Clinical predictors of depressive symptom remission and response after racemic ketamine and esketamine infusion in treatment-resistant depression.

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide and most people do not achieve symptom remission. Treatment-resistant depression (TRD) is characterized by the failure of at least one adequate trial of a major class of antidepressant, with adequate time and dosage. We aimed to identify clinical predictors of depressive symptom remission and response 24 h and 7 days after racemic ketamine and esketamine infusions. METHODS: A randomized, double-blind, active-controlled, non-inferiority trial using ketamine and esketamine in TRD. Individuals diagnosed with MDD according to Diagnostic and Statistical Manual of Mental Disorders version IV and fulfilling TRD criteria were recruited from March 2017 to June 2018. Participants received a single subanesthetic dose of ketamine (0.5 mg/kg) or esketamine (0.25 mg/kg) for 40 min. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and symptom remission was defined as a MADRS score ≤7 and response defined as ≥50% reduction in depressive symptom severity, 24 h and 7 days after the infusion. Clinical variables were selected based on previous clinical trials. Stepwise backward logistic regression was used, considering a confidence level of 95%. RESULTS: 61 subjects were included: 39 (63.9%) were females with a mean age of 47.2 ± 14.9. Higher number of therapeutic failures (Odds Ratio (OR) = 0.677; 95% confidence interval (CI): 0.47-0.97) and higher severity of illness (OR = 0.912; 95% CI: 0.83-0.99) were associated with fewer remissions of depressive symptoms 7 days after intervention, and with fewer response in 24 h (OR = 0.583; 95% CI: 0,40; 0,84 and OR = 0.909; 95% CI: 0,83; 0,99, respectively). CONCLUSION: Number of treatment failures and severity of illness were predictors of fewer remissions and responses of depressive symptoms in this TRD population. Study of predictors of remission may contribute to better selection patients that may benefit from receiving ketamine.

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 impulsiveness and risk behaviors among infected individuals with hepatitis C virus and human T-cell lymphotropic virus type 1.

INTRODUCTION AND OBJECTIVES: Hepatitis C virus (HCV) and human T-cell lymphotropic virus type 1 (HTLV-1) infections have chronic courses. HCV is primarily transmitted via the hematogenous route, whereas HTLV-1 is primarily transmitted sexually, although it can also be transmitted by blood. Individuals chronically infected with either HTLV-1 or HCV can differ in terms of behavioral characteristics and personality traits. This study compared the occurrence of risk behaviors and impulsivity aspects between HCV and HTLV-1 carriers. MATERIALS AND METHODS: Observational, comparative and cross-sectional study that involved a sample of outpatients who had HCV or HLTV-1, by way of a sociodemographic and behavioral questionnaire and the Barratt Impulsiveness Scale - BIS-11. 143 individuals with HCV and 113 individuals with HTLV-1 were evaluated. RESULTS: There was a difference with regards to gender among patients, with mostly males affected in the HCV group. Risk behaviors commonly mediated by impulsiveness were significantly more frequent in the HCV group. Similarly, overall impulsiveness and domain nonplanning were higher in the HCV group. Multivariate analysis showed that increased age, male gender, higher nonplanning scores and HCV infection were independent factors for the occurrence of risk behaviors. Both groups presented high rates of other sexually transmitted diseases and a low rate of condom use in sexual relations. CONCLUSIONS: This study confirms the higher rate of risk behaviors and the levels of impulsiveness commonly observed in patients with HCV, along with comparisons to patients with HTLV-1.

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.

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.

Significações atribuídas por portadores de visão monocular à perda visual e cirurgia de catarata / Significations imputed by monocular vision careers to visual loss and cataract surgery

Objetivo: Identificar percepções e significados referentes à perda visual de pacientes que apresentavam visão monocular e diagnóstico de catarata, com indicação cirúrgica, por comprometimento visual significativo. Métodos: Desenvolveu-se estudo qualitativo, por meio de entrevistas abertas, com 8 sujeitos identificados por Campanha da Catarata, realizada no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), em novembro de 2004. Resultados: Dos entrevistados, 4 eram do sexo feminino e 4 do sexo masculino, tendo a idade variado de 38 a 86 anos. Referiram atividades profissionais como responsáveis pela perda visual, apontaram dificuldades para conseguir o atendimento médico, manifestaram desconhecimento e crenças populares em relação ao próprio problema ocular e dificuldades encontradas no cotidiano em decorrência da doença. Conclusões: Foram identificados significados, percepções, sentimentos, reações e experiências relacionados à catarata e à perda visual. A ocorrência da catarata no único olho significou angústia e situação conflituosa relacionadas à perda da independência. A expectativa de voltar a enxergar mediante intervenção cirúrgica prendeu-se ao sentimento de ter uma vida “normal”, de sentir-se útil e do retorno ao mercado de trabalho.

Purpose: To identify perceptions and significations relating to the visual loss and the cataract surgery among monocular vision patients who present surgical indication by means of a impairment. Methods: A qualitative study through open interviews with 8 individuals identified by the Cataract Project, was conducted in Hospital das Clínicas, São Paulo University Medical School (HC-FMUSP), during November, 2004. Results: The study included 4 women and 4 men, ages from 38 to 86 years old. They reported professional activities as liable for the visual loss, pointed out difficulties to get medical care and revealed popular beliefs and insufficient knowledgea bout their own ocular problem. Conclusions: Meanings, perceptions, feelings, reactions and experiences were identified related to cataract and visual loss, in general attributed to their professional activity. The occurence of cataract in a single eye signified to them anguish andconflictive situation related to loss of independence. Expectancy of seeing again through surgical procedure became attached to the sense of having a normal and useful life and by the fact of returning to the labour market.

Atividade ocupacional e catarata senil - opinião de pacientes de hospital universitário / Occupational activity and senile cataract - opinions of patients of a university hospital

Objetivo: Identificar a situação ocupacional e percepções de portadores de catarata senil sobre a relação entre a atividade ocupacional exercida e o surgimento da doença. Métodos: Desenvolveu-se estudo observacional transversal descritivo, por meio de questionário estruturado, aplicado por entrevista, elaborado a partir de estudo exploratório. A amostra, prontamente acessível, foi formada por pacientes atendidos pelo setor de catarata da clínica oftalmológica de um hospital universitário. Resultados: A amostra foi constituída por 110 sujeitos de ambos os sexos (34,5 por cento homens; 65,5 por cento mulheres), com idade entre 43 e 89 anos mais ou menos 10,3 anos. A maior proporção dos entrevistados não exercia atividade remunerada (87,3 por cento). Dentre as opiniões acerca das causas da catarata, destacaram-se a velhice (69,1 por cento), o uso excessivo dos olhos (57,3 por cento) e a exposição ao calor nos olhos (40,9 por cento). Quanto à opinião sobre relação entre atividades profissionais exercidas e catarata, 56,4 por cento não acreditavam que o trabalho tivesse influído, enquanto 43,6 por cento atribuíram às atividades ocupacionais a essa afecção ocular. Foram atribuídos às atividades profissionais: o cansaço visual (37,5 por cento), contato com calor excessivo (12,5 por cento) e uso de produto químico (10,3 por cento). Conclusões: Evidenciou-se predominância acentuada de idosos de baixa escolaridade, não mais exercendo atividade ocupacional e inativos no mercado de trabalho. Entre os que exerciam, prevaleceram as ocupações manuais especializadas, o que sugere reduzido nível socioeconômico e baixo poder aquisitivo. Atribuíram como causas do comprometimento visual situações decorrentes de atividades ocupacionais, como o uso excessivo dos olhos e a exposição ao calor, evidenciando-se conhecimentos errôneos.