Repeated intravenous infusions of ketamine: Neurocognition in patients with anxious and nonanxious treatment-resistant depression

J Affect Disord. 2019 Dec 1:259:1-6. doi: 10.1016/j.jad.2019.08.012. Epub 2019 Aug 12.


Background: Recent studies have suggested that neurocognition is changed after repeated infusions of ketamine in patients with treatment-resistant depression (TRD). The objective of this study was to investigate whether differences existed in the neurocognitive effect of six ketamine infusions in patients with anxious and nonanxious TRD and to determine the association between baseline neurocognition and changes in symptoms after the infusions.

Method: Patients with anxious (n = 30) and nonanxious TRD (n = 20) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days. Speed of processing (SOP), working memory (WM), verbal learning and memory (VBM), visual learning and memory (VSM) and the severity of depressive and anxious symptoms were assessed at baseline, one day after the last infusion (day 13) and two weeks after the completion of the serial infusions (day 26). A linear mixed model was used to determine whether the neurocognitive changes differed between the two groups. Pearson correlation analysis was used to determine the relationship between baseline neurocognition and the changes in the symptomatic scores.

Results: Patients with anxious TRD had significant increases in SOP on day 13 and day 26 (both p < 0.001), and in VBM on day 13 (p = 0.028). However, no significant increase in any neurocognitive domain was found in patients with nonanxious TRD. Faster SOP at baseline was associated with greater improvement of anxious symptoms in patients with anxious TRD, and better VSM at baseline was associated with greater improvement of depressive symptoms in patients with nonanxious TRD.

Limitation: The major limitation of this study is the open-label design.

Conclusion: After six ketamine infusions, neurocognitive improvement was observed in patients with anxious TRD but not in patients with nonanxious TRD.

Keywords: Anxious treatment-resistant depression; Ketamine; Neurocognition; Repeated infusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Anxiety / complications
  • Anxiety / drug therapy*
  • Depressive Disorder, Treatment-Resistant / complications
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine / therapeutic use*
  • Male
  • Memory, Short-Term
  • Middle Aged
  • Treatment Outcome
  • Verbal Learning / drug effects


  • Antidepressive Agents
  • Ketamine