Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression : A systematic review and meta-analysis
Copyright © 2024 Elsevier B.V. All rights reserved..
OBJECTIVE: Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression.
METHODS: We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects.
RESULTS: A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18-0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose.
LIMITATIONS: Overall quality of evidence was low and limited by small number of studies. Publication bias was high.
CONCLUSIONS: This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:356 |
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| Enthalten in: |
Journal of affective disorders - 356(2024) vom: 01. Mai, Seite 379-384 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Seshadri, Ashok [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.05.2024 Date Revised 06.05.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jad.2024.03.137 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370273052 |
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| 100 | 1 | |a Seshadri, Ashok |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression |b A systematic review and meta-analysis |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a OBJECTIVE: Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression | ||
| 520 | |a METHODS: We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects | ||
| 520 | |a RESULTS: A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p < 0.001) and IN esketamine (Hedges' g = 0.31 [0.18-0.44], Z = 4.53, P < 0.001) compared to control/placebo. Treatment response was observed at IV ketamine doses ≤0.2 mg/kg, >0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose | ||
| 520 | |a LIMITATIONS: Overall quality of evidence was low and limited by small number of studies. Publication bias was high | ||
| 520 | |a CONCLUSIONS: This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Systematic Review | |
| 650 | 4 | |a Meta-Analysis | |
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| 650 | 4 | |a Intravenous ketamine | |
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| 700 | 1 | |a Prokop, Larry J |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Balwinder |e verfasserin |4 aut | |
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