A number of drugs have been studied recently for the management of treatment-resistant depression. One is ketamine. Ketamine has been used as an anaesthetic and a painkiller for many years. It is available as arketamine (R-ketamine) and esketamine (S-ketamine). A formula containing equal amounts of R-ketamine and S-ketamine is called racemic ketamine.

Before discussing the present investigation, let me briefly describe ketamine and treatment-resistant depression. As noted earlier, some people with depression, despite trying different first-line medications (e.g., sertraline, fluoxetine), still struggle with depressive symptoms that significantly interfere with their functioning, well-being, and happiness. For instance, a large study found that one in three depressed patients failed to achieve remission after trying multiple antidepressant treatments.


Aside from being an aesthetic and a painkiller, ketamine is also a dissociative drug, meaning it can cause sensations of disconnection from reality (e.g., sense of floating). Indeed, because of its dissociative and hallucinogenic effects, ketamine has been used recreationally for decades.

More recently, ketamine has been used clinically and investigated for the treatment of a variety of symptoms and mental health conditions, such as anxiety, post-traumatic stress disorder (PTSD), and particularly treatment-resistant depression.

Commonly prescribed antidepressants, like selective serotonin reuptake inhibitors (SSRIs), have benefited many patients. Nevertheless, partial response or no response to these antidepressants is common. What can be done in these cases? Perhaps ketamine could help.

The authors used terms related to ketamine and depression to search Pubmed and Google Scholar for randomized placebo-controlled human studies. The final results included a list of 21 studies.

To compare effect sizes, mean differences were calculated. The outcomes were converted to Hedge’s g —a measure of effect size, or the strength of the relationship between the variables under consideration.

The results were promising: Specifically, a random-effects meta-analysis showed “large and significant effects for all formulations of ketamine administration.”

The following pooled effect sizes were found for different methods of administration:

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