A systematic review of 17 rodent studies found that ketamine's effects on brain-derived neurotrophic factor (BDNF) depend on treatment duration, species, and sex. Sub-chronic and chronic ketamine treatment decreased BDNF or had no effect in rats, and decreased BDNF in mice. Acute ketamine treatment commonly increased BDNF. One study reported inconsistent BDNF changes between male and female rats. Due to high methodological variability, there is currently no standardized method for using ketamine as a rodent model of schizophrenia.
A systematic review of 38 randomized controlled trials found compelling evidence that ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657) are effective for treatment-resistant depression, though results for the latter three were each based on a single study. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results, while riluzole and 7-chlorokynurenic acid were mostly comparable to placebo. High heterogeneity among trials prevented determining the difference between statistical and clinical significance. Ketamine appears efficacious, but optimal dosage, duration, and intervals remain unclear.