To the Editor The Feder et al1 study published in JAMA Psychiatry found that a single infusion of ketamine was more efficacious in reducing symptoms of posttraumatic stress disorder than midazolam. However, midazolam was rather successful in its own right, being associated with approximately 50% reductions in posttraumatic stress disorder severity scores at 24 hours postinfusion. A similarly designed ketamine vs midazolam study in depression from the same research group2 found midazolam was associated with a 28% response rate at 24 hours postinfusion, a rather substantial improvement, although ketamine was better. In both studies, midazolam was referred to as psychoactive placebo while the effects of ketamine were couched as involving the N-methyl-D-aspartate receptor complex. A more circumspect consideration of the data leaves the investigators with several possible explanations: (1) ketamine effects are due to inherent neurobiological actions and those of midazolam mere placebo; (2) midazolam and ketamine effects are both due to inherent neurobiologic actions; and (3) both ketamine and midazolam effects are related to expectational phenomena (ie, placebo effect) and ketamine is a better placebo than midazolam. There may be both placebo and an inherent neurobiologic mechanism to explain ketamine effects. However, the same could be true of midazolam.