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