Frequency analysis of symptomatic worsening following ketamine infusions for treatment resistant depression in a real-world sample: Results from the canadian rapid treatment center of excellence

Joshua D Di Vincenzo; Orly Lipsitz; Nelson B Rodrigues; Brett D M Jones; Hartej Gill; Yena Lee; Leanna M W Lui; Kayla M Teopiz; Roger Ho; Kangguang Lin; Flora Nasri; Roger S McIntyre; Joshua D Rosenblat

doi:10.1016/j.psychres.2021.114321

Frequency analysis of symptomatic worsening following ketamine infusions for treatment resistant depression in a real-world sample: Results from the canadian rapid treatment center of excellence

Psychiatry Res. 2022 Jan:307:114321. doi: 10.1016/j.psychres.2021.114321. Epub 2021 Dec 2.

Authors

Affiliations

¹ Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King's College Cir Room 4207, M5S 1A8, Toronto, ON, Canada.
² Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada.
³ Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, M5T 1R8, Toronto, ON, Canada.
⁴ Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada.
⁵ Department of Psychological Medicine, National University Health System, Singapore, Singapore; Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
⁶ Department of Affective Disorders, The Affiliated Brain Hospital of Guangzhou Medical University.
⁷ Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, M5T 1R8, Toronto, ON, Canada. Electronic address: roger.mcintyre@uhn.ca.
⁸ Mood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada; Canadian Rapid Treatment Center of Excellence, Mississauga, ON, Canada; Department of Psychiatry, University of Toronto, 250 College Street, 8th floor, M5T 1R8, Toronto, ON, Canada.

PMID: 34890909
DOI: 10.1016/j.psychres.2021.114321

Abstract

Antidepressants are associated with symptomatic worsening in a subgroup of patients. Replicated evidence has demonstrated rapid and robust antidepressant effects with intravenous (IV) ketamine in treatment resistant depression (TRD); however, the risk of ketamine worsening depressive symptoms in a subgroup of patients remains unknown. Herein we report a retrospective analysis on the rates of symptomatic worsening during an acute course of IV ketamine in individuals with unipolar (n = 142) and bipolar (n = 22) TRD. Adults (N = 164; mean age = 45.97) with TRD underwent four sub-anesthetic infusions (0.5-0.75 mg/kg over 40 min) of IV ketamine over two weeks, and were assessed with the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR₁₆) at baseline and after each infusion. The primary outcome was the proportion of patients experiencing clinically significant worsening of depressive symptoms (≥20% increase on the QIDS-SR₁₆) at each time point relative to baseline. Secondary analyses explored trends in the results. The frequency of clinically significant worsening fluctuated between 1.83% to 5.49%, with no identifiable trend across time. Zero individuals with bipolar TRD reported symptomatic worsening. Limitations include the single-centered, uncontrolled, retrospective nature of this study. Rates of symptomatic worsening associated with IV ketamine therapy for TRD appear to be very low and similar to conventional antidepressants.

Keywords: Bipolar; CRTCE; Depression; Ketamine; Worsening.

Publication types

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

MeSH terms

Adult
Canada / epidemiology
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Treatment-Resistant* / drug therapy
Humans
Infusions, Intravenous
Ketamine* / adverse effects
Middle Aged
Retrospective Studies

Substances

Ketamine

Grants and funding

CIHR/Canada