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.
Rasmussen KG. Ketamine for Posttraumatic Stress Disorder. JAMA Psychiatry. 2015;72(1):94-95. doi:10.1001/jamapsychiatry.2014.1621