I recently had a physician call me because he was setting up an esketamine clinic and wanted referrals. I asked him to get me the research on esketamine and never heard back. I suspect that is because there is very little he could have produced. Eketamine is the nasal spray formulation of Ketamine. Ketamine is a psychoactive drug typically used as an anesthetic for surgery and to help with pain during some procedures. Esketamine is used for “treatment resistant depression”. Read that again….”treatment resistant”. In other words, the treatment you have been on, most likely an SSRI, is not working so we are going to add this to the arsenal. Now that would be bad enough if we stopped right there. The problem is that, like with all depression and anxiety medications, we struggle to find support for the effectiveness of this drug.

Joanna Moncrieff, a practicing psychiatrist and founder of the Critical Psychiatry Network, and Mark Horowitz, a researcher in psychiatry at University College London state that,  “Like other antidepressants, it is suggested to work by acting on some hypothetical neural mechanism of depression, yet it is more likely that its characteristic mind-altering effects simply mask or override depressed feelings, in the same way that alcohol can temporarily ‘drown your sorrows’”. Ketamine has been used recreationally due to its hallucinogenic and dissociative effects. It is likely that esketamine, in the dosage prescribed by your physician, is simply hiding the depressed feelings temporarily and certainly keeping you from dealing with the underlying issues.

I stated earlier that we struggle to find support for the effectiveness of depression and anxiety medications. According to researchers Irving Kirsch , Brett J Deacon, Tania B Huedo-Medina, Alan Scoboria, Thomas J Moore, and Blair T Johnson, “Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication”. Plainly stated, this means that the effectiveness of antidepressants is primarily attributable to placebo. The placebo effect is a beneficial response to a harmless pill or substance that has no therapeutic effect. Placebo is used as a control when drug testing takes place. Essentially a placebo is used to determine whether improvement of a symptom is due to the drug itself or the BELIEF that the drug produced the effect.

Kirsch also points out in a 2014 article titled, “Antidepressants and the Placebo Effect” that the theory of “chemical imbalance” has primarily been based on the pharmaceutical industry's misleading statements of antidepressant effectiveness. This should be troubling to anyone seeking pharmaceutical help. Kirsch is not alone in his findings though he has taken the brunt of negative reaction by the medical and pharmaceutical community. Kirsch states, “The results of our analyses have since been replicated repeatedly (Fountoulakis & Möller, 2011; Fournier et al., 2010; NICE, 2004; Turner et al., 2008). Some of the replications used our data; others analyzed different sets of clinical trials. The FDA even did its own meta-analysis on all of the antidepressants that they have approved (Khin et al., 2011)”. The results of these analyses confirm Kirsch’s studies. Given the significant side-effects of these drugs it seems that adding another poorly researched medication (esketamine) to an already questionable drug is irresponsible at best.

The bottom line is that you as the consumer should begin to take your mental well-being seriously. That means seeking a reason for the depressed or anxious feelings you have instead of relying on pharmaceutical advice founded in faulty studies that assume a biological determinant for your problem. A competent therapist can help with this.

Works Cited:

Kirsch I. (2014). Antidepressants and the Placebo Effect. Zeitschrift fur Psychologie, 222(3), 128–134. doi:10.1027/2151-2604/a000176

Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (2008) Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Med 5(2): e45. https://doi.org/10.1371/journal.pmed.0050045

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