The effect of intravenous ketamine on cognitive functions in adults with treatment-resistant major depressive or bipolar disorders: Results from the Canadian rapid treatment center of excellence (CRTCE)

Roger S McIntyre; Joshua D Rosenblat; Nelson B Rodrigues; Orly Lipsitz; David Chen-Li; Jung Goo Lee; Flora Nasri; Mehala Subramaniapillai; Kevin Kratiuk; Andrew Wang; Hartej Gill; Rodrigo B Mansur; Roger Ho; Kangguang Lin; Yena Lee

doi:10.1016/j.psychres.2021.113993

The effect of intravenous ketamine on cognitive functions in adults with treatment-resistant major depressive or bipolar disorders: Results from the Canadian rapid treatment center of excellence (CRTCE)

Psychiatry Res. 2021 Aug;302:113993. doi: 10.1016/j.psychres.2021.113993. Epub 2021 May 13.

Authors

Affiliations

¹ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada. Electronic address: Roger.McIntyre@uhn.c.
² Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada.
⁴ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada.
⁵ Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan 48108, Republic of Korea; Paik Institute for Clinical Research, Inje University, Busan 47392, Republic of Korea; Department of Health Science and Technology, Graduate School, Inje University, Busan 47392, Republic of Korea.
⁶ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada.
⁷ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁸ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁹ Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore 119077, Singapore.
¹¹ Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Mood Disorders Psychopharmacology Unit, Poul Hansen Depression Centre, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan 48108, Republic of Korea; Paik Institute for Clinical Research, Inje University, Busan 47392, Republic of Korea; Department of Health Science and Technology, Graduate School, Inje University, Busan 47392, Republic of Korea; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore 119077, Singapore.

PMID: 34034067
DOI: 10.1016/j.psychres.2021.113993

Abstract

Ketamine may exert pro-cognitive effects on select measures of cognition in adults with mood disorders. We evaluated the effectiveness of intravenous (IV) ketamine on cognition in 68 adult outpatients with treatment-resistant depression (TRD) at the Canadian Rapid Treatment Center of Excellence between July 3, 2018 and April 16, 2020 (NCT04209296). Eligibility criteria for the present retrospective study included: primary diagnosis of major depressive or bipolar disorder; currently depressed; and insufficient response to two or more prior treatments. Participants received four infusions of ketamine hydrochloride (0.5-0.75 mg/kg) over 1-2 weeks. We assessed objective and subjective measures of cognition before and after two infusions, i.e., Digit Symbol Substitution Test (DSST), Trail Making Test-B (TMT-B), Patient Deficits Questionnaire, 5-item (PDQ-5-D). Ketamine significantly improved DSST (effect size [ES]=0.60), TMT-B (ES=0.84), as well as PDQ-5-D scores (ES=0.63), indicative of a moderate-to-large effect size. Improvements in DSST and PDQ-5-D with ketamine were mediated by reductions in depressive symptoms, whereas improvements in TMT-B were independent of changes in depressive symptoms. Our results support the independent, rapid-onset, pro-cognitive effects with IV ketamine in adults with TRD. Larger, randomized, controlled trials with ketamine wherein cognition is the primary outcome measure in mood and non-mood disorder samples are warranted.

Keywords: Bipolar disorder; Cognition; Depression; Disorders; Esketamine; Ketamine; Mood.

MeSH terms

Adult
Bipolar Disorder* / drug therapy
Canada
Cognition
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Treatment-Resistant* / drug therapy
Humans
Infusions, Intravenous
Ketamine* / therapeutic use
Retrospective Studies

Substances

Ketamine

Associated data

ClinicalTrials.gov/NCT04209296