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Ketamine for depression: NPR coverage leans too heavily on proponents

Rating

3 Star

Tags

Club Drug Ketamine Gains Traction As A Treatment For Depression

Our Review Summary

Mature man with depressed lookThe use of ketamine to treat depression is worthy of notice, but that means it is also worthy of clear-eyed evaluation. This story gushes with glowing testimonials, but the flow of skepticism is much more limited. A physician-advocate and a grateful patient are highlighted and personalized, while critics receive limited air time and no patients who failed to respond were introduced in any meaningful way. There are trials that have produced remarkable results, but the story doesn’t explain how minuscule, brief, and limited these pilot studies were.

 

Why This Matters

Given the limited effectiveness of available antidepressants, and especially the time it takes for them to start working (3-6 weeks), more effective, faster-onset treatments would be very useful. Ketamine, which may have a different mechanism of action from traditional drugs, appears to be a promising early candidate for such a treatment.

With that being said, readers and listeners of this story would understandably wonder why ketamine isn’t approved for the treatment of depression. And that’s the problem: the story fails to make clear that a few small studies and a pile of selected anecdotes are not the same as a consistent body of evidence from trials that include an ample range of patients and last long enough to see if the initial results are durable.

Criteria

Does the story adequately discuss the costs of the intervention?

Satisfactory

Nice detail here. The story reports that each treatment can cost $500 to $1000 and it is usually repeated every few weeks. The story also reports the treatment is generally not covered by insurance.

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

Not Satisfactory

Perhaps the main reason this story doesn’t quantify the benefits of ketamine for people with depression is that the small studies done so far have only shown that it is possible there are benefits, without fully testing how consistent or durable the effects are. The story does point out that the FDA has not approved ketamine for the treatment of depression and it mentions that the drug “doesn’t always work”, but the most prominent and memorable summary of the evidence is that “a single intravenous dose of ketamine produced ‘robust and rapid antidepressant effects’ within a couple of hours.” That sort of vague endorsement of benefits doesn’t give readers or listeners an accurate sense of how meager the trial evidence of benefits really is.

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

Not Satisfactory

Although there is a brief mention of possible harms, including abuse and hallucinations, the soft warnings in the story are undercut by statements such as, “ketamine’s safety record is so good that it’s often the painkiller of choice for children who arrive in the emergency room with a broken bone.” Again, readers and listeners are given the impression that the drug has been scrutinized far more carefully that it actually has.

There is a final cautionary note from a proponent of ketamine treatment of depression that wider use could mean “something bad will happen to a depressed patient”. However, this risk is cast not as a hazard inherent in the drug, but as worry that a careless doctor will tarnish the drug’s good name.

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

Not Satisfactory

The story fails to mention that the “landmark” study pointing to antidepressant effects of ketamine included only 18 patients and lasted only two weeks. What’s more, the patients were carefully selected at an inpatient psychiatric facility… and more potential participants were excluded or declined than ended up participating. This study and some others specifically warn against trying to extrapolate the results in this sort of narrowly-selected patient group to the general sort of person living with depression in the community. This story takes the leap that researchers warned against.

People with depression so bad they think about suicide are in desperate need of effective treatments, but this story gives the impression that there is a substantial body of scientific evidence to support using ketamine, when actually there are only a few tiny, short-term trials involving very unusual patients, along with an undefined mass of unscientific anecdotes.

The story could have given readers and listeners a better sense of how these doctors and patients are taking a blind leap into the unknown, as understandable as that desperate action may be.

Does the story commit disease-mongering?

Satisfactory

This ruling is a close call that we’ll ultimately give the benefit of the doubt on. Clearly the gist of the story is that ketamine is something being offered to people with depression so bad that they are thinking about suicide despite having tried all approved treatments. But the key trial highlighted in the story included this strong cautionary note: “Although these results are provocative, they may not be generalizable to all populations with depression. The subjects in this study were a refractory subgroup who were relatively late in their course of illness, and as such, their neurobiology and pharmacological responses may be different from those with a less severe or shorter course of illness.” By featuring a man living out in the community (as opposed to a psychiatric facility where the drug was administered in the trial), it’s arguable that this story does just what the researchers warned against.

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

Satisfactory

The story relies almost entirely on a single passionate advocate and a single compelling patient. The story would have been strengthened and balanced by an interview with someone with a contrary opinion. We’ll give the story a pass for featuring a skeptical blog quote from the director of the National Institute of Mental Health. But the story could have done more to highlight experts who are critical of the use of ketamine and feature patients who didn’t respond to the drug.

Does the story compare the new approach with existing alternatives?

Not Satisfactory

This story seems to have two different standards for summarizing study evidence. Even as the story highlights the potential benefits and minimizes harms of ketamine, it dismisses conventional treatments saying a major study concluded “current antidepressants really aren’t much better than a placebo.” For the severe depression mentioned in the story, there is evidence that antidepressants are quite a bit better than placebo.

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

Satisfactory

The story reports that ketamine is not approved for treatment of depression, but it is widely used as an anesthetic.

Does the story establish the true novelty of the approach?

Satisfactory

The story notes that the key study it mentions was published almost a decade ago. And it suggests that the recent surge in clinics that are offering this treatment makes the story worthy of coverage now.

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

Satisfactory

The story goes beyond any news release.

Total Score: 6 of 10 Satisfactory

Comments (5)

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Stephen Hyde

September 30, 2015 at 8:11 pm

While I agree with your comments on the article in general I do take issue with your comment that there are just ‘a few tiny short-term trials’ that attest to ketamine’s effectiveness in hard to treat depressive illnesses. In fact I’ve summarised the many trials into the use of ketamine over the past 15 years in “Ketamine and Depression” which you can explore at the Xlibris online bookstore. Currently in the US alone there are over 50 trials recruiting, chiefly looking at the use ketamine in depression but also exploring its use in OCD, PTSD and eating disorders. Given that ketamine is out of patent most trials are by necessity small as the pharmaceutical companies have no incentive to invest, but there is an emerging consensus from studies both in psychiatry and pain medicine that ketamine, as part of a comprehensive treatment plan, can a safe effective and, depending on the route of administration, very affordable treatment option.
Dr Stephen Hyde – FRANZCP.

Reply

    susan_molchan@verizon.net

    October 1, 2015 at 11:19 am

    Thanks to Dr. Hyde for his comments. As the psychiatrist among the reviewers, I agree completely that ketamine is looking like a safe and effective treatment option. I wasn’t aware of the number of trials done, as we can only access those in PubMed & don’t do an exhaustive review for these reviews. Small trials have their limitations, and given the original NIMH study almost 10 years ago, it’s unfortunate a large definitive trial funded by the NIMH hasn’t long been completed. Drug companies are working on ketamine analogues that they can patent, and that hopefully will have fewer side effects and perhaps longer action. But they will be very expensive.

    Reply

      Stephen Hyde

      October 2, 2015 at 2:15 am

      I completely agree Susan, and the other issue with the analogues is that there will be no long term data to establish safety whereas ketamine, which has been used for over 50 years as an anaesthetic and in pain medicine for the past 20 years, is clearly safe when taken in the relatively low doses used in the trials. Varun Jaitly in England has been treating patients with chronic severe pain with daily sublingual ketamine for up to 15 years now [some taking it for all of this time] and he has not seen any ill-effects flowing from this. So ketamine is the ‘devil we know’ and there is no reason that patients with treatment-resistant conditions should not be given the facts and the opportunity to try it. It is also important to remember that in the past 50 years there have been no reports of dependence or addiction arising from the medical use of ketamine, although some who take regular very high doses ‘recreationally,’ can have major physical and psychological problems.

    Andrew Holtz

    October 1, 2015 at 2:19 pm

    As the first reviewer of this story, I stand by our characterization of the trial evidence. A new Cochrane review, “Ketamine and other glutamate receptor modulators for depression in adults”, found only 9 trials of ketamine worthy of inclusion. None lasted more than a few weeks. The total number of participants in all the trials combined was only 56. What’s more, the Cochrane reviewers rated all of the trials as low quality. See http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011612.pub2/abstract
    Our review doesn’t say ketamine is not effective. There may even be a consensus forming among experts that ketamine has a place in comprehensive treatment of depression. But the fact remains that the published evidence on the question is, at the moment, based on a few, tiny, short-term trials.

    Reply

Rupert McShane

October 8, 2015 at 3:08 am

I agree with all that has been said so far. Of course decent longer trials in more generalisable populations are required. It is important that clinicians using ketamine publish what they are doing so that the experience of the various possible alternative maintenance strategies can be referred to in grant applications for the necessary trials. It will also help in establishing the routes, dose ranges and frequency to be tested, and importantly in providing experience about the extent of tolerance and tachyphylaxis. The issue about ‘harms’ is an interesting one. Here is a licensed drug which is on the WHO essential drugs list and is clearly safe acutely. There is some published experience of long term use but not much. If there are are few/no yellow card reports of problems when used in the medical context, then there will still be ‘no evidence’ on harms. Publication of long term use by anaesthetists is important – not least because the doses used are likely to be much higher than those used in depression. But how many dogs have to not bark in the night before we can be sure there are no dogs? Rupert McShane, Oxford

Reply