The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis

McIntyre, Roger S.; Carvalho, Isabelle P.; Lui, Leanna M.W.; Majeed, Amna; Masand, Prakash S.; Gill, Hartej; Rodrigues, Nelson B.; Lipsitz, Orly; Coles, Alexandria C.; Lee, Ye-Na; Tamura, Jocelyn K.; Iacobucci, Michelle; Phan, Lee; Nasri, Flora; Singhal, Nikhita; Wong, Elizabeth; Subramaniapillai, Mehala; Mansur, Rodrigo B.; Ho, Roger; Lam, Raymond W.; Rosenblat, Joshua D.

doi:10.1016/j.jad.2020.06.050

Cited by 130 publications

(107 citation statements)

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“…During the past two decades, the rapid antidepressant effects of ketamine have been reported in adults with treatment-resistant depression (TRD) [7]. Racemic ketamine, as well as esketamine, have demonstrated significant and rapid symptom improvement as well as anti-suicidality effects in adults with TRD [8][9][10]. Notwithstanding the efficacy of ketamine in adults with TRD, a major limitation is the relatively short duration to relapse (e.g., median 2-4 weeks) [11].…”

Section: Introductionmentioning

confidence: 99%

“…Multiple clinical studies have reported the maintenance antidepressant effects of repeat sub-anesthetic dose intravenous (IV) ketamine for up to 6 weeks, with replicated large effect sizes [9,[12][13][14]. Compared to conventional antidepressants, IV ketamine is differentiated by (1) efficacy in patients with TRD, (2) a relatively rapid onset of therapeutic effect, and (3) preliminary evidence for reducing suicidality [10,15].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Introduction 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. Methods 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. Results 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. Conclusion 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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…They revealed a rapid reduction of depressive symptoms 4 hours after the first dosing; however, this reduction did not reach statistical significance against the placebo’s results on day 25 (Canuso et al, 2018). In a recent meta-analysis (McIntyre et al, 2020), the short-term efficacy of IV and IN ketamine/esketamine for adults with TRD was established.…”

Section: Discussionmentioning

confidence: 99%

Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

et al. 2021

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Background: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. Results: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.

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“…For example, 8 RCTs all found intranasal esketamine to be superior to control treatment in patients with depression, and the meta-analysis provided a pooled estimate of the magnitude of the treatment effect. 10…”

Section: E2mentioning

confidence: 99%

Understanding the Basics of Meta-Analysis and How to Read a Forest Plot

Andrade¹

2020

J. Clin. Psychiatry

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The results of research on a specific question differ across studies, some to a small extent and some to a large extent. Meta-analysis is a way to statistically combine and summarize the results of different studies so as to obtain a pooled or summary estimate that may better represent what is true in the population. Meta-analysis can be conducted for a variety of statistics, including means, mean differences, standardized mean differences, proportions, differences in proportions, relative risks, odds ratios, and others. The results of metaanalysis are presented in forest plots. This article explains why meta-analysis may be necessary, how a systematic review is conducted to identify studies for meta-analysis, and how to interpret the various elements in a forest plot. Brief discussions are provided about important concepts relevant to meta-analysis, including heterogeneity, subgroup analyses, sensitivity analyses, fixed effect and random effects meta-analyses, and the detection of publication bias. Other procedures briefly explained include meta-regression analysis, pooled analysis, individual participant data meta-analysis, and network meta-analysis. The limitations of meta-analysis are also discussed.

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The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis

Cited by 130 publications

References 42 publications

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

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

Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

Understanding the Basics of Meta-Analysis and How to Read a Forest Plot

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