Researchers from the National Institutes of Health have published a review article focused on ketamine’s effects in patients with depression, particularly in relation to gamma oscillations and long-term potentiation, both putative markers of synaptic potentiation. The review was published in Pharmacology, Biochemistry, and Behavior.

Acute ketamine administration is associated with pyramidal cell disinhibition downstream of NMDA receptor antagonism, which can lead to changes in gamma oscillations. Acute ketamine treatment has also been shown to reduce lower-frequency delta and theta oscillations.

Administration of ketamine at therapeutic and subanesthetic levels has also been shown to result in substantial increases in gamma oscillations and gamma power measures. Based on current data, the authors indicate that delayed gamma power estimates may be a potential biomarker of both ketamine response and synaptic potentiation, thus differentiating between responders and nonresponders.

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Research has yet to determine the underlying mechanisms between acute gamma oscillations and antidepressant response in specific types of mood disorders. Some research findings, the authors wrote, suggest a potentially optimal level of gamma power that is essential for mediating the postadministration antidepressant response associated with ketamine.

In studies of ketamine and its association with long-term potentiation, the upregulation of long-term potentiation with ketamine may be a crucial mechanism that mediates the drug’s antidepressant effects. A study included in the review found no evidence of an association between changes in event-related potential amplitude and antidepressant response with ketamine.

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According to the authors, further research is required to determine whether measures of long-term potentiation in both the primary visual and auditory cortices could represent biomarkers of an antidepressant response mediated by ketamine. Furthermore, research in these fields could provide further knowledge on ketamine response and “ultimately help develop next-generation antidepressants by providing a more complete, mechanistic understanding of ketamine’s antidepressant effects,” the study authors wrote.


Gilbert JR, Zarate CA Jr. Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: gamma power and long-term potentiation [published online January 17, 2020]. Pharmacol Biochem Behav. doi:10.1016/j.pbb.2020.172856