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

Objective: The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known. Methods: Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning. Results: A significant improvement was found only in scores of speed of processing (F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline (r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04). Conclusion: This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD.