Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

Smith-Apeldoorn, Sanne Y; Veraart, Jolien K E; Kamphuis, Jeanine; Asselt, Thea van; Touw, Daan; Rot, Marije aan het; Schoevers, Robert A.

doi:10.1186/s12888-019-2359-1

Cited by 23 publications

(11 citation statements)

References 77 publications

(84 reference statements)

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“…However, no studies indicate that the antidepressant acute effects of ketamine are maintained in the long-term. Nevertheless, adverse events have been reported in different studies, and the IV formulation of ketamine may hamper its administration in several clinical settings [ 133 ]. In this framework, esketamine, the S-enantiomer of ketamine, has about a four-fold greater affinity for the glutamate receptor than ketamine, thus allowing the use of much lower doses and reducing the risk of dose-dependent dissociative symptoms associated with ketamine administration.…”

Section: Discussion and Expert Opinionmentioning

confidence: 99%

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

Caldiroli

Capuzzi

Tagliabue

et al. 2021

IJMS

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Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

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Section: Discussion and Expert Opinionmentioning

confidence: 99%

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

Caldiroli

Capuzzi

Tagliabue

et al. 2021

IJMS

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“…What is more, a study has been designed to investigate repeated administration of oral esketamine in patients with TRD. Therefore, we can study the advantages of different ways of treatment strategies of MDD in the future [13].…”

Section: Discussionmentioning

confidence: 99%

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials

Yang

Wang

et al. 2021

Psychiatr Q

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Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P < 0.00001), dizziness (RR = 3.00, 95% CI, 1.80 to 5.00, P < 0.0001), vertigo (RR = 7.47, 95% CI, 2.55 to 21.86, P = 0.0002), hypoesthesia (RR = 5.68, 95% CI, 2.06 to 15.63, P = 0.0008), sedation (RR = 3.96, 95% CI, 1.29 to 12.15, P = 0.02) and paresthesia(RR = 3.05, 95% CI, 1.07 to 8.65, P = 0.04)were significantly increased compared with placebo. Our synthesized data analysis revealed drug specific risk profiles. The most frequent adverse effects under treatment with esketamine were nausea, dissociation, dizziness, vertigo, hypoesthesia,sedation and paresthesia.

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“…Based on these findings, we decided to design a randomised controlled trial with a treatment duration of 6 weeks and monitoring of blood levels of (nor)ketamine. 35 If safety, tolerability and effectiveness are confirmed, oral esketamine could become a suitable treatment strategy for TRD.…”

Section: Discussionmentioning

confidence: 99%

Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study

et al. 2021

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Background Intravenous infusion of ketamine can produce rapid and large symptom reduction in patients with treatment-resistant depression (TRD) but presents major obstacles to clinical applicability, especially in community settings. Oral esketamine may be a promising addition to our TRD treatment armamentarium. Aims To explore the safety, tolerability and potential clinical effectiveness of a 3-week treatment with repeated, low-dose oral esketamine. Method Seven patients with chronic and severe TRD received 1.25 mg/kg generic oral esketamine daily, over 21 consecutive days. Scores on the Systematic Assessment for Treatment Emergent Events (SAFTEE), Community Assessment of Psychic Experiences (CAPE), Clinician Administered Dissociative States Scale (CADSS) and Hamilton Rating Scale for Depression (HRSD) instruments, as well as blood pressure and heart rate, were repeatedly assessed. Results Treatment with oral esketamine was well-tolerated. No serious side-effects occurred, and none of the participants discontinued treatment prematurely. Psychotomimetic effects were the most frequently reported adverse events. Mean HDRS score decreased by 16.5%, from 23.6 to 19.7. Three participants showed reductions in HDRS scores above the minimum clinically important difference (eight-point change), of whom two showed partial response. No participants showed full response or remission. Conclusions These results strengthen the idea that oral esketamine is a safe and well-tolerated treatment for patients with chronic and severe TRD, but therapeutic effects were modest. Results were used to design a randomised controlled trial that is currently in progress.

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Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

Cited by 23 publications

References 77 publications

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials

Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study

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