Dataset Information

Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.

ABSTRACT:

Background

Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression.

Research design and methods

We conducted a PRISMA-guided review for relevant randomized controlled trials of racemic or esketamine for unipolar or bipolar major depression from database inception through 2021. We conducted random-effects meta-analyses using pooled rate ratios (RRs) and Cohen's standardized mean differences (d) with their 95% confidence intervals (CI).

Results

We found 36 studies (2903 participants, 57% female, 45.1 +/- 7.0 years). Nine trials used esketamine, while the rest used racemic ketamine. The overall study quality was high. Treatment with any form of ketamine was associated with improved response (RR=2.14; 95% CI, 1.72-2.66; I2=65%), remission (RR=1.64; 95% CI, 1.33-2.02; I2=39%), and depression severity (d=-0.63; 95% CI, -0.80 to -0.45; I2=78%) against placebo. Overall, there was no association between treatment with any form of ketamine and retention in treatment (RR=1.00; 95% CI, 0.99-1.01; I2<1%), dropouts due to adverse events (RR=1.56; 95% CI, 1.00-2.45; I2<1%), or the overall number of adverse events reported per participant (OR=2.14; 95% CI, 0.82-5.60; I2=62%) against placebo.

Conclusions

Ketamine and esketamine are effective, safe, and acceptable treatments for individuals living with depression.

SUBMITTER: Bahji A

PROVIDER: S-EPMC9949988 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.

Bahji Anees A Zarate Carlos A CA Vazquez Gustavo H GH

Expert opinion on drug safety 20220309 6

<h4>Background</h4>Racemic ketamine and esketamine have demonstrated rapid antidepressant effects. We aimed to review the efficacy and safety of racemic and esketamine for depression.<h4>Research design and methods</h4>We conducted a PRISMA-guided review for relevant randomized controlled trials of racemic or esketamine for unipolar or bipolar major depression from database inception through 2021. We conducted random-effects meta-analyses using pooled rate ratios (RRs) and Cohen's standardized m ...[more]

PMID: 35231204

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Project description:BackgroundUnipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile.MethodsFollowing PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted.ResultsOur analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence.LimitationsThis study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression.ConclusionWhile ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression.Systematic review registration[https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).

Project description:INTRODUCTION:The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression. METHODS/DESIGN:This study protocol is for a randomized, controlled, double-blind noninferiority clinical trial. Subjects will be 18 years or older, with major depression characterized as treatment-resistant. Participants will receive a single infusion of either esketamine (0.25?mg/kg) or ketamine (0.5?mg/kg) over 40 minutes. The primary outcome will be the difference in remission rates between the 2 treatment arms at 24 and 72?hours after drug infusion. Secondary outcomes will include other timepoints, measurements of cognition, dissociation, and blood biomarkers. DISCUSSION:A head-to-head study is the best way to evaluate whether the esketamine is in fact comparable to the racemic ketamine in terms of both efficacy and safety, and, if positive, it would be an initial step to increase the access to that type of treatment worldwide. ETHICS AND DISSEMINATION:The study was approved by the local Institutional Review Board (University Hospital Professor Edgard Santos-Federal University of Bahia-Number: 46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing and signing the Informed Consent Form. The study findings will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION:This trial has been registered in the Japan Primary Registries Network (JPRN): UMIN000032355, which is affiliated with the World Health Organization.

Project description:BackgroundPatients who undergo gastrointestinal endoscopy often require propofol-based sedation combined with analgesics. At present, the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients remains controversial. Moreover, there is no universal agreement regarding the appropriate dose of esketamine supplementation. This study aimed to assess the efficacy and safety of esketamine as an adjunct to propofol for sedation during endoscopic procedures in patients.MethodsSeven electronic databases and three clinical trial registry platforms were searched and the deadline was February 2023. Randomized controlled trials (RCTs) evaluating the efficacy of esketamine for sedation were included by two reviewers. Data from the eligible studies were combined to calculate the pooled risk ratio or standardized mean difference.ResultsEighteen studies with 1962 esketamine participants were included in the analysis. As an adjunct to propofol, the administration of esketamine reduced the recovery time compared to normal saline (NS). However, there was no significant difference between the opioids group and ketamine group. For propofol dosage, the administration of esketamine required a lower propofol dosage compared to the NS group and opioids group].For complications, the esketamine group had fewer complications compared to the NS group and opioid group in patients, but there were no significant differences between the esketamine group and ketamine group. Notably, the coadministration of esketamine was associated with a higher risk of visual disturbance compared to the NS group. In addition, we used subgroup analysis to investigate whether 0.2-0.5 mg/kg esketamine was effective and tolerable for patients.ConclusionEsketamine as an adjunct to propofol, is an appropriate effective alternative for sedation in participants undergoing gastrointestinal endoscopy. However, considering the possibility of its psychotomimetic effects, esketamine should be used with caution.

Dataset Information

Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.

Background

Research design and methods

Results

Conclusions

Publications

Efficacy and safety of racemic ketamine and esketamine for depression: a systematic review and meta-analysis.

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