Neurobiological biomarkers of response to ketamine.
Bashkim Kadriu, Elizabeth D Ballard, Ioline D Henter, Stephen Murata, Nimesha Gerlus, Carlos A Zarate
Advances in pharmacology (San Diego, Calif.) January 1, 2020 Peer reviewed DOI: 10.1016/bs.apha.2020.05.003 via PubMed
Summary
The rapid-acting antidepressant ketamine has changed the approach to treating treatment-resistant depression by highlighting the importance of identifying biomarkers for response. This chapter reviews various biomarkers, including those related to neuroimaging, sleep, and genetic factors, which could help identify patients more likely to benefit from ketamine therapy. However, while some biomarkers show promise in understanding ketamine's effects, none are currently ready for clinical application.
Study at a glance
| Key finding | None of the biomarkers reviewed are ready for clinical use. |
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Abstract
As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response support a growing emphasis on early identification, which would allow clinicians to identify biologically enriched subgroups with treatment-resistant depression who are more likely to benefit from ketamine therapy. This chapter presents a broad overview of a range of translational biomarkers, including those drawn from imaging and electrophysiological studies, sleep and circadian rhythms, and HPA axis/endocrine function as well as metabolic, immune, (epi)genetic, and neurotrophic biomarkers related to ketamine response. Ketamine's unique, rapid-acting properties may serve as a model to explore a whole new class of novel rapid-acting treatments with the potential to revolutionize drug development and discovery. However, it should be noted that although several of the biomarkers reviewed here provide promising insights into ketamine's mechanism of action, most studies have focused on acute rather than longer-term antidepressant effects and, at present, none of the biomarkers are ready for clinical use.