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

This retrospective analysis (n=164) assessed the rates of symptomatic worsening in patients with unipolar and bipolar treatment-resistant depression (TRD) following a two-week course of IV ketamine. Using the QIDS-SR16 to assess symptoms, it was found that clinically significant worsening for those with unipolar TRD fluctuated between 1.83% to 5.49%, while no participants with bipolar TRD reported symptomatic worsening. Rates of symptomatic worsening were similar to conventional antidepressants.


“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.”

Authors: Joshua 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


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