The effects of intranasal esketamine on on-road driving performance in patients with major depressive disorder or persistent depressive disorder.

BACKGROUND: Intranasal esketamine demonstrates rapid improvement of depressive symptoms. However, transient adverse effects (dissociation, sedation and dizziness) may occur, which could impact driving performance. AIMS: To evaluate the effects of 84 mg intranasal esketamine on driving performance in unipolar major depressive disorder (MDD) or persistent depressive disorder (PDD) patients. METHODS: The study consisted of two parts. Part A was a single-blind, double-dummy, randomized three-period, cross-over study to compare effects of esketamine versus placebo on next morning driving, 18 ± 2 h post-treatment. Alcohol was administered to demonstrate assay sensitivity. In Part B, same-day driving, 6 ± 0.5 hours post-treatment, was assessed during twice weekly esketamine administration for 3 weeks. Twenty-seven patients with mild-to-moderate MDD or PDD without psychotic features completed a 100 km on-the-road driving test on a public highway in normal traffic. The primary outcome was standard deviation of lateral position (SDLP; cm; weaving of car). RESULTS: In Part A, alcohol impaired driving performance compared to placebo: Least-square means (95% CI), p-value for delta SDLP (cm) compared with placebo: (ΔSDLP = + 1.83 (1.03; 2.62), p < 0.001), whereas esketamine did not: (ΔSDLP = -0.23 (-1.04; 0.58), p = 0.572). In Part B, weekly driving tests showed no differences between placebo baseline SDLP and after esketamine administration over 3 weeks: Day 11: (ΔSDLP = -0.96 (-3.72; 1.81), p = 0.493), Day 18: (ΔSDLP = -0.56 (-3.33; 2.20), p = 0.686) and Day 25: (ΔSDLP = -1.05 (-3.82; 1.71), p = 0.451). CONCLUSIONS: In this study, esketamine did not impair on-road driving performance the next morning following a single dose, or on same day after repeated administration.

Immune Responses after Heavy Alcohol Consumption: Cytokine Concentrations in Hangover-Sensitive and Hangover-Resistant Drinkers.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

The Association between Ethanol Elimination Rate and Hangover Severity.

Assessments in blood and saliva suggests that the amount of ethanol present in the first hours after alcohol consumption and into the following morning is associated with hangover severity. The current analysis determines how ethanol elimination rate is related to hangover severity reported throughout the day. n = 8 subjects participated in two studies. The first was a naturalistic study comprising an evening of alcohol consumption. Hangover severity was assessed hourly from 10 a.m. to 4 p.m., using a 1-item hangover severity scale ranging from 0 (absent) to 10 (extreme). The second study comprised a highly controlled alcohol challenge to reach a breath alcohol concentration (BrAC) of 0.05%. Breathalyzer tests were conducted every 5 min until BrAC reached zero. The ethanol elimination rate, expressed in BrAC%/hour, was computed by dividing the peak BrAC (%) by the time to BrAC of zero (h). At 11:00, 13:00, and 14:00, there were significant negative partial correlations, controlling for estimated BrAC, between ethanol elimination rate and hangover severity. The findings suggest that drinkers with a faster ethanol elimination rate experience less severe hangovers. The observations should be confirmed in a larger sample of subjects who participate in a single study that assesses both hangover severity and ethanol elimination rate.

Advantages and Limitations of Naturalistic Study Designs and their Implementation in Alcohol Hangover Research.

In alcohol hangover research, both naturalistic designs and randomized controlled trials (RCTs) are successfully employed to study the causes, consequences, and treatments of hangovers. Although increasingly applied in both social sciences and medical research, the suitability of naturalistic study designs remains a topic of debate. In both types of study design, screening participants and conducting assessments on-site (e.g., psychometric tests, questionnaires, and biomarker assessments) are usually equally rigorous and follow the same standard operating procedures. However, they differ in the levels of monitoring and restrictions imposed on behaviors of participants before the assessments are conducted (e.g., drinking behaviors resulting in the next day hangover). These behaviors are highly controlled in RCTs and uncontrolled in naturalistic studies. As a result, the largest difference between naturalistic studies and RCTs is their ecological validity, which is usually significantly lower for RCTs and (related to that) the degree of standardization of experimental intervention, which is usually significantly higher for RCTs. In this paper, we specifically discuss the application of naturalistic study designs and RCTs in hangover research. It is debated whether it is necessary to control certain behaviors that precede the hangover state when the aim of a study is to examine the effects of the hangover state itself. If the preceding factors and behaviors are not in the focus of the research question, a naturalistic study design should be preferred whenever one aims to better mimic or understand real-life situations in experimental/intervention studies. Furthermore, to improve the level of control in naturalistic studies, mobile technology can be applied to provide more continuous and objective real-time data, without investigators interfering with participant behaviors or the lab environment impacting on the subjective state. However, for other studies, it may be essential that certain behaviors are strictly controlled. It is, for example, vital that both test days are comparable in terms of consumed alcohol and achieved hangover severity levels when comparing the efficacy and safety of a hangover treatment with a placebo treatment day. This is best accomplished with the help of a highly controlled RCT design.

Mental resilience, perceived immune functioning, and health.

BACKGROUND: Mental resilience can be seen as a trait that enables an individual to recover from stress and to face the next stressor with optimism. People with resilient traits are considered to have a better mental and physical health. However, there are limited data available assessing the relationship between resilient individuals and their perspective of their health and immune status. Therefore, this study was conducted to examine the relationship between mental resilience, perceived health, and perceived immune status. METHODS: A total of 779 participants recruited at Utrecht University completed a questionnaire consisting of demographic characteristics, the brief resilience scale for the assessment of mental resilience, the immune function questionnaire (IFQ), and questions regarding their perceived health and immune status. RESULTS: When correcting for gender, age, height, weight, smoker status, amount of cigarettes smoked per week, alcohol consumption status, amount of drinks consumed per week, drug use, and frequency of past year drug use, mental resilience was significantly correlated with perceived health (r=0.233, p=0.0001), perceived immune functioning (r=0.124, p=0.002), and IFQ score (r=-0.185, p=0.0001). CONCLUSION: A significant, albeit modest, relationship was found between mental resilience and perceived immune functioning and health.

The breathtaking truth about breath alcohol readings of zero.

INTRODUCTION: It has been postulated that the hangover state starts when breath alcohol concentration is zero. METHODS: Data from 2 studies that assessed ethanol in breath, blood and urine were compared. RESULTS: The data revealed that ethanol may still be present in the blood and urine during the hangover state, despite breath analyser readings of zero. DISCUSSION: As ethanol is still present in the body despite zero breath alcohol readings, the current consensus to postpone cognitive testing in hangover studies until breath alcohol concentration is zero should be reconsidered.

Development of a Definition for the Alcohol Hangover: Consumer Descriptions and Expert Consensus.

Up to now, there is no adequate definition of the alcohol hangover. The purpose of the current study was to develop a useful definition, and consensus among those who will use it in scientific publications. A survey was conducted among N=1099 social drinkers who recently had a hangover. They were asked to provide their definition of the alcohol hangover. Text mining and content analysis revealed 3 potential definitions. These were submitted to members of the Alcohol Hangover Research Group, who were asked to give their expert opinion on the proposed definitions. Taking into account their comments and suggestions, the following definition for the alcohol hangover was formulated: "The alcohol hangover refers to the combination of mental and physical symptoms, experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration approaches zero."