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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

Psychiatry Research 2022 DOI: 10.1016/j.psychres.2021.114321 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Retrospective analysis Peer reviewed
Sample size 164
Population Adults with treatment-resistant depression (unipolar and bipolar)
Dose 0.5-0.75 mg/kg over 40 min
Duration Four infusions over two weeks
Measures Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16)
Topics Depression Ketamine Esketamine
Keywords Bipolar Crtce Worsening
Citations 11
Key points Clinically significant worsening of depressive symptoms occurred in 1.83% to 5.49% of patients across infusion time points, with no worsening observed in the bipolar subgroup.

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.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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