Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis

Bahji, Anees; Vázquez, Gustavo; Zarate, Carlos A.

doi:10.1016/j.jad.2020.09.071

Cited by 210 publications

(165 citation statements)

References 98 publications

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“…IN esketamine appeared to solve some of these problems with practical dispositive and feasibility, leading to its approval by several regulatory agencies throughout the world. However, there is a possible impact on efficacy when using IN esketamine (42). The IM and SC routes appear to be somewhat practical, but as we found in this review regarding SC, the studies in the literature are still few.…”

Section: Future Perspectivesmentioning

confidence: 84%

Subcutaneous Ketamine in Depression: A Systematic Review

et al. 2021

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Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability.Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool.Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5–1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects.Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted.Systematic Review Registration: CRD42019137434

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Section: Future Perspectivesmentioning

confidence: 84%

Subcutaneous Ketamine in Depression: A Systematic Review

et al. 2021

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“…In order to understand the state of the literature regarding the measurement of expectancy, de-masking and alliance in psychedelic trials, we conducted several systematic reviews. Firstly, we examined placebo controlled RCTs of ketamine for the treatment of major depressive disorder since a relatively large number of trials exist in this area and there are recent systematic reviews of this topic [78,79]. Secondly, we searched for trials of classical serotonergic psychedelics.…”

Section: Reporting Of Masking and Expectancy In Psychedelic Rctsmentioning

confidence: 99%

Blinding and expectancy confounds in psychedelic randomized controlled trials

Muthukumaraswamy

Forsyth

Lumley

2021

Expert Review of Clinical Pharmacology

147

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There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat a number of mental health disorders. To gain evidence for the therapeutic effectiveness of psychedelics, a number of randomised controlled trials (RCTs) have been conducted using the traditional RCT framework and these trials have generally shown promising results, with large effect sizes reported. However, in this paper we argue that estimation of treatment effect sizes in psychedelic clinical trials are likely over-estimated due to de-blinding of participants and high levels of response expectancy generated by RCT trial contingencies. The degree of over-estimation is at present difficult to estimate. We conduct systematic reviews of psychedelic RCTs and show that currently reported RCTs have failed to measure and report expectancy and malicious de-blinding. In order to overcome these confounds we argue that RCTs should routinely measure de-blinding and expectancy and that careful attention should be paid to the clinical trial design used and the instructions given to participants to allow these confounds to be estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.

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“…A few trials have indicated a role for electroconvulsive therapy and repetitive transcranial magnetic stimulation ( Schoeyen et al, 2015 ; Tavares et al, 2017 ). While recent network meta-analyses have shown consistent evidence for use of multiple pharmacotherapies in non-TRBD ( Bahji et al, 2020a , 2020b , 2021a , 2021c ), there is more limited evidence for use of medication-based treatments in TRBD.…”

Section: Introductionmentioning

confidence: 99%

“…Fortunately, there appears to be an emerging role for ketamine in managing unipolar depression ( McIntyre et al, 2020 ; Bahji et al, 2021b , 2021c ). Early ketamine studies demonstrated rapid, potent reductions in depressive symptoms following administration of a single sub-anesthetic dose of intravenous racemic ketamine ( Berman et al, 2000 ; Zarate et al, 2006 ; Ionescu et al, 2015 ; Hu et al, 2016 ; Wilkinson et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Ketamine for Bipolar Depression: A Systematic Review

Bahji

Zarate

Vázquez

2021

International Journal of Neuropsychopharmacology

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Background Ketamine appears to have a therapeutic role in certain mental disorders, most notably unipolar major depressive disorder. However, its efficacy in bipolar depression is less clear. This study aimed to assess the efficacy and tolerability of ketamine for bipolar depression. Methods We conducted a systematic review of experimental studies using ketamine for the treatment of bipolar depression. We searched PubMed, MEDLINE, Embase, PsycINFO, and the Cochrane Central Register for relevant studies published since each database’s inception. We synthesized evidence regarding efficacy (improvement in depression rating scores) and tolerability (adverse events, dissociation, dropouts) across studies. Results We identified 6 studies, with 135 participants (53% female; 44.7 years; standard deviation, 11.7 years). All studies used 0.5 mg/kg of add-on intravenous racemic ketamine, with the number of doses ranging from 1 to 6; all participants continued a mood-stabilizing agent. The overall proportion achieving a response (defined as those having a reduction in their baseline depression severity of at least 50%) was 61% for those receiving ketamine and 5% for those receiving a placebo. The overall response rates varied from 52% to 80% across studies. Ketamine was reasonably well tolerated; however, 2 participants (1 receiving ketamine and 1 receiving placebo) developed manic symptoms. Some participants developed significant dissociative symptoms at the 40-minute mark following ketamine infusion in 2 trials. Conclusions There is some preliminary evidence supporting use of intravenous racemic ketamine to treat adults with bipolar depression. There is a need for additional studies exploring longer-term outcomes and alterative formulations of ketamine.

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Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis

Cited by 210 publications

References 98 publications

Subcutaneous Ketamine in Depression: A Systematic Review

Subcutaneous Ketamine in Depression: A Systematic Review

Blinding and expectancy confounds in psychedelic randomized controlled trials

Ketamine for Bipolar Depression: A Systematic Review

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