Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder

Objective: Ketamine has demonstrated a rapid antidepressant and antisuicidal effect in patients with major depressive disorder (MDD), but the neurocognitive effects of ketamine are relatively unknown. This study aims to examine the neurocognitive effects of six ketamine infusions and the association of baseline neurocognitive function and the change in severity of depressive symptoms after the last infusions. Methods: Sixty-four patients with MDD completed six intravenous infusions of ketamine (0.5 mg/kg over 40 min) administered over a 12-day period (Monday-Wednesday-Friday), and were followed by a 2-week observational period. Four domains of neurocognitive function (including speed of processing, working memory, visual learning and verbal learning) were assessed using the MATRICS Consensus Cognitive Battery (MCCB) at 0, 13 and 26 days. Results: In linear mixed model, significant improvements were found in terms of speed of processing (F = 20.7, p < 0.001) and verbal learning (F = 11.1, p < 0.001). The Sobel test showed the improvement of speed of processing (Sobel test = 2.8, p < 0.001) and verbal learning (Sobel test = 3.6, p < 0.001) were significantly mediated by change in depressive symptoms. Other two neurocognitive domains showed no significant changes over time. Correlation analysis showed no significant association of change in depressive symptoms with neurocognitive function at baseline. Conclusion: Our findings suggest that six ketamine infusions were associated with the improvement of speed of processing and verbal learning, which were partly accounted for by improvement in the severity of depression symptoms over time.