“Flimsy Evidence” for Esketamine as Depression Treatment

A new article documents the “flimsy evidence” behind the recent FDA approval of esketamine for the treatment of depression.


An editorial in BMJ documents the “flimsy evidence” behind the recent decision by the US Food and Drug Administration (FDA) to approve esketamine for the treatment of depression. The article suggests that the promotion of esketamine is “putting drug company interests over the public good.” The article is written by Joanna Moncrieff, a practicing psychiatrist and founder of the Critical Psychiatry Network, and Mark Horowitz, a researcher in psychiatry at University College London.

“The scientific community should instead be calling on the European Medicines Agency to resist the proposal to unleash another chemical on the unsuspecting public that has unproven benefits and untested harms.”

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Esketamine is a nasal spray formulation of ketamine. Ketamine is one of a number of psychoactive drugs that were synthesized or popularized in the 1960s and often used recreationally. Some theorists believe that hallucinogenic substances like ketamine can create “an altered state of consciousness” in the patient, which might enable psychotherapy to have a greater effect than usual. That is, ketamine could allow a person to be more receptive to the actual healing of psychotherapy.

In current psychiatric practice, however, esketamine is not used in this fashion. Instead, the assumption is that esketamine without any other factors acts to reduce depressive symptoms and provide healing. However, according to Moncrieff and Horowitz, the evidence for such an effect is minimal. They report that of the three initial trials of the drug submitted to the FDA, only one was positive. Two trials showed no significant effect. Even the positive study found esketamine to be only slightly better than a placebo.

Moncrieff and Horowitz write that the most likely explanation for that slight positive effect is that, like alcohol, the drug has the potential to mask negative feelings and temporarily induce positive experiences.

Additionally, there is very little scientific knowledge about the long-term effects of the drug. However, Moncrieff and Horowitz state that observational studies of party drug use show bladder damage and depressogenic effects from long-term use of ketamine and similar drugs.

The researchers conclude that “Leaving this crucial research until after the drug is licensed, as the FDA has done in the United States […] puts the public at risk and sets depressed patients up as unwitting guinea pigs in a huge and unregulated pharmaceutical experiment.”



Moncrieff, J., & Horowitz, M. (2019). Esketamine for treatment-resistant depression. BMJ, 366. DOI: https://doi.org/10.1136/bmj.l5572 (Link)


  1. May I point out again that l-glutamine antagonizes these ketamine and phencyclidine(PCP) class drugs, as they antagonize its metabolite, glutamate. Since glutamine is comparatively cheap in bulk and can’t be patented, your friends in Big Pharma will never consider marketing it, themselves. It’s on the market as a bulk powder for the hyper-athletic, because it helps supply oxygen for their muscles. As a side note, it also reduces the desire to drink alcoholic beverages.

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  2. Once again all this goes to show that the FDA is not working to protect the people of the United States but to protect the profit interests of the large drug companies that are running our country today.

    At least someone is finally speaking out against the damned stuff and calling the FDA out on their flagrant decision to put American citizens at risk.

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  3. Good Morning Mr. Simmons,

    At multiple points throughout your article you state Ketamine was tested or that Ketamine was approved by the FDA. The BMJ article clearly states that this was Esketamine which had the outcomes similar to placebo. While you may think that enantiomers would have similar effects, they do not. Take the drug which is constantly harped on for its differences of effect when using the Left or Right handed version, Thalidomide. One version helps with nausea during pregnancy, the other causes children to be born without limbs. Enantiomeric effects are important to understand, and comparing Racemic Ketamine with the left-handed enantiomer Esketamine is being intellectually dishonest. Stigma in mental health and emerging therapies is already difficult enough to manage. Please do not contribute to the issue. I believe you may have just been mistaken. I hope a swift correction or clarification is made.


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  4. Sunbelt Wellness, as you well know, ketamine (as distinct from eskatamine) is increasingly being used as a treatment for depression and PTSD, among other things. If you have an issue with the study itself I suggest you take that up with the authors.

    Reporting on new scientific findings should never be silenced because you think those findings might be stigmatizing; that’s censorship. Science is science; we may not always like what it tells us, but it gives us more information with which to make decisions.

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    • Ms. Spencer,
      I believe my original message may have been misconstrued. The study is linked below the article and specifically says Esketamine (Not Ketamine). The author of this article then wrote in Ketamine where the original authors had Esketamine. That is not silencing. This author has blatantly edited the original findings and replaced each mention of Esketamine with Ketamine. As we stated above these are not the same medication. Enantiomers have massive effects on drug delivery and targeting. I do not believe the author did this on purpose but possibly thought they were the same substance. Misinformation is damaging to persons seeking treatment. We are hoping to bring light to this so that education/research/ethics are again at the forefront of medical literature and commentary.

      Thank you

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  5. I’m getting tired of the line that “there is very little scientific knowledge about the long-term effects of the drug”.

    There’s plenty of knowledge gathered here in Bristol / UK where we had a recreational ketamine epidemic in the late 1990s and 2000s. Presumably, a sizeable share those taking ketamine were self-medicating.


    “At the age of 23, Nancy had died slowly over seven years, her body trashed by a steady diet of ketamine.”

    Bristol’s BRI hospital reportedly performed lots of bladder surgery during that time. I’m amazed nobody in the scientific community seems to have reached out to BRI, or to Bristol’s drug councelling services.

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