Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine and esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial.

BACKGROUND: Ketamine and esketamine have both shown significant antidepressant effects in treatment-resistant depression (TRD), and conflicting evidence suggests that induced dissociation by these drugs can be a clinical predictor of esketamine/ketamine's efficacy. METHODS: This study is a secondary analysis from a bi-center, randomized, controlled trial. Participants were randomly assigned 1:1 to receive an IV infusion of esketamine (.25 mg/kg) or racemic ketamine (.50 mg/kg) over 40 minutes. Dissociative symptoms were assessed using the Clinician-Administered Dissociative State Scale (CADSS) 40 minutes following the beginning of the infusion. The variation in depression scores was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), which was administered before the intervention as a baseline measure and 24 hrs, 72 hrs, and 7 days following infusion. RESULTS: Sixty-one patients were included in the analysis. Examining CADSS scores of 15 or below, for every 1-point increment in the CADSS score, there was a mean change of -0.5 (SD = 0.25; p-value 0.04) of predicted MADRS score from baseline to 24 hrs. The results for 72 hrs and 7 days following infusion were not significant. Limitations: This study was not designed to assess the relationship between ketamine or esketamine-induced dissociation and antidepressant effects as the main outcome, therefore confounding variables for this relationship were not controlled. CONCLUSION: We suggest a positive relationship between dissociation intensity, measured by CADSS, and antidepressant effect 24 hours after ketamine and esketamine infusion for a CADSS score of up to 15 points.

Esketamine for Unipolar Major Depression With Psychotic Features: A Retrospective Chart Review and Comparison With Nonpsychotic Depression.

PURPOSES/BACKGROUND: The aims of the study were to assess subanesthetic esketamine as an antidepressant for major depressive disorder with psychotic features (PMDD) and to compare posttreatment symptoms among those with PMDD to a sample of nonpsychotic depression (major depressive disorder [MDD]). METHODS/PROCEDURES: This study is a retrospective chart review of patients with major depression and current psychotic symptoms, treated with a single parenteral 0.5-mg/kg dose of esketamine. Depression symptoms were assessed at baseline and 24-hour posttreatment with the Montgomery-Åsberg Depression Rating Scale. Individuals with PMDD were matched in a 1:2 ratio to nonpsychotic MDD patients from a randomized, noninferiority clinical trial of esketamine. FINDINGS/RESULTS: A total of 15 individuals with PMDD were included, which had higher baseline depression scores (PMDD = 40.9, MDD = 33.6, P = 0.004). A statistically significant change in depressive symptoms was found for the PMDD sample (ß = -16.20 [95% confidence interval, -23.30 to -9.10], P < 0.001), and no difference between PMDD and MDD groups was observed in the matched-sample analysis (ß = -2.2 [95% confidence interval, -9.32 to 4.58], P = 0.537). Treatment-induced dissociative symptoms were present for both groups, self-contained to within 2 hours after treatment, and no exacerbation of psychotic symptoms was found in clinical assessments. IMPLICATIONS/CONCLUSIONS: Results suggest a single 0.5-mg/kg dose of esketamine may benefit individuals with PMDD, and the symptom reduction may be comparable with esketamine's effects for MDD. Furthermore, esketamine may induce an antidepressant response in those with PMDD without complication of psychotic symptoms. Future research with controlled designs is warranted.

Trait dissociation as a predictor of induced dissociation by ketamine or esketamine in treatment-resistant depression: Secondary analysis from a randomized controlled trial.

Dissociative symptoms are common, possibly severe, side effects associated with the use of ketamine and esketamine in depression. We investigated the relationship between trait dissociation and dissociation induced by ketamine and esketamine used as augmentation therapy in treatment-resistant depression (TRD). Adults with TRD were randomly assigned to receive a single intravenous infusion, with a duration of 40 min, of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg. We assessed trait dissociation with the Dissociative Experience Scale (DES) and, to evaluate induced dissociation, the Clinician-Administered Dissociative States Scale (CADSS) was used. Thirty-two subjects received esketamine and 29 received ketamine. The groups had similar median DES scores (p = 0.26). More than 30% of the patients in both groups had DES scores ≥30 points. The median CADSS score in the esketamine group was equivalent to that in the ketamine group (p = 0.40). Every 5 points increment in the DES was associated with a 10.9% (95% CI 4.5-17.8%) increase in the CADSS, in an exponential fashion when the two groups were pooled together. Subjects with high trait dissociation had a higher risk of induced dissociation state (relative risk [RR] 1.41, 95% CI 1.11-1.78) and very high induced dissociation (RR 3.05, 95% CI 1.14-8.15). Induced dissociation was not a serious adverse effect. The findings suggest that trait dissociation is a predictor of induced dissociation by Ketamine or Esketamine in TRD subjects. Screening for trait dissociation and counseling patients with high trait dissociation on the risks of dissociation by these drugs are recommended.

Intravenous arketamine for treatment-resistant depression: open-label pilot study.

We aimed to analyze the efficacy and safety of arketamine, the R(-)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6-27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.

Comparative study of esketamine and racemic ketamine in treatment-resistant depression: Protocol for a non-inferiority clinical trial.

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.

Compressive strength of glass ionomer cements used for atraumatic restorative treatment / Resistência à compressão de cimentos de ionômero de vidro utilizados no tratamento restaurador atraumático

Purpose: This study evaluated the compressive strength of five glass ionomer cements (Ketac Molar, Fuji IX, Magic Glass, Vidrion R, and Vitro Molar) as a function of storage period (1 hour and 24 hours). Methods: Sixteen specimens of each material were fabricated according to ISO/DP #7489 Specification using a 6x12 mm (diameter and height) matrix. After setting, specimens were stored in distilled water at 37 ºC. Eight specimens per cement were subjected to the compressive strength test in a universal testing machine after 1 hour, and the other eight specimens were tested after 24 hours. Data were analyzed by ANOVA and Tukey's test (α=5%). Results: The compressive strength mean values (kgf) after 1 and 24 hours were: Ketac Molar: 218.75 and 297.88; Fuji IX: 335.75 and 350.88; Magic Glass: 61.50 and 140.13; Vidrion R: 142.38 and 230.88; and Vitro Molar: 183.38 and 297.50. After 1 hour Fuji IX had the highest compressive strength. All materials but Fuji IX showed higher compressive strength in 24 hours than in 1 hour. After 24 hours, no significant differences were found among Fuji IX, Ketac Molar, and Vitro Molar. Magic Glass had the lowest compressive strength in both storage periods. Conclusion: Fuji IX showed the best results after 1 hour. After 24-hour storage, Fuji IX, Ketac Molar, and Vitro Molar had similar performance.

Objetivo: Este estudo avaliou a resistência à compressão de 5 cimentos de ionômero de vidro (Ketac Molar, Fuji IX, Vitro Molar, Magic Glass e Vidrion R), em dois tempos de armazenagem (1 h e 24 h). Metodologia: Foram confeccionados 16 corpos-de-prova (CP) para cada material (n=8), seguindo as especificações da ISO/DP 7489. Os materiais foram manipulados e inseridos numa matriz desmontável (6 mm de diâmetro e 12 mm de altura). Após a presa os CP foram armazenados em água destilada a 37 ºC. Metade dos CP de cada material foi submetida a ensaio de compressão após 1 h e a outra metade foi testada após 24 h. Os resultados foram analisados por ANOVA e teste de Tukey (α=5%). Resultados: Os valores médios de resistência à compressão (kgf) após 1 h e 24 h foram: Ketac Molar: 218,75 e 297,88; Fuji IX:335,75 e 350,88; Magic Glass:61,50 e 140,13; Vidrion R:142,38 e 230,88, e Vitro Molar:183,38 e 297,50. Em 1 h o Fuji IX apresentou a maior resistência à compressão. Com exceção do Fuji IX, todos os ionômeros apresentaram maior resistência em 24h do que em 1 h. Em 24 h não houve diferença entre Fuji IX, Ketac Molar e Vitro Molar. O cimento Magic Glass apresentou os menores valores nos 2 tempos. Conclusão: O cimento Fuji IX apresentou os melhores resultados após 1 h. Após 24 h de armazenamento, Fuji IX, Ketac Molar e Vitro Molar tiveram desempenho similar.

Efeito do tempo de condicionamento da superfície cerâmica sobre a resistência / Effect of the conditioning time of the ceramic surface on bond strength between a fluorapatite ceramic and a resin cement

O objetivo deste estudo foi avaliar a resistência de união entre uma cerâmica sintética de fluorapatita e leucita livre de feldspato e um cimento resinoso dual, variando o tempo de condicionamento ácido da superfície da cerâmica. Foram confeccionados 16 blocos de cerâmica (IPS d. SIGN- Ivoclar-Vivadent) que foram divididos aleatoriamente em 2 grupos (n=8), conforme o tempo de condicionamento ácido da superfície cerâmica: G1 - condicionamento durante 30 segundos com ácido fluorídrico 10%, seguido da aplicação do agente silano (Primer ceramic, 3M/Espe); G2: condicionamento com ácido fluorídrico 10% durante 2 minutos, seguido da aplicação do silano (Primer ceramic, 3M/Espe). Os blocos de cerâmica foram unidos a blocos de resina composta, recém confeccionados, (Fill Magic, Vigodent) com o cimento resinoso Rely X (3M/Espe) sob uma carga de 750g. Os conjuntos foram armazenados em água por 24h e seccionados em dois eixos, x e y, obtendo-se corpos-de-prova (CP) com área de aproximadamente 0,7 mm2. Os CP foram submetidos ao ensaio de microtração a uma velocidade de 0,5 mm/min. Os resultados foram submetidos a duas análises estatísticas utilizando todos os CP, incluindo os com valores zero (G1 = 12,99 ± 6,7 MPa e G2 = 14,97 ± 3,7 MPa) e excluindo os com valores zero (G1 = 20,19 ± 3,8 MPa e G2 = 22,31 ± 2,8 MPa). Não foi observada diferença estatística entre os grupos em nenhuma das análises (p>0,05).