Effects of ketamine on metabolic parameters in depressive disorders: A systematic review

Background: Persons with Major Depressive Disorder (MDD), notably treatment-resistant depression (TRD), are differentially affected by type 2 diabetes mellitus and associated morbidity. Ketamine is highly efficacious in the treatment of adults living with MDD, notably TRD. Herein, we sought to determine the effect of ketamine on metabolic parameters in animal stress paradigms and human studies. Methods: We performed a comprehensive search on PubMed, OVID, and Scopus databases for primary research articles from inception to May 5, 2024. Study screening and data extraction were performed by two reviewers (S. W. and G.H.L.). Both preclinical and clinical studies were included in this review. Results: Results from the preclinical studies indicate that in experimental diabetic conditions, ketamine does not disrupt glucose-insulin homeostasis. Within adults with MDD, ketamine is associated with GLUT3 transporter upregulation and differentially affects metabolomic signatures. In adults with TRD, ketamine induces increased brain glucose uptake in the prefrontal cortex. Available evidence suggests that ketamine does not adversely affect metabolic parameters. Limitations: There are a paucity of clinical studies evaluating the effects of ketamine on glucose-insulin homeostasis in adults with MDD. Conclusions: Our results indicate that ketamine is not associated with significant and/or persistent disruptions in metabolic parameters. Available evidence indicates that ketamine does not adversely affect glucose-insulin homeostasis. These results underscore ketamine's efficacy and safety as an antidepressant treatment that is not associated with metabolic disturbances commonly reported with current augmentation therapies.