Implications for clinical translation
treatment-resistant depression
ADVERSE EFFECTS
Strengths of the study include the large sample and the use of low-cost, generic ketamine, which is globally available as a result of being on the World Health Organization (WHO) Essential Medicines List as an anaesthetic. Treatment was given by the relatively simple subcutaneous injection method, greatly increasing its clinical translation potential compared with prior parenteral approaches such as a 40 min intravenous infusion, and this treatment approach may be as acceptable to patients as oral or intranasal routes. There was comprehensive evaluation of safety and, to our knowledge, this is the only study using structured assessments of cumulative and between-session effects, as well as acute and overall course effects, and using a tool specifically designed to evaluate adverse effects of ketamine (KSET).This study provides evidence that racemic ketamine, given by subcutaneous injection at adequate doses, is safe and efficacious in the therapy of treatment-resistant depression over a 4-week treatment course. Benefits attenuate after treatment cessation for most patients, supporting prior evidence that ketamine should be considered as a longer-term treatment. Future research questions include head-to-head comparisons of racemic, R- and S-ketamine, comparisons of routes of administration and testing of treatment strategies to extend benefits and reduce relapse rates.