Ketamine has been shown to be efficacious for the treatment of depression, specifically
among individuals who do not respond to first-line treatments. There is still, however, a lack of clarity
surrounding the clinical features and response periods across samples that respond to ketamine. This
paper systematically reviews published randomized controlled trials that investigate ketamine as an antidepressant
intervention in both unipolar and bipolar depression to determine the specific clinical features
of the samples across different efficacy periods. Moreover, similarities and differences in clinical characteristics
associated with acute versus longer-term drug response are discussed. Similarities across all
samples suggest that the population that responds to ketamine’s antidepressant effect has experienced
chronic, long-term depression, approaching ketamine treatment as a “last resort”. Moreover, differences
between these groups suggest future research to investigate the potential of stronger efficacy towards
depression in the context of bipolar disorder compared to major depression, and in participants who undergo
antidepressant washout before ketamine administration. From these findings, suggestions for the
future direction of ketamine research for depression are formed.
Keywords: Ketamine, Depression, Bipolar disorder, Clinical characteristics, Pharmacogenetics, Glutamatergic dysfunction.
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