Esketamine initiation, compared with oral antidepressant monotherapy, was associated with a 26% lower risk of all-cause mortality over two years among adults aged 18–74 with cancer-related depression, according to a target trial emulation using electronic health records. After propensity score matching of 1,751 patients per group, esketamine also corresponded to lower risks of emergency room visits, intensive care unit visits, ischemic stroke, and psychotherapy utilization. Safety outcomes were generally comparable between groups. The associations were more pronounced in older patients. These real-world findings support esketamine as a potential therapeutic option for managing cancer-related depression.
Among adults with treatment-resistant depression, repetitive transcranial magnetic stimulation (rTMS) was associated with fewer medical complications than esketamine over the first year, including lower risks of hospitalization, arrhythmia, and any injury. Suicide-related outcomes were broadly comparable overall, though esketamine showed a protective advantage during the 30-90-day interval and among patients aged 45-65 years. The analysis used target trial emulation with propensity score matching on 50 covariates, drawing on electronic health records of 1,690 matched patients per treatment group. The findings suggest rTMS has a more favorable overall medical safety profile, while suicide risks were similar except for specific subgroups and time periods.