Evidence map›Paper›PMID 33929660›Full record

SynthesisAdvances in therapy2021

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, Roger Ho, Nelson B Rodrigues, Joshua D Rosenblat, Bing Cao, Hartej Gill and 3 more

Registry-linked trialAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Advances in therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06620276 (Acceptance and Commitment Therapy in Patients With Alcohol Use Disorder and Comorbid Treatment-Resistant Depression Who Are Undergoing Ketamine Intervention), which is not on this map. Cited by 23 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06620276 narecruitingnot on this mapstarted 2025, after this paper: background citation

Acceptance and Commitment Therapy in Patients With Alcohol Use Disorder and Comorbid Treatment-Resistant Depression Who Are Undergoing Ketamine Intervention: A Feasibility Study

TypeinterventionalSponsorCentre hospitalier de l'Université de Montréal (CHUM)Ran2025 to 2028Enrolled30ConditionsDepression - Major Depressive Disorder, Alcohol Use DisorderArmsAcceptance and Commitment Therapy, Ketamine
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Review
  6. Article
  7. Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025
    Review
  8. Article
  9. Chronic, combinatorial targeting of NMDARs and 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  10. Article
  11. The why, when, where, how, and so what of so-called rapidly acting antidepressants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Eric P McMullenMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Yena LeeMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Orly LipsitzMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Leanna M W LuiMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Maj VinbergFaculty of Health and Medical Sciences, Department of Clinical Medicine, Psychiatric Research Unit, University of Copenhagen, Psychiatric Centre North Zealand, Hilleroed, Denmark.
Roger HoInstitute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore.
Nelson B RodriguesMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Joshua D RosenblatMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Bing CaoKey Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, 400715, People's Republic of China.
Hartej GillMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Kayla M TeopizMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Danielle S ChaMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada.
Roger S McIntyreMood Disorder Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, MP 9-325, Toronto, ON, M5T 2S8, Canada. roger.mcintyre@uhn.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionKetamine 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.

methodsPubMed/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.

resultsA 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.

conclusionHitherto, 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.

Indexed as

Depressive Disorder, Treatment-ResistantKetamineAdultAntidepressive AgentsDepressionHumansPsychotherapyAntidepressive AgentsKetamineAnxietyBipolar disorderDepressionEsketamineKetamineMajor depressive disorderSuicidalityTreatment-resistant depression

Identifiers

PMID33929660
PMCPMC8189962

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.