Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions

Jennifer L Phillips; Amanda Van Geel; Patricia Burhunduli; Dominique Vasudev; Lisa A Batten; Sandhaya Norris; Jeanne Talbot; Abigail Ortiz; Olabisi Owoeye; Pierre Blier

doi:10.1093/ijnp/pyac045

Assessment of Objective and Subjective Cognitive Function in Patients With Treatment-Resistant Depression Undergoing Repeated Ketamine Infusions

Int J Neuropsychopharmacol. 2022 Dec 12;25(12):992-1002. doi: 10.1093/ijnp/pyac045.

Authors

Jennifer L Phillips^{1

2

3

4}, Amanda Van Geel^{1

3}, Patricia Burhunduli^{1

5}, Dominique Vasudev^{1

3}, Lisa A Batten¹, Sandhaya Norris^{1

2

3}, Jeanne Talbot^{1

2

3}, Abigail Ortiz^{1

2

3

6

7}, Olabisi Owoeye^{1

2

3}, Pierre Blier^{1

2

3

5}

Affiliations

¹ University of Ottawa Institute of Mental Health Research at The Royal, Ottawa, Ontario, Canada.
² Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada.
³ Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
⁴ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada.
⁵ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁶ Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Abstract

Background: Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment.

Methods: Thirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report.

Results: Twenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37-0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η p2 = 0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P < .001, d = 2.00; Quick Inventory of Depressive Symptoms Self-Report item 10, P < .001, d = 1.36).

Conclusion: A short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier NCT01945047.

Keywords: Treatment-resistant depression; intravenous ketamine; major depressive disorder; neurocognitive function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cognition
Depression / drug therapy
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Treatment-Resistant* / drug therapy
Humans
Infusions, Intravenous
Ketamine* / adverse effects
Memory, Short-Term
Treatment Outcome

Substances

Ketamine

Associated data

ClinicalTrials.gov/NCT01945047

Grants and funding

274324/CIHR/Canada