Background

Ketamine is a racemic mixture, consisting of equal amounts of its two enantiomers. It has been recognized for its rapid-acting antidepressant effects and some data also suggest safety and efficacy in treating anxiety disorders. However, it is unclear which ketamine formulation has the highest efficacy and most tolerable safety profile, in treating these conditions.

Aim

This systematic review aimed to assess whether there is any clinical evidence favoring the use of either of the two ketamine enantiomers over the racemat, in the treatment of depressive or anxiety disorders.

Methods

PubMed, Cochrane, PsycINFO and Scopus databases were searched for relevant studies published from their respective inception to April 19, 2021. Reference lists of topical reviews were also hand-searched for potentially relevant articles.

Result

Five trials with a total of 140 subjects were included. Of these, three studies investigated the effects of differing ketamine formulations on treatment-resistant major depressive disorder and two studies investigated the subjective effects on healthy volunteers. All three ketamine formulations show promise in treating depressive disorders, but it is unclear which formulation has the highest efficacy.

Conclusions

There is too little data comparing the efficacy of the different ketamine formulations to suggest superiority of any of the two ketamine enantiomers over the racemate. Large scale, head-to-head studies are warranted.