Psychiatry researchDec 10, 2021

How often symptoms get worse after ketamine infusions in hard-to-treat depression: Data from a Canadian treatment center

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

The frequency of clinically significant worsening of depressive symptoms during IV ketamine treatment for treatment-resistant depression ranges from 1.83% to 5.49%.

A total of 164 adults with treatment-resistant depression were analyzed.
Symptomatic worsening was defined as a ≥20% increase in scores on the Quick Inventory for Depression Symptomatology-Self Report-16.
No patients with bipolar treatment-resistant depression reported symptomatic worsening.
The rates of worsening observed are comparable to those associated with conventional antidepressants.
The results are based on a retrospective analysis and have limitations due to the study's single-centered and uncontrolled design.

Simplified

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-SR) 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-SR) 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. 16 16

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How often symptoms get worse after ketamine infusions in hard-to-treat depression: Data from a Canadian treatment center

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