Controversies of the Effect of Ketamine on Cognition

Over the last couple of years, there have been numerous studies investigating the efficacy of ketamine, a non-competitive N-methyl-d-aspartic acid (NMDA) receptor antagonist as a rapid antidepressant. Most of the existing published literature describes the purported effectiveness of ketamine as a rapid antidepressant. The clinical efficacy of intravenous ketamine in the reduction of suicidal ideations ranged between that of 29% to as much as 79%. Researchers have noted the transient nature of intravenous ketamine's rapid antidepressant efficacy and hence has recommended for long-term continued administration (1, 2). Clearly, with long-term utilization of ketamine, there are safety concerns and adverse effects that need to be considered. Prior systematic reviews have highlighted the acute adverse effects that could potential arise from the administration of intravenous ketamine (3). These adverse effects include that of dissociation, perceptual abnormalities, confusion, and transient instability in vital signs (3). Although studies have shown that serial infusions of ketamine in the short term (of 4 weeks) does not result in cognitive impairments (4), other studies have demonstrated that the administration of ketamine chronically would lead to memory impairments (5). More recently, Morgan et al. (5) in their recent article highlighted not only the increasing incidence of ketamine abuse globally but have also highlighted the mechanisms and implications of ketamine have on spatial memory. According to their study of 11 participants (of which 1 participants have had another mental health condition) who have been using ketamine recreationally, they discovered, through functional imaging studies that ketamine abusers experience spatial memory disturbances largely due to decreased activation in their right hippocampus and left parahippocampus gyrus (5). Morgan et al. (5) in their imaging studies also highlighted that chronic ketamine abusers do tend to experience dissociative symptoms, which are accounted for due to increased hippocampal activation. In addition, the functional studies also revealed that there are underlying disruption in the medial temporal lobe functioning. These resultant disruptions might also result in the psychotic symptoms that long-term ketamine abusers might experience. Clearly, the findings presented by Morgan et al. (5) are concerning if intravenous ketamine is being approved clinically and depressed individuals need to be receiving continuous administrations of intravenous ketamine. Although ketamine might seem like a promising antidepressant that could relieve treatment refractory depres-sive symptoms, the induction of memory impairments in the longer term is of concern. Memory impairments would result in further disabilities and consequential reduction in the overall quality of …