Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression

Abstract

Background: Ketamine has proven to have rapid, robust antidepressant effects on treatment-resistant depression. However, whether repeated ketamine infusions would cause short-and long-term neurocognitive impairments was not clear. Our aims were to investigate the neurocognitive effects of six ketamine infusions and to examine the association between these infusions and the antidepressant response in patients with unipolar and bipolar depression. Methods: Six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period were administered to 84 patients with unipolar and bipolar depression. Severity of depressive symptoms and four domains of neurocognition, including speed of processing, working memory, visual learning and verbal learning, were assessed at baseline, one day following the last infusion and again two weeks post-infusion. Results: Significant improvements were found on speed of processing (F=9.344, p<0.001) and verbal learning (F=5.647, p=0.004) in a linear mixed model. The Sobel test showed significant indirect effects between time and improvement in speed of processing (Sobel test=3.573, p<0.001) as well as improvement in verbal learning (Sobel test=6.649, p<0.001), which were both significantly mediated by change in depressive symptoms. Logistic regression analysis showed ketamine responders had better visual learning at baseline than non-responders (B=0.118, p<0.001). Conclusions: Our findings suggest that neurocognitive function would not deteriorate after six ketamine infusions, while verbal learning and speed of processing improved over 13 days and 26 days of observation, respectively. However, this change was mainly accounted for by improvements in severity of depressive symptoms over time. Greater baseline visual learning predicted an antidepressant response over six ketamine infusions.

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

“…During the infusion period, patients continued taking the same stable dosages of therapeutic medications they had received before the study. Additional details regarding the study procedure are given in our previous report 36 . Whole-blood samples were obtained at baseline and 24 h and 14 days after the sixth infusion (days 0, 13, and 26).…”

Neurocognitive impairment and evidence-based treatment options in Bipolar disorder

“…A randomized, open-label, pilot study, on euthymic BD-I patients supported the use of adjunctive lurasidone adjunctive in improving cognition [ 125 ]. A more recent study reported that six intravenous infusions of ketamine (0.5 mg/kg) over a 12-day period improved the speed of processing and verbal learning but it seemed that the improvement in depression mediated these results, with better baseline neurocognitive function being predictive of a better outcome [ 126 ].…”

Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study

“…However, the short-term neurocognitive effects of repeated intravenous infusions of ketamine at subanaesthetic doses targeting on TRBD are not known. Importantly, Zhou et al (2018) found that greater baseline visual learning could predict the antidepressant effects of six ketamine infusions for patients with unipolar and bipolar depression.…”