Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression
Paulo R. Shiroma, C. Sophia Albott, Brian Johns, Paul Thuras, Joseph Wels and
Kelvin O. Lim
The International Journal of Neuropsychopharmacology, 2014, Volume 17, Issue 11, 1805–1813,
Doi : 10.1017/S1461145714001011
Ketamine, a non-competitive, high-affinity antagonist of the N-methyl-D-aspartate (NMDA) type glutamate receptor used for induction and maintenance of anesthesia (Green and Li, 2000), has been recently investigated for its high efficacy and rapid antidepressant effect. However, side effects of ketamine have raised some concerns. In 2013, the United Kingdom government upgraded ketamine from a Class C drug to a Class B drug based on recommendations from the Advisory Council on the Misuse of Drugs concerning bladder damage on ketamine drug users with ‘more research needed on the long-term neurocognitive effects’.
Studies in healthy subjects suggested that subanesthetic doses of ketamine as a psychopharmacologic probe disrupt information encoding that occurs during drug administration but does not impair recall for previously learned information (Morgan et al., 2004; Krystal et al., 2005). Other studies have found evidence for selective impairments in aspects of executive functioning (Krystal et al., 1994b; Morgan et al., 2009), while no impairments have been reported (Morgan et al., 2004; Parwani et al., 2005). Ketamine administration at subanesthetic doses appears to carry a very low risk of adverse events in experimental psychopharmacology studies (Perry et al., 2007). These findings are consistent with the lack of long-term effects reported with anesthetic doses of ketamine (Corssen et al., 1971; Moretti et al., 1984).
Given recent interest of ketamine use in treatment-resistant depression (TRD), the neurocognitive effects has just started to be explored. Murrough and colleagues (Murrough et al., 2013b) reported impairments in memory recall immediately after a single ketamine infusion was completed. The strategy of repeated ketamine infusions suggest that more than a single infusion achieve better antidepressant outcomes (Murrough et al., 2013a; Rasmussen et al., 2013; Shiroma et al., 2014); however, the short-term neurocognitive effects after completion of treatment are not known.
This study aims to (1) examine the association of baseline neurocognitive performance and the change in severity of depressive symptoms through six consecutive infusions among TRD subjects, (2) examine the neurocognitive effects of serial ketamine infusions during follow-up and whether changes in neurocognition were associated to relapse from antidepressant response.