Distinct trajectories of antidepressant response to intravenous ketamine

This open-label study (n=328) found that people who were depressed, for those with childhood physical abuse responded best to ketamine (48mg/70kg) treatment. This analysis was done retrospectively and the analysis consisted of breaking the group in three parts (responders, non-responders, responders with lower initial depression scores).


Background: The N-methyl-D-aspartate receptor antagonist ketamine is potentially effective in treatment resistant depression. However, its antidepressant efficacy is highly variable, and there is little information about predictors of response.

Methods: We employed growth mixture modeling (GMM) analysis to examine specific response trajectories to intravenous (IV) ketamine (three infusions; mean dose 0.63 mg/kg, SD 0.28, range 0.30 – 2.98 mg/kg over 40 min) in 328 depressed adult outpatients referred to a community clinic. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) assessed depression severity at baseline and before each infusion, up to three infusions for four total observations.

Results: GMM revealed three QIDS-SR response trajectories. There were two groups of severely depressed patients, with contrasting responses to ketamine. One group (n=135, baseline QIDS-SR=18.8) had a robust antidepressant response (final QIDS-SR=7.3); the other group (n=97, QIDS-SR=19.8) was less responsive (final QIDS-SR=15.6). A third group (n=96) was less severely depressed at baseline (QIDS-SR=11.7), with intermediate antidepressant response (final QIDS-SR=6.6). Comparisons of demographic and clinical characteristics between groups with severe baseline depression revealed higher childhood physical abuse in the group with robust ketamine response (p=0.01).

Limitations: This was a retrospective analysis on a naturalistic sample. Patients were unblinded and more heterogenous than those included in most controlled clinical trial samples. Information pertaining to traumatic events occurring after childhood and pre-existing or concurrent medical conditions that may have affected outcomes was not available.

Conclusions: Overall, ketamine’s effect in patients with severe baseline depression and history of childhood maltreatment may be consistent with ketamine-induced blockade of behavioral sensitization.

Authors: Brittany O’Brien, Marijn Lijffijt, Jaehoon Lee, Ye Sil Kim, Allison Wells, Nicholas Murphy, Nithya Ramakrishnan, Alan C. Swann & Sanjay J. Mathew

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Distinct trajectories of antidepressant response to intravenous ketamine


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Published in
Journal of Affective Disorders
May 1, 2021
1 citations

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