In Reply Rasmussen has correctly pointed out that the 0.5-mg/kg dose of racemic ketamine hydrochloride used in most published reports to date was not arrived at through extensive preclinical studies or strong experimental therapeutic rationale. In fact, the 0.5-mg/kg dose provided over a 40-minute intravenous infusion implemented in the original Berman et al1 study was adopted from a previous dosing strategy devised by Krystal et al2 as a means of assessing the acute psychotomimetic, perceptual, and cognitive effects of ketamine as a potential model of psychosis. The 0.5-mg/kg infusion over 40 minutes was chosen specifically because it resulted in clearly observable psychoactive effects but still allowed the patients to remain lucid enough to complete a battery of cognitive assessments, not because of any special belief about the optimal antidepressant dosing. We referred to this as the “standard dose” in the consensus statement3 solely because it was used in most published reports. Because this was the only dose with replicated findings across several clinical laboratories, it was the only dose that we felt comfortable evaluating at the present time. We did not mean to imply that this is the optimal or correct dose to be used for the treatment of mood disorders.
Gerard Sanacora. Ketamine for the Treatment of Depression—Reply. JAMA Psychiatry. 2017;74(9):971–972. doi:10.1001/jamapsychiatry.2017.1776