Relief Pathways: IV Ketamine vs Esketamine

Relief Pathways: IV Ketamine vs Esketamine

While the usage of ketamine in clinical medicine has been in existence for fifty years, its breakthrough application for treatment-resistant depression is novel. So, what is new? Head-to-head formulation research studies comparing intravenous racemic ketamine versus intranasal esketamine (Spravato) are now emerging. We are excited to break down three findings from the first systematic review and meta-analysis of the two treatments, in a National Institute of Health (NIH) funded study. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis is now available online and scheduled for print publication in January 2021.

First synthesized in 1962, ketamine was only FDA approved as an anesthetic in 1970. The original formulation of ketamine is racemic, which means it has an equal portion of ‘left-handed’ and ‘right-handed’ molecules. The two forms are referred to as S-ketamine and R-ketamine. After isolating just the S-ketamine molecule, Jansen Pharmaceuticals gained FDA approval for their nasal spray esketamine (Spravato) for treatment-resistant depression.

Racemic ketamine vs Esketamine

In both unipolar and bipolar depression treatment, intravenous ketamine is considered superior to intranasal s-ketamine. Intravenous ketamine provided a “more significant overall response and remission rates, as well as lower drop-outs due to adverse effects”.

Racemic ketamine for depression

A meta-analysis is a type of research that combines the results of multiple, published scientific studies to help develop the best educated and data-driven conclusions. This particular study further solidifies racemic ketamine’s role in rapid-acting treatment for both unipolar and bipolar depression.

We look forward to continued research on ketamine. Our mission at Alchemy is to provide safe and effective treatments for our patients living with mood disorders and pain. We are committed to staying up-to-date on the latesat research and information for optimal responses. Interested in the full article? Access it here.


Bahji A, Vazquez GH, Zarate CA Jr. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021 Jan 1;278:542-555. doi: 10.1016/j.jad.2020.09.071. Epub 2020 Sep 23. Erratum in: J Affect Disord. 2020 Nov 20;: PMID: 33022440; PMCID: PMC7704936.

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