Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study.

BACKGROUND: Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and/or IN routes. METHODS: In this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). RESULTS: At the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed, assessed by Montgomery-Åsberg Depression Rating Scale. Moreover, the self-reported depressive symptoms, as measured by the Beck Depression Inventory II (BDI-II), significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations (BDI-II) up to the sixth month consistently showed scores lower than the baseline. LIMITATIONS: The small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. CONCLUSIONS: This groundbreaking study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained antidepressant effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Rapid and long-lasting effects of subcutaneous esketamine on suicidality: An open-label study in patients with treatment-resistant depression.

Therapeutics for suicide management is limited, taking weeks to work. This open-label clinical trial with 18 treatment-resistant depressive patients tested subcutaneous esketamine (8 weekly sessions) for suicidality. We noted a rapid and enduring effect of subcutaneous esketamine, lasting from one week to six months post-treatment, assessed by the Beck Inventory for Suicidality (BSI). There was an immediate drop in suicidality, 24 h following the initial dose, which persisted for seven days throughout the eight-week dosing period. Additionally, this study is the first to examine a six-month follow-up after multiple administrations of subcutaneous esketamine, finding consistently lower levels of suicidality throughout this duration. Conversely, suicidality also was measured along the 8-weeks of treatment by a psychiatrist using the Montgomery-Asberg Depression Rating Scale (MADRS), which showed significant reduction only after two treatment sessions expanding until the last session. Moreover, notably, 61% of patients achieved remission on suicidality (MADRS). These results suggest that weekly subcutaneous esketamine injections offer a cost-effective approach that induces a rapid and sustained response to anti-suicide treatment. This sets the stage for further, more controlled studies to corroborate our initial observations regarding the effects of SC esketamine on suicidality. Registered trial at: https://ensaiosclinicos.gov.br/rg/RBR-1072m6nv.

Drugs age-of-onset as a signal of later post-traumatic stress disorder: Bayesian analysis of a census protocol.

Individuals with PTSD have an increased risk of drug use disorders. Conversely, we aim to evaluate how early onset of alcohol, tobacco and psychoactive drugs use are associated with PTSD later in life. 2,193 brazilian young adults completed modularized assessments: The Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist-Civilian Version (PCL-C, transformed to PCL-5 through a crosswalk procedure), the Barratt Impulsivity Scale; and a survey on drug use with self-report questions about first use, current use, frequency, quantity, and interpersonal consequences. Bayesian inference and multivariate regression models were used to examine the effects on the risk of PTSD, considering different assumptions of information flow. Raw and unbiased (multivariate) estimates consistently revealed that earlier age of onset of alcohol and tobacco use increased risk for PTSD (Odds-ratios between 2.39 and 3.19 (Alcohol) and 1.82 to 2.05 (Tobacco). Among those who had PTSD (310), 10.3% (32) were very precocious at the onset age (12 to 18 years) of alcohol consumption (No-PTSD: 89 out 1883, 4.7%). Data supports a model in which age of onset effects are partially mediated by the number of trauma exposures. Early intoxication might suggest vulnerability for qualifying trauma events, or it may increase chances of exposure. Also, PTSD may be more likely to occur among trauma-exposed individuals with early intoxicating experiences due to alcohol or drug self-administration. The last possibility resonates with the idea that early intoxication might disrupt adolescent brain development, with a subsequent reduction in resilience when qualifying trauma events occur.

Impulsivity is relevant for trauma exposure and PTSD symptoms in a non-clinical population.

Impulsivity is a relevant construct for explaining both normal individual differences in personality and more extreme personality disorder, and is often investigated within clinical populations. This study aims to explore the college students' impulsivity patterns and to investigate the association across levels of impulsivity with trauma exposure and PTSD development in a non-clinical population. A one-phase census survey of seven college institutions assessed 2213 students in three metropolitan regions of Northeastern Brazil. All subjects anonymously completed a self-applied protocol consisting of: a socio-demographic questionnaire, Trauma History Questionnaire (THQ), PTSD Checklist (PCL-C), and Barratt Impulsiveness Scale (BIS-11). The median for frequency of trauma exposure was 4 events for people with low and normal impulsivity, and 6 for highly impulsive ones. Individuals with higher impulsivity presented earlier exposition than non-impulsive ones, and worst outcome: 12.4% with PTSD, against 8.4% and 2.3% (normal and low impulsivity). Of the three factors of impulsivity, the Attentional factor conferred the strongest association with PTSD development. Results suggest that impulsivity is also a relevant trait in a non-clinical population and is associated with trauma exposure and PTSD. Strategies to promote mental health in adolescents may be pertinent, especially with the aim of managing impulsivity.

Prevention of posttraumatic stress disorder with propranolol: A meta-analytic review.

OBJECTIVE: PTSD is associated with significant morbidity and its prevention could reduce a significant burden of individual and societal suffering. The aim of this study is to conduct a systematic review of the literature on the prevention of PTSD by using propranolol following exposure to a traumatic event. METHODS: Authors searched all studies published in the MEDLINE database up to November 2014 and reviewed textbooks and reference lists. Authors of relevant articles were contacted. Clinical trials and observational studies were included if they investigated the effect of propranolol in the acute post-trauma phase to prevent PTSD symptoms for subjects 18 years of age or older. PTSD was diagnosed according to DSM or widely accepted and validated diagnostic tools. A random-effects model was used to perform meta-analysis. RESULTS: Five studies were included in the review for meta-analysis. Heterogeneity was not significant (τ2=0.0, S.E=0.247; Cochran's Q(4)=1.870, p=0.760; I2=0%). Relative risk point estimate to the effect of propranolol to prevent PTSD was 0.92 (95% CI: 0.55-1.55). Asymmetry was not significant under the Egger test (z=-1.34; p=0.180). CONCLUSIONS: The findings suggest that propranolol treatment after the traumatic event did not alter the incidence of PTSD, although physiological responses are generally attenuated. The studies included small sample sizes, which can preclude the detection of significant results. Authors believe future studies should achieve larger sample sizes and longer follow-up periods.

Hepatitis C virus infection as a traumatic experience.

OBJECTIVE: The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS: We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS: Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (ß: -24.85; 95% CI: -42.08; -7.61), Bodily Pain (ß: -19.36; 95% CI: -31.28; -7.45), General Health (ß: -20.79; 95% CI: -29.65; -11.92), Vitality (ß: -11.92; 95% CI: -20.74; -3.1), Social Functioning (ß: -34.73; 95% CI: -46.79; -22.68), Role-Emotional (ß: -26.07; 95% CI: -44.61; -7.53), Mental Health (ß: -17.46; 95% CI: -24.38; -10.54). CONCLUSION: HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.

Clinical and socio-demographic characteristics of college students exposed to traumatic experiences: a census of seven college institutions in Northeastern Brazil.

BACKGROUND: Epidemiological studies show that most of the adult population will be exposed to at least one potentially traumatic event in the course of his/her life; adolescence and early adulthood are the most vulnerable periods of life for exposure to traumatic experiences (70% of their deaths are due to external causes). Posttraumatic Stress Disorder is characterized by the development of dysfunctional symptoms that cause distress or social, academic, or occupational impairment, as result of exposure to a traumatic event. The aim of this multicentric study is to establish the proportion of college students, within seven institutions in Northeastern Brazil, who were exposed to traumatic experience and met PTSD criteria. METHODS/DESIGN: A one-phase census protocol of seven college institutions in three metropolitan regions in Northeastern Brazil was performed (April to July 2011). All students aged 18 years or older, matriculated and attending their first or final semester were eligible. The self-applied protocol consisted of a socio-demographic questionnaire and the following scales adjusted to Brazilian Portuguese standards Trauma History Questionnaire (THQ), PTSD Checklist-Civilian (PCL-C), Impulsivity Scale (BIS-11). Data were entered into SPSS 17.0. RESULTS: 2213 (85.5%) students consented to participate, and completely filled in the protocols. Of these, 66.1% were woman, mean age 23.9 (SD 6.3), 82.7% were single, and 57.3% attended university outside their native cities. The total PTSD prevalence was 14%, and the median for frequency of trauma exposure was 5 events. CONCLUSION: A high frequency of exposure to violence, as well as a high rate of PTSD, suicide attempts, and high-risk sexual behavior was found in Brazilian college students. This highlights the importance of effective public health actions in relation to the prevention and treatment of PTSD and other dysfunctional behaviors resulting from traumatic exposure in young individuals, usually an at risk population for violence and traumatic situations.

Post-traumatic stress disorder as a comorbidity: impact on disease outcomes.

Post-traumatic stress disorder (PTSD) is associated with many psychiatric and nonpsychiatric comorbidities. Growing evidence suggests that PTSD as a comorbidity may impair drug adherence, quality of life and sleep quality, as well as increase rehospitalization rates, disease relapses, intensity of symptoms, morbidity and mortality. The aim of this article is to examine the literature regarding the effects of PTSD comorbidity on physical and mental health.