Dataset Information

The antidepressant effect and safety of non-intranasal esketamine: A systematic review.

ABSTRACT:

Background

The introduction of esketamine into the field of psychiatry comes on the heels of excitement from studies on racemic ketamine. While the intranasal route has been the most studied to date, other modes of administration of esketamine may also be of interest in the management of depression.

Aims

To systematically review the literature on non-intranasal esketamine for depression in terms of its antidepressant effect and safety.

Methods

We searched PubMed, Embase, the Cochrane Library, and Google Scholar from inception up to February 2021. Search terms included a combination of Medical Subject Headings and text words indicative of esketamine and depression. We selected both controlled and uncontrolled studies examining non-intranasal esketamine for the treatment of depression.

Results

We identified four randomized controlled trials (RCTs) on intravenous esketamine and 15 open-label studies on intravenous (n = 80), subcutaneous (n = 73), and oral (n = 5) esketamine. We found intravenous, subcutaneous, and possibly oral administration of esketamine to be effective in reducing depressive symptoms in most patients with major depressive disorder, bipolar depression, and (severe) treatment-resistant depression. Clinical response to repeated administration of esketamine persisted over the course of treatment. Esketamine was well tolerated by most patients, but open-label data indicate marked psychotomimetic symptoms in exceptional cases. The overall quality of the controlled studies was considered high, the overall quality of the uncontrolled studies low to moderate.

Conclusions

Intravenous, subcutaneous, and possibly oral esketamine may offer an effective and safe addition to the depression treatment armamentarium. However, as most included studies lacked a control group and had small sample sizes, the quality of our results is limited. Different types and formulations of ketamine remain to be compared directly.

SUBMITTER: Smith-Apeldoorn SY

PROVIDER: S-EPMC9112628 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

The antidepressant effect and safety of non-intranasal esketamine: A systematic review.

Smith-Apeldoorn Sanne Y SY Vischjager Maurice M Veraart Jolien Ke JK Kamphuis Jeanine J Aan Het Rot Marije M Schoevers Robert A RA

Journal of psychopharmacology (Oxford, England) 20220512 5

<h4>Background</h4>The introduction of esketamine into the field of psychiatry comes on the heels of excitement from studies on racemic ketamine. While the intranasal route has been the most studied to date, other modes of administration of esketamine may also be of interest in the management of depression.<h4>Aims</h4>To systematically review the literature on non-intranasal esketamine for depression in terms of its antidepressant effect and safety.<h4>Methods</h4>We searched PubMed, Embase, th ...[more]

PMID: 35546042

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Project description:ImportanceApproximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.ObjectiveTo assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD).Design, setting, and participantsThis phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015. The study consisted of 4 phases: (1) screening, (2) double-blind treatment (days 1-15), composed of two 1-week periods, (3) optional open-label treatment (days 15-74), and (4) posttreatment follow-up (8 weeks). One hundred twenty-six adults with a DSM-IV-TR diagnosis of MDD and history of inadequate response to 2 or more antidepressants (ie, TRD) were screened, 67 were randomized, and 60 completed both double-blind periods. Intent-to-treat analysis was used in evaluation of the findings.InterventionsIn period 1, participants were randomized (3:1:1:1) to placebo (n = 33), esketamine 28 mg (n = 11), 56 mg (n = 11), or 84 mg (n = 12) twice weekly. In period 2, 28 placebo-treated participants with moderate-to-severe symptoms were rerandomized (1:1:1:1) to 1 of the 4 treatment arms; those with mild symptoms continued receiving placebo. Participants continued their existing antidepressant treatment during the study. During the open-label phase, dosing frequency was reduced from twice weekly to weekly, and then to every 2 weeks.Main outcomes and measuresThe primary efficacy end point was change from baseline to day 8 (each period) in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.ResultsSixty-seven participants (38 women, mean [SD] age, 44.7 [10.0] years) were included in the efficacy and safety analyses. Change (least squares mean [SE] difference vs placebo) in MADRS total score (both periods combined) in all 3 esketamine groups was superior to placebo (esketamine 28 mg: -4.2 [2.09], P = .02; 56 mg: -6.3 [2.07], P = .001; 84 mg: -9.0 [2.13], P < .001), with a significant ascending dose-response relationship (P < .001). Improvement in depressive symptoms appeared to be sustained (-7.2 [1.84]) despite reduced dosing frequency in the open-label phase. Three of 56 (5%) esketamine-treated participants during the double-blind phase vs none receiving placebo and 1 of 57 participants (2%) during the open-label phase had adverse events that led to study discontinuation (1 event each of syncope, headache, dissociative syndrome, and ectopic pregnancy).Conclusions and relevanceIn this first clinical study to date of intranasal esketamine for TRD, antidepressant effect was rapid in onset and dose related. Response appeared to persist for more than 2 months with a lower dosing frequency. Results support further investigation in larger trials.Trial registrationclinicaltrials.gov identifier: NCT01998958.

Project description:BackgroundProcedural sedation and analgesia are commonly used in the Emergency Departments. Despite this common need, there is still a lack of options for adequate and safe analgesia and sedation in children. The objective of this study was to evaluate whether intranasal dexmedetomidine could provide more effective analgesia and sedation during a procedure than intranasal esketamine.MethodsThis was a double-blind equally randomized (1:1) superiority trial of 30 children aged 1-3 years presenting to the Emergency Department with a laceration or a burn and requiring procedural sedation and analgesia. Patients were randomized to receive 2.0 mcg/kg intranasal dexmedetomidine or 1.0 mg/kg intranasal esketamine. The primary outcome measure was highest pain (assessed using Face, Legs, Activity, Cry, Consolability scale (FLACC)) during the procedure. Secondary outcomes were sedation depth, parents' satisfaction, and physician's assessment. Comparisons were done using Mann-Whitney U test (continuous variables) and Fisher's test (categorical variables).ResultsAdequate analgesia and sedation were reached in 28/30 patients. The estimated sample size was not reached due to changes in treatment of minor injuries and logistical reasons. The median (IQR) of highest FLACC was 1 (0-3) with intranasal dexmedetomidine and 5 (2-6.75) with intranasal esketamine, (p-value 0.09). 85.7% of the parents with children treated with intranasal dexmedetomidine were "very satisfied" with the procedure and sedation compared to the 46.2% of those with intranasal esketamine, (p-value 0.1). No severe adverse events were reported during this trial.ConclusionsThis study was underpowered and did not show any difference between intranasal dexmedetomidine and intranasal esketamine for procedural sedation and analgesia in young children. However, the results support that intranasal dexmedetomidine could provide effective analgesia and sedation during procedures in young children aged 1-3 years with minor injuries.Trial registrationEudra-CT 2017-00057-40, April 20, 2017. https://eudract.ema.europa.eu/.

Dataset Information

The antidepressant effect and safety of non-intranasal esketamine: A systematic review.

Background

Aims

Methods

Results

Conclusions

Publications

The antidepressant effect and safety of non-intranasal esketamine: A systematic review.

Similar Datasets

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