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Non-improvement predicts subsequent non-response to repeated-dose intravenous ketamine for depression: a re-analysis of a 2-week open-label study in patients with unipolar and bipolar depression.

Chengyu Wang, Xiaofeng Lan, Weijian Liu, Yanni Zhan, Wei Zheng, Xiaoyu Chen, Guanxi Liu, Siming Mai, Hanna Lu, Roger S McIntyre, Yanling Zhou, Yuping Ning

Translational Psychiatry August 6, 2024 DOI: 10.1038/s41398-024-03027-2 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Open-label Peer reviewed
Sample size 135
Population Individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode
Intervention Intravenous ketamine
Dose six repeated doses
Duration Six infusions, with assessments at baseline, 4 hours after first infusion, and 24 hours after each infusion
Topics Depression Esketamine Ketamine
Keywords Depression treatment Ketamine therapy Mental health research Treatment response prediction
Citations 6
Key findings Non-improvement after four infusions, or three consecutive non-improvements after three infusions, predicts overall non-response to repeated-dose intravenous ketamine for depression with sensitivities exceeding 90%.

Abstract

There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

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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