An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers.

BACKGROUND: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day. METHODS: The study had a semi-naturalistic design. In the evening before the test days, participants were not supervised. They could drink ad libitum drinking on the alcohol test day and refrained from drinking alcohol on the control day. Activities and behaviors on the alcohol and control day were reported the follow morning. On both test days, from 09:30 to 15:30, hourly assessments of immune fitness (single-item scale) and overall hangover severity (single-item scale) were made and saliva samples were collected for biomarker assessments. RESULTS: N = 14 hangover-resistant drinkers and n = 15 hangover-sensitive drinkers participated in the study. The amount of alcohol consumed on the alcohol day did not significantly differ between the hangover-resistant group (mean (SD) of 13.5 (7.9) alcoholic drinks) and the hangover-sensitive group (mean (SD) of 12.4 (4.4) alcoholic drinks). All hangover-sensitive drinkers reported having a hangover following the alcohol day (overall hangover severity score 6.1 (on a 0-10 scale) at 09:30, gradually decreasing to 3.3 at 15:30), whereas the hangover-resistant drinkers reported no hangover. On the control day, immune fitness of the hangover-sensitive group was significantly poorer than the hangover-resistant group. On the alcohol day, both groups showed a significant reduction in immune fitness. The effect was evident throughout the day, but significantly more pronounced in the hangover-sensitive group than the hangover-resistant group. No significant differences between the groups were found at any time point on the two test days for saliva concentrations of Interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α. CONCLUSIONS: Whereas hangover-sensitive drinkers reported a hangover following an alcohol day and hangover-resistant drinkers did not, both groups reported significantly reduced immune fitness throughout the day. However, the reduction in immune fitness among hangover-sensitive drinkers was significantly more pronounced in comparison to the hangover-resistant group.

Differences in Next-Day Adverse Effects and Impact on Mood of an Evening of Heavy Alcohol Consumption between Hangover-Sensitive Drinkers and Hangover-Resistant Drinkers.

The combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero, are collectively referred to as the alcohol hangover. Previous research revealed that 10 to 20% of drinkers claim not to experience next-day hangovers. Past studies were usually limited to single timepoint assessments. The aim of the current semi-naturalistic study was to compare the next-day effects of an evening of alcohol consumption of self-reported hangover-resistant drinkers (n = 14) with those of a group of self-reported hangover-sensitive drinkers (n = 15) at hourly timepoint throughout the day (09:30 until 15:30). Assessments of 23 hangover symptoms, mood (Profiles of Mood States-Short Form), and daytime sleepiness (Karolinska Sleepiness Scale) were made hourly after both an alcohol day and an alcohol-free control day. Additional morning assessments were made for mood (State-Trait Anxiety Inventory-Y, Beck's Depression Inventory-II), risk-taking behavior (RT-18), past night sleep (Groningen Sleep Quality Scale), alcohol consumption, and activities during the test days. No significant differences were found regarding the amount of alcohol consumed and the total sleep time of the two groups. The hangover-sensitive group reported having a hangover as well as the presence of a variety of hangover-related symptoms, which were most severe in the morning and then gradually decreased during the day. The most frequently reported and most severe symptoms were sleepiness and fatigue, concentration problems, and headache. In contrast, the hangover-resistant group reported the absence of a hangover and the presence and severity of next-day symptoms did not significantly differ from the control day, except for increased fatigue and reduced vigor. The next-day effects on sleepiness-related complaints and vigor were significantly more pronounced among hangover-sensitive drinkers compared to hangover-resistant drinkers. In conclusion, contrary to hangover-resistant drinkers, hangover-sensitive drinkers report a variety of hangover symptoms that gradually ease during the day, but are still present in the afternoon.

Immune Fitness and the Psychosocial and Health Consequences of the COVID-19 Pandemic Lockdown in The Netherlands: Methodology and Design of the CLOFIT Study.

This article provides an overview of the design and methodology of the "Corona lockdown: how fit are you?" (CLOFIT) study, including the questionnaires and scales that were included in the online survey. The aim of the CLOFIT study was to investigate the psychosocial and health consequences of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands. The survey was conducted among the Dutch population to collect data on immune fitness and the psychological and health consequences of the 2019 coronavirus disease (COVID-19) pandemic lockdown in the Netherlands. The CLOFIT dataset contains measures from N = 1910 participants and is broadly representative of the Dutch general population. The dataset represents both sexes, a range of ages including the elderly, different education levels, and ethnic backgrounds. The cohort also includes people with a diverse health status and range of medication use.

The 5HTOL/5HIAA Ratio as a Biomarker of Alcohol Hangover.

Assessment of the presence and severity of alcohol hangovers relies on the subjective method of self-report. Therefore, there is a need of adequate biomarkers that (1) correlate significantly with hangover severity, and (2) correspond to the level of hangover-related performance impairment objectively. In this naturalistic study, n = 35 social drinkers participated. Urine samples were obtained the morning after alcohol consumption and after an alcohol-free control day. Concentrations of 5-hydroxytryptophol (5-HTOL), 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HTOL/5-HIAA ratio were determined. The results confirm previous findings that 5-HTOL and the 5HTOL/5-HIAA ratio are useful biomarkers of recent alcohol consumption. Significant correlations were found with the amount of alcohol consumed, total drink time, and estimated BAC. However, urine concentrations of 5-HTOL and 5-HIAA (and their ratio 5HTOL/5-HIAA) did not significantly correlate with hangover severity. In conclusion, urine 5-HTOL, 5-HIAA, and the 5HTOL/5-HIAA ratio cannot be considered to be suitable biomarkers of alcohol hangover.

An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users.

OBJECTIVE: Previous research reported cognitive and psychomotor impairments in long-term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. METHODS: Neurocognitive and on-road driving performance of 19 long-term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self-reported use, exceeding the therapeutic threshold (CBZRA +), and 31 long-term regular BZRA users below (CBZRA -), was compared to that of 76 controls. RESULTS: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self-reported clinical complaints, was a significant covariate. Road-tracking performance was explained by CBZRA only. The CBZRA  + group exhibited increased mean standard deviation of lateral position comparable to that at blood-alcohol concentrations of 0.5 g/L. CONCLUSIONS: Functional impairments in long-term BZRA users are not attributable to self-reported clinical complaints or estimated BZRA concentrations, except for road-tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long-term BZRA users.

The Impact of Mood and Subjective Intoxication on Hangover Severity.

The aim of this study was to investigate whether baseline mood and/or mood while drinking have an impact on alcohol hangover severity. A survey was held among N = 331 young adults (mean age = 23.6 years, range = 18-35 years). Demographics, alcohol consumption, subjective intoxication, and hangover severity were assessed for the past three days. In addition, mood (baseline, while drinking, and during hangover) was also assessed. N = 143 participants reported to be hungover on the day of assessment, N = 122 participants reported to have been hungover the previous day ('yesterday'), and N = 87 participants reported to have been hungover two days before the assessment ('2 days ago'). The analyses revealed that baseline mood and mood while drinking had no relevant effect on the amount of consumed alcohol and did not significantly contribute to hangover severity. However, hangover severity was associated with significantly increased negative affect, particularly with higher levels of subjective stress on the day of the hangover.

The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover.

An increasing number of studies are focusing on the inflammatory response to alcohol as a potentially important determinant of hangover severity. In this article, data from two studies were re-evaluated to investigate the relationship between hangover severity and relevant biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol. Hangover severity was significantly and positively correlated with blood concentrations of biomarkers of the inflammatory response to alcohol, in particular, Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). At 4 h after alcohol consumption, blood ethanol concentration (but not acetaldehyde) was significantly and positively associated with elevated levels of IL-6, suggesting a direct inflammatory effect of ethanol. In addition, biomarkers of oxidative stress, i.e., malondialdehyde and 8-isoprostrane, were significantly correlated with hangover severity, suggesting that oxidative stress also contributes to the inflammatory response. The timing of the assessments suggests initial slow elimination of ethanol in the first hours after alcohol consumption. As a consequence, more ethanol is present in the second half of the night and the next morning, which will elicit more oxidative stress and a more profound inflammatory response. Together, these processes result in more severe hangovers.

Perceived Immune Fitness, Individual Strength and Hangover Severity.

Various factors may contribute to alcohol hangover severity. The purpose of the current investigation was to evaluate the possible impact of alcohol consumption patterns, perceived immune status, and baseline fatigue on hangover severity. A survey was completed by a convenience sample of N = 199 Dutch students who reported on their latest past month's heavy drinking occasion, including subjective intoxication (perceived drunkenness) and next-day hangover severity, which were rated on single-item scales ranging from 0 (absent) to 10 (extreme). In addition, perceived (momentary) immune fitness was assessed, and the Checklist Individual Strength (CIS) was completed to assess baseline fatigue. The analysis revealed that instead of the amount of alcohol consumed or estimated blood alcohol concentration, it appeared that subjective intoxication (i.e., level of drunkenness) was the most important determinant of alcohol hangover severity. Especially in men, albeit modest, it was perceived that immune fitness also significantly contributed to the level of hangover severity experienced.

Updating the Definition of the Alcohol Hangover.

In 2016, the Alcohol Hangover Research Group defined the alcohol hangover as "the combination of mental and physical symptoms experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration (BAC) approaches zero". In the light of new findings and evidence, we carefully reviewed the different components of that definition. Several studies demonstrated that alcohol hangovers are not limited to heavy drinking occasions. Instead, data from both student and non-student samples revealed that at a group level, alcohol hangover may occur at much lower BAC levels than previously thought. Regression analysis further revealed that for individual drinkers, the occurrence of hangovers is more likely when subjects consume more alcohol than they usually do. However, hangovers may also occur at a drinker's usual BAC, and in some cases even at lower BAC (e.g. in case of illness). We also carefully reviewed and modified other parts of the definition. Finally, hangovers are not necessarily limited to the 'next day'. They can start at any time of day or night, whenever BAC approaches zero after a single dinking occasion. This may also be on the same day as the drinking occasion (e.g. when drinking in, or until the morning and subsequently having a hangover in the afternoon or evening). To better reflect the new insights and sharpen the description of the concept, we hereby propose to update the definition of the alcohol hangover as follows: "The alcohol hangover refers to the combination of negative mental and physical symptoms which can be experienced after a single episode of alcohol consumption, starting when blood alcohol concentration (BAC) approaches zero", and recommend to use this new definition in future hangover research.

The Assessment of Overall Hangover Severity.

The aim of this study was to critically evaluate and compare the different methods to assess overall hangover severity. Currently, there are three multi-item hangover scales that are commonly used for this purpose. All of them comprise a number of hangover symptoms for which an average score is calculated. These scales were compared to a single, 1-item scale assessing overall hangover severity. The results showed that the hangover symptom scales significantly underestimate (subjective) hangover severity, as assessed with a 1-item overall hangover severity scale. A possible reason for this could be that overall hangover severity varies, depending on the frequency of occurrence of individual symptoms included in the respective scale. In contrast, it can be assumed that, when completing a 1-item overall hangover scale, the rating includes all possible hangover symptoms and their impact on cognitive and physical functioning and mood, thus better reflecting the actually experienced hangover severity. On the other hand, solely relying on hangover symptom scales may yield false positives in subjects who report not having a hangover. When the average symptom score is greater than zero, this may lead to non-hungover subjects being categorized as having a hangover, as many of the somatic and psychological hangover symptoms may also be experienced without consuming alcohol (e.g., having a headache). Taken together, the current analyses suggest that a 1-item overall hangover score is superior to hangover symptom scales in accurately assessing overall hangover severity. We therefore recommend using a 1-item overall hangover rating as primary endpoint in future hangover studies that aim to assess overall hangover severity.

Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover.

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their "normal" drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their "regular" drinking level, considerably higher alcohol intake-irrespective of the absolute amount-may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.

Driving performance and neurocognitive skills of long-term users of benzodiazepine anxiolytics and hypnotics.

OBJECTIVE: The aim of this study is to compare actual driving performance and skills related to driving of patients using benzodiazepine anxiolytics or hypnotics for at least 6 months to that of healthy controls. METHODS: Participants were 44 long-term users of benzodiazepine and benzodiazepine-related anxiolytics (n = 12) and hypnotics (n = 32) and 65 matched healthy controls. Performance was assessed using an on-the-road driving test measuring standard deviation of lateral position (SDLP, in cm) and a battery of neurocognitive tasks. Performance differences between groups were compared with a blood alcohol concentration of 0.5 mg/ml to determine clinical relevance. RESULTS: Compared with controls, SDLP was significantly increased in hypnotic users (+1.70 cm) but not in anxiolytic users (+1.48 cm). Anxiolytic and hypnotic users showed significant and clinically relevant impairment on neurocognitive task measuring executive functioning, vigilance, and reaction time. For patients using hypnotics for at least 3 years, no significant driving impairment was observed. CONCLUSION: Impairing effects of benzodiazepine hypnotics on driving performance may mitigate over time following longer term use (i.e. 3 years or more) although neurocognitive impairments may remain.

The Association between Alcohol Hangover Frequency and Severity: Evidence for Reverse Tolerance?

Although hangover is a common consequence of heavy alcohol consumption, the area is heavily under-researched. Hangover frequency is a potential predictor of future alcohol use disorder that may be affected by hangover severity, yet the relationship between hangover frequency and severity has not been investigated. Using different methodologies and assessment instruments, two surveys, and one naturalistic study collected data on hangover frequency, hangover severity, and alcohol consumption. The relationship between hangover frequency and severity was investigated via correlational analysis, considering potentially moderating variables including alcohol intake, estimated blood alcohol concentration, demographics, and personality characteristics. In all the three studies, a positive and significant association between hangover frequency and severity was found, which remained significant after correcting for alcohol intake and other moderating factors. These findings suggest that hangover severity increases when hangovers are experienced more frequently and may be driven by sensitization or reverse tolerance to this aspect of alcohol consumption. Future research should further investigate the relationship between hangover frequency and severity and alcohol use disorder and its implications for prevention.

Impact of mental resilience and perceived immune functioning on the severity of alcohol hangover.

OBJECTIVE: Recent research comparing hangover sensitive drinkers with hangover resistant drinkers has revealed that experiencing alcohol hangovers is associated with significantly poorer self-reported immune functioning (p < 0.0001). No significant difference between the groups was found on mental resilience. The objective of the current survey was to examine the association between hangover severity, perceived immune status, and mental resilience. N = 341 Dutch students, all hangover sensitive drinkers, completed an online survey. The Brief Resilience Scale was completed, and perceived immune functioning and overall hangover severity for their latest past month hangover were assessed. RESULTS: Students consumed a mean (SD) of 12.3 (5.9) alcoholic drinks the evening before their latest hangover. A significant positive association was found between mental resilience and perceived immune functioning (r = 0.372, p = 0.000). No significant associations of hangover severity were found with mental resilience (r = - 0.010, p = 0.858), or perceived immune functioning (r = - 0.025, p = 0.645). Previous research revealed that hangover resistant and hangover sensitive drinkers report having significantly different levels of immune functioning, and that the immune system is involved in the development of alcohol hangover. These findings suggest that levels of mental resilience and perceived immune functioning are not related to the severity of hangovers in hangover sensitive drinkers.

Inclusion and Exclusion Criteria of Clinical Trials for Insomnia.

Randomized controlled trials (RCTs) have eligibility criteria for the inclusion of participants. Ideally, the RCT sample would be representative for the patient population that will use the drug under investigation. However, external validity may be at stake when applying too many or too restrictive eligibility criteria. The current two-part study examined (1) the currently applied eligibility criteria in Phase II and III RCTs examining sleep medication; (2) how these criteria match with the insomnia population as a whole; and (3) how inclusion rates can be changed by an adaptation of these criteria. In the first study, insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility criteria were identified. The second study comprised a survey among self-reported insomnia patients. It was determined to what extent RCT eligibility criteria match the characteristics of this patient population. Of the n = 519 patients that completed the survey only n = 2 (0.4%) met all eligibility criteria of current RCTs. RCT enrolment criteria are not representative for the insomnia patient population as a whole. Being less rigorous in applying upper or lower criteria limits results in a significant increase in the number of eligible patients, and increases the representativeness of RCTs for the insomnia patient population as a whole. The current analysis demonstrates that is important to thoroughly reconsider the use eligibility criteria and their inclusion ranges, and to have a theoretical basis for using them.

Susceptibility to Alcohol Hangovers: The Association with Self-Reported Immune Status.

Increasing evidence points at a role for the immune system in the genesis of the alcohol hangover. This study investigated the association between self-reported immune function and experiencing hangovers. Dutch students aged 18 to 30 years old were invited to complete an online survey. Eighteen items on immune-related complaints were completed to assess self-reported immune function. Alcohol consumption in the past month (with respect to usual consumption and the occasion of heaviest drinking) was also recorded. Subjects with an estimated blood alcohol concentration (eBAC) of 0.18% or higher on their heaviest drinking occasion in the prior month were included in the analyses. Self-reported immune function was compared between drinkers with a hangover and those who claimed to be hangover resistant. In total, of 481 subjects (79.2% women) with a mean (SD) age of 21.1 (1.9) years old were included in the analysis. Of these, 83.3% (n = 400) reported having hangovers and 16.8% (n = 81) claimed to be hangover resistant. Drinkers with hangovers had significantly higher self-reported overall immune function scores when compared to hangover-resistant drinkers (mean ± SD = 10.5 ± 3.6 versus 13.1 ± 4.9, p = 0.0001), indicating a poorer immune status. In conclusion, experiencing alcohol hangovers is associated with significantly poorer self-reported immune function.

Differences in the Temporal Typology of Alcohol Hangover.

BACKGROUND: At a group level, hangover severity during the day has been described to follow an inverted U-shaped curve, with gradually increasing severity scores that, after reaching a peak, gradually decrease toward zero. The aim of this study was to examine if and how individual drinkers' hangover severity scores vary during the day. METHODS: Data from a survey (Penning et al., ) in which 727 drinkers reported on their latest alcohol hangover were reanalyzed. The temporal pattern of each individual's hangover was first categorized as belonging to 1 of 6 types based on predefined temporal characteristics. RESULTS: Three dominant hangover patterns emerged as comprising more than 95% of the sample: (i) a continuous decline hangover (Severity Type 1 hangover, 54.5%), (ii) a steady state hangover (Severity Type 2 hangover, 19.1%), and (iii) an inverted U-shaped curve hangover (Severity Type 3 hangover, 21.8%). Of these 3 patterns, Severity Type 2 hangovers are associated with significantly less alcohol consumption and with having the lowest severity scores of individual hangover symptoms. Severity Type 1 hangovers are associated with having the highest severity of individual hangover symptoms. In line with significantly lower levels of alcohol consumption, Severity Type 2 hangovers were significantly more often observed in women when compared to men. Severity Type 1 hangovers were significantly more common in men than in women. Severity Type 3 hangovers, characterized by the increased presence of gastrointestinal complaints, were equally commonly experienced in men and women. CONCLUSIONS: This study revealed that the temporal pattern of hangover severity can follow marked interindividual variability. Three common temporal patterns were identified, which are uniquely related to the amount of alcohol consumed and the presence and severity of different individual hangover symptoms. Better understanding of individual differences in hangover typology may help to delineate mechanisms underlying alcohol hangover.

Susceptibility to Alcohol Hangovers: Not Just a Matter of Being Resilient.

INTRODUCTION: Although most drinkers have experienced a hangover the day following heavy alcohol consumption, a minority claims to be hangover resistant despite consuming the same large quantities of alcohol as those reporting alcohol hangover. The aim of the current study was to examine if susceptibility to experiencing hangovers is related to a drinker's interpretation of wellbeing and psychological assets to bounce back. METHODS: A survey was conducted among 2295 Dutch students assessing their past month alcohol consumption patterns, and measuring mental resilience and wellbeing. Estimated peak blood alcohol concentration (e-pBAC) for their heaviest drinking occasion in the past month was computed for each participant. Data from participants who reported a past month hangover, i.e. hangover sensitive drinkers, were compared with hangover resistant drinkers. The analyses were conducted for (a) all participants reaching an e-pBAC ≥ 0.11% (N = 986, of which 24.6% claimed to be hangover resistant) and (b) participants reaching an e-pBAC ≥ 0.18% (N = 480, of which 16.7% claimed to be hangover resistant). RESULTS: For both e-pBAC cut-off values, no significant differences between hangover sensitive and hangover resistant drinkers were found for mental resilience and wellbeing. CONCLUSION: The current findings suggest that having a hangover is not simply an expression of poor psychological coping with the next-day consequences of heavy alcohol consumption.

The impact of alcohol hangover symptoms on cognitive and physical functioning, and mood.

Hangover research often records the presence and severity of symptoms experienced the day after heavy alcohol consumption. However, usually no information is gathered on the impact of experiencing these symptoms on mood, cognition, and physical activities. An online survey was held among Dutch students, aged 18-30 years, who recently had a hangover. Overall hangover severity (i.e., a single 1-item rating) and the severity of 22 individual symptoms were rated on an 11-point scale ranging from 0 (absent) to 10 (extreme). In addition, for each symptom, participants were asked to rate their respective negative impact on (a) cognitive functioning, (b) physical functioning, and (c) mood, on a 6-point Likert scale ranging from 0 (no impact) to 5 (extreme). N = 1837 subjects completed the survey. The mean (SD) overall (1-item) hangover severity score was 6.1 (1.9). Sleepiness, being tired, thirst, and concentration problems were the most frequently reported hangover symptoms. These symptoms also reached the highest severity scores (ranging from 6.3 to 7.0). The 4 symptoms with the biggest combined impact on mood, and cognitive and physical functioning were being tired, sleepiness, headache, and concentration problems. In conclusion, whereas severity and impact scores usually correspond well, some frequently reported symptoms with moderate to high severity scores had little impact on mood, and cognitive and physical functioning (i.e., reduced appetite, regret, and thirst).

The effects of intranasal esketamine (84 mg) and oral mirtazapine (30 mg) on on-road driving performance: a double-blind, placebo-controlled study.

RATIONALE: The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance. METHODS: Twenty-six healthy volunteers aged 21 to 60 years were enrolled in this study. In the evening, 8 h after treatment administration, participants conducted the standardized 100-km on-road driving test. Primary outcome measure was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Mean lateral position, mean speed, and standard deviation of speed were secondary outcome measures. For SDLP, non-inferiority analyses were conducted, using +2.4 cm (relative to placebo) as a predefined non-inferiority margin for clinical relevant impairment. RESULTS: Twenty-four participants completed the study. No significant SDLP difference was found between esketamine and placebo (p = 0.7638), whereas the SDLP after mirtazapine was significantly higher when compared to placebo (p = 0.0001). The upper limit of the two-sided 95% confidence interval (CI) of the mean difference between esketamine and placebo was +0.86 cm, i.e., <+2.4 cm, thus demonstrating that esketamine was non-inferior to placebo. Non-inferiority could not be concluded for mirtazapine (+3.15 cm SDLP relative to placebo). No significant differences in mean speed, standard deviation of speed, and mean lateral position were observed between the active treatments and placebo. CONCLUSIONS: No significant difference in driving performance was observed 8 h after administering intranasal esketamine (84 mg) or placebo. In contrast, oral mirtazapine (30 mg) significantly impaired on road driving performance.