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Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

Eric P. Mcmullen, Yena Lee, Orly Lipsitz, Leanna M.W. Lui, Maj Vinberg, R. Ho, Nelson B Rodrigues, Joshua D. Rosenblat, Bing Cao, Hartej Gill, Kayla M Teopiz, Danielle S. Cha, Roger S McIntyre

Advances in Therapy April 30, 2021 DOI: 10.1007/s12325-021-01732-8 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Open-label Peer reviewed
Population Adults with treatment-resistant depression
Topics Depression Esketamine Ketamine
Key findings No treatment modality other than repeat-dose intravenous ketamine has demonstrated the ability to significantly prolong the acute antidepressant effects of ketamine in adults with treatment-resistant depression.

Abstract

Ketamine treatment is capable of significant and rapid symptom improvement in adults with treatment-resistant depression (TRD). A limitation of ketamine treatment in TRD is the relatively short duration of time to relapse (e.g., median 2–4 weeks). The objective of the systematic review herein is to identify strategies capable of prolonging the acute efficacy of ketamine in adults with TRD. PubMed/MEDLINE databases were searched from inception to December 2020 for clinical studies written in English using the following key terms: ketamine, prolong, and depression. A total of 454 articles were identified from the literature search which included all clinical studies regarding prolonging the antidepressant effects of ketamine. Twenty-two articles were included: ten randomized controlled trials (RCTs), eight prospective open-label trials, one retrospective chart review, and three case reports. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data extraction. The primary outcome was prolonged effect, defined as statistically significant antidepressant effects following acute ketamine treatment. A total of 454 articles were identified, and 22 articles were included. Different treatment modalites including pharmacological interventions, manualized-based psychotherapies, electroconvulsive therapy, transcranial magnetic stimulation, and intravenous monotherapy were examined to determine their impact on the prolongation of antidepressant effects following acute ketamine treatment. No treatment modality, other than repeat-dose IV ketamine, has demonstrated ability to significantly prolong the acute efficacy of IV ketamine in TRD. Hitherto, available open-label data and controlled trial data support repeat administration of IV ketamine as an effective strategy to prolong the efficacy of ketamine’s antidepressant effects (although not the focus of the study herein, maintenance repeat-dose esketamine treatment is proven effective in esketamine responders). There is a need to identify multimodality strategies that are safe and capable of prolonging the efficacy of ketamine in adults with TRD.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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