To the Editor In their presentation of guidelines for the use of ketamine in mood disorders, Sanacora et al1 rightly state that ketamine is not standard treatment in psychiatry but then inexplicably refer to 0.5 mg/kg intravenously over 40 minutes as the “standard” dose. How can there be a standard dose for a nonstandard treatment? A brief review of the history of this dosing method is instructive. The first to use this dosing format for depression was Berman et al,2 who did not provide any rationale. They did cite Krystal et al,3 who used 0.5 mg/kg intravenously over 40 minutes for studies of ketamine in normal volunteers. In turn, that group cited, as a basis for this dosage and infusion rate, the classic studies of Domino et al4 and Corssen and Domino.5 However, those investigators infused ketamine over a few seconds to 1 minute. Thus, it would seem that the now familiar 0.5 mg/kg over 40 minutes is arbitrary, without any pharmacodynamic or pharmacokinetic rationale.
Rasmussen KG. Ketamine for the Treatment of Depression. JAMA Psychiatry. 2017;74(9):970–971. doi:10.1001/jamapsychiatry.2017.1773