Ketamine use in relation to depressive symptoms among high school seniors

Background and Objectives Ketamine is efficacious in treating treatment‐resistant depression in medical settings and the drug was approved for such use by the US Federal Drug Administration in 2019. However, little is known about how use outside of medical settings relates to depression. We determined whether recreational ketamine use, relative to the use of other drugs, is related to the current experience of depression among adolescents. Methods We examined data from the 2016 to 2019 Monitoring the Future nationally representative survey of high school seniors in the United States (N = 15,673). We determined how past‐year drug use and frequency of past‐year drug use were associated with students reporting a high level of current depressive symptoms relative to other students. Results Ketamine use was associated with highest risk for a high level of depression (aPR = 1.55, 95% confidence interval [CI]: 1.24–1.94), followed by use of cannabis (aPR = 1.29, 95% CI: 1.19–1.39), and nonmedical use of tranquilizers (aPR = 1.22, 95% CI: 1.04–1.44) and amphetamine (aPR = 1.17, 95% CI: 1.01–1.34). Alcohol use was associated with decreased risk (aPR = 0.92, 95% CI: 0.85–0.99). With respect to frequency of past‐year use, more frequent use of ketamine and cannabis was associated with increased risk for a high level of depression in a dose‐response‐like manner, with past‐year use of ketamine and cannabis ≥10 times associated with increased risk for depression by 70% and 40%, respectively. Discussion and Conclusions Past‐year recreational ketamine use is a risk factor for reporting current depression than most other drugs. Scientific Significance This was the first study to compare the risk of use of various drugs in relation to depression.