New Ketamine Data

As was discussed at length in December’s NeuroPerspective, the quest for a rapid-acting anti-depressant (RAAD) continues to be one of the most closely watched races in neuropharmacology. A small but intriguing Mt-Sinai sponsored study comparing ketamine with the anesthetic midazolam just reported its results: In the 72 pt trial, there was a response rate (on the MADRS) of 63.8% for the 47 patients who had received IV ketamine 24 hours previously, compared with 28% in the midazolam group. The value of the midazolam control was that there is an unmistakable, immediate psychotropic effect with IV ketamine that is not emulated by placebo, but is mimicked by midazolam. However, the glutamatergic premise behind ketamine’s postulated antidepressant effect would not be mirrored by midazolam, and indeed the much higher rate of response indicates that ketamine’s action is not a nonspecific psychotropic one. The degree of MADRS change was also much greater in the ketamine group, 16.5 points versus 8.8 points. Interestingly since BDNF upregulation is one of the hypothesized mechanisms of action for ketamine, BDNF plasma levels were monitored, and BDNF level changes were higher in treatment responders, but only in the ketamine group. Ketamine is not without its complications, and indeed, the investigators reported changes “in the level of dissociation” during the ketamine infusion, which abated within a few minutes for most, but took up to four hours to abate for others. Even though the investigator referred to this as “very little in the way of psychotic effects,” any psychotomimetic effect is going to alter the perceived risk-benefit calculus, and put more pressure on clinics administering the drug to provide prolonged monitoring. Since this was a single-infusion, single read-out study, no further information regarding the durability of the ketamine response was produced. This is another piece of evidence that supports the RAAD concept. With the consistent report of at least transient and mild dissociative symptoms for ketamine, there will be even more attention given to the Naurex GlyX-13 Phase IIb, now well underway: Thus far, no dissociative/psychotomimetic reactions have been reported with GlyX-13.

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