Ketamine has been safely used for induction and maintenance of anesthesia for decades and
more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity
antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on
dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have
been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman,
Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot,
Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently
three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow
intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a
clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25
patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et
al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine
infusions prolongs the duration of improvement.
The investigators believe that the data presented above allows us to provide ketamine
treatment here in the Sheba Medical Center for TRD patients.