acid SAM-e (S-adenosylmethionine), are based on the idea that individuals with depression lack the building blocks needed to manufacture sufficient quantities of certain neurotransmitters. The premise of these approaches is very similar to that which is driving research on Deplin.

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

Satisfactory

This story was not based on a press release.

Total Score: 6 of 10 Satisfactory

Comments (1)

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Anita Soileau

January 11, 2012 at 8:12 pm

I am the Brand Manager for Deplin, and your comments and questions are valid. May I take the opportunity to address a few of them?

Does the story adequately quantify the benefits of the treatment/test/product/procedure?
The WSJ article did not say how the researchers defined “response” to Deplin in the trial, and you are correct that response was defined as 50% reduction in HAM-D baseline scores, a co-primary endpoint.

Does the story adequately explain/quantify the harms of the intervention?
The review stated too much folate might increase the risk for colorectal cancer. Although synthetic folic acid has been implicated in colorectal cancer risk, at this time, there is no peer reviewed literature concerning L-methylfolate and cancer risk. Due to the lack of information, physicians need to take into consideration the benefit/risk ratio in patients with a family history of or diagnosed with cancer prior to initiating therapy with L-methylfolate.

Does the story seem to grasp the quality of the evidence?
You accurately mentioned 2 small studies with L-methylfolate vs. placebo as an adjunctive to an antidepressant. The first study (n=148) was, in effect, a dose finding study conducted with 7.5mg L-methylfolate. Findings were null, thus the second study (n=75) conducted with 15mg L-methylfolate which separated from placebo. We agree that these results are hypothesis generating and that additional research is warranted to confirm these directional findings.

Thank you for the opportunity to respond to your informative review.
Kind regards,
Anita Soileau

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