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Data-mining expedition reports striking ketamine gold, but readers shouldn’t rush to judgment

First large-scale population analysis reinforces ketamine's reputation as antidepressant

Our Review Summary

In this study of the effect of the anesthetic drug ketamine on depression, researchers at University of California – San Diego data-mined the FDA Adverse Effect Reporting System database for information on ketamine use for pain relief. Their analysis found an association between ketamine and reduced incidence of depression. However, the absence of depression the researchers found in 41,000 people (out of 8 million entries in the database) taking ketamine for pain relief in no way proves ketamine is responsible for the lack of depression. The release and the study it’s based on stand on a very shaky foundation.

The release’s only nod to caution about the findings is an acknowledgement that the effect of ketamine on depression could be due to an “unidentified” factor. But it does not mention the problems with this retrospective, data-mining study, the main one being that the absence of a symptom (depression) does not equate to the drug alleviating the symptom. No mention is made of the fact that the data were not collected for the purpose for which the researchers used them or the fact that there are no medical histories attached to the subjects included in the study.


Why This Matters

According to the World Health Organization, more than 300 million people experience depression worldwide. The suffering due to depression can be severe, and affect families, co-workers and friends of the person with the diagnosis. Most anti-depression medications take weeks if not months to reach full effect, and many patients quit taking the drugs before they reach full effectiveness. Patients with acute depression or suicidal intentions need drugs that will work more rapidly. Because anti-depression medications do not work for everyone, an effective intervention that might work quickly would be beneficial.

There’s a lot of better-designed research underway on ketamine and its safety and usefulness in treating depression. Readers would be best served waiting for stronger evidence to emerge before drawing conclusions.


Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

The release does not specify cost, but says ketamine is “relatively inexpensive and is covered by most health insurance plans if three other antidepressants fail.” If prescribed it is done so “off-label” since ketamine is not FDA approved for depression, and thus not covered by health insurance. At least one ketamine treatment center says the drug is not covered by insurance.

The release also doesn’t specify which ketamine formulation it assessed. When given by infusion, which is how depression is treated clinically with the drug, it can cost several hundred dollars per treatment.

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

Not Satisfactory

The release strongly suggests ketamine is beneficial for depression, but gives almost no evidence. It states that compared to other patients in the database, ketamine users showed a 50 percent reduction in depression, but no absolute numbers of people aided by the drug were provided. The absence of depression as a side effect is a novel but invalid way of defining effectiveness.

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

The release does not mention any harms from taking ketamine. A British Journal of Clinical Pharmacology study of ketamine for chronic pain devoted a lengthy discussion to side effects from clinical ketamine use, dividing them into central nervous system (CNS)-related, cardiovascular and hepatic (liver).

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The release does not clearly explain the limitations of a retrospective, data-mining study and how it differs from conclusive evidence that can be obtained in a randomized, controlled trial. While certainly some information can be garnered from this type of study, and the paper itself indicates that clinical studies would be necessary to establish these findings, the release does not include this important point. Perhaps the release’s biggest weakness is the omission that the data were collected for other purposes (adverse event reporting) and that patient histories are missing.

The study is unusual in that it assumes that the lack of mention of depression is evidence of improvement in depression, and that is a stretch. The analysis also found the same so-called “anti-depressant” effect in other drugs that had no obvious mechanism of action: an antibiotic, an anti-inflammatory, and a wrinkle treatment.

The release does give a nod to the fact that other factors may be at play with this statement: “Abagyan says it’s still possible, though unlikely, the effect could be due to a still unidentified confounding factor.” However, that statement inappropriately downplays the many limitations of this association study.

Does the news release commit disease-mongering?

Not Applicable

There is no disease mongering here, but the release doesn’t provide any context about depression. We’ll rate it N/A.

Does the news release identify funding sources & disclose conflicts of interest?


The release names the funder, not in the release text itself but on the EurekaAlert! website which hosts the news release.

Does the news release compare the new approach with existing alternatives?


The release notes that depression is currently treated with “five classes of antidepressants, most commonly serotonin uptake inhibitors.”

The release could also have included psychotherapy and other common non-pharmaceutical therapies for depression.

Does the news release establish the availability of the treatment/test/product/procedure?

Not Satisfactory

The release does not address availability or how many physicians currently prescribe ketamine for depression.

Does the news release establish the true novelty of the approach?

Not Satisfactory

The release refers often to this study being the largest of its kind and the first “large-scale” study of ketamine for depression. The second sentence might lead some people to believe that this analysis is a large clinical trial — which it is not.

The research is novel only in its approach to claiming a benefit where there is no clear-cut relationship.

Ketamine has been tested in several small studies and research is on-going.

The release establishes some novelty with this statement: “While most researchers and regulators monitor the FAERS database for increased incidences of symptoms in order to spot potentially harmful drug side effects, we were looking for the opposite — lack of a symptom.” But the fact remains, this is questionable science.

Total Score: 3 of 9 Satisfactory


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