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BACKGROUND: The traditional outcome measure of the Dutch on-the-road driving test is the standard deviation of lateral position (SDLP), the weaving of the car. This paper explores whether excursions out-of-lane are a suitable additional outcome measure to index driving impairment. METHODS: A literature search was conducted to search for driving tests that used both SDLP and excursions out-of-lane as outcome measures. The analyses were limited to studies examining hypnotic drugs because several of these drugs have been shown to produce next-morning sedation. RESULTS: Standard deviation of lateral position was more sensitive in demonstrating driving impairment. In fact, solely relying on excursions out-of-lane as outcome measure incorrectly classifies approximately half of impaired drives as unimpaired. The frequency of excursions out-of-lane is determined by the mean lateral position within the right traffic lane. Defining driving impairment as having a ΔSDLP > 2.4 cm, half of the impaired driving tests (51.2%, 43/84) failed to produce excursions out-of-lane. Alternatively, 20.9% of driving tests with ΔSDLP CONCLUSIONS: Excursions out-of-lane are neither a suitable measure to demonstrate driving impairment nor is this measure sufficiently sensitive to differentiate adequately between differences in magnitude of driving impairment. Copyright © 2014 John Wiley & Sons, Ltd. Language: en

Hangover is the most commonly reported negative consequence of heavy alcohol consumption. A large variety of symptoms have been reported the day after heavy drinking, which together are called the alcohol hangover. Frequently reported hangover symptoms include thirst, headache, drowsiness, and reduced alertness [1]. Although hangover is a common phenomenon in society and has serious socioeconomic consequences, it has received relatively little research attention. To increase research and international collaboration to examine the alcohol hangover, in 2010 the Alcohol Hangover Research Group (AHRG) was founded. This paper covers the research topics discussed at the 5th Alcohol Hangover Research Group meeting, held August 1–2, 2013 in Keele, UK.

BACKGROUND: The on-the-road driving test in normal traffic is used to examine the impact of drugs on driving performance. This paper compares the sensitivity of standard deviation of lateral position (SDLP) and SD speed in detecting driving impairment. METHODS: A literature search was conducted to identify studies applying the on-the-road driving test, examining the effects of anxiolytics, antidepressants, antihistamines, and hypnotics. The proportion of comparisons (treatment versus placebo) where a significant impairment was detected with SDLP and SD speed was compared. RESULTS: About 40% of 53 relevant papers did not report data on SD speed and/or SDLP. After placebo administration, the correlation between SDLP and SD speed was significant but did not explain much variance (r = 0.253, p = 0.0001). A significant correlation was found between ΔSDLP and ΔSD speed (treatment-placebo), explaining 48% of variance. When using SDLP as outcome measure, 67 significant treatment-placebo comparisons were found. Only 17 (25.4%) were significant when SD speed was used as outcome measure. Alternatively, for five treatment-placebo comparisons, a significant difference was found for SD speed but not for SDLP. CONCLUSIONS: Standard deviation of lateral position is a more sensitive outcome measure to detect driving impairment than speed variability. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

Even though there are indications that stress influences body temperature in humans, no study has systematically investigated the effects of stress on core and peripheral body temperature. The present study therefore aimed to investigate the effects of acute psychosocial stress on body temperature using different readout measurements. In two independent studies, male and female participants were exposed to a standardized laboratory stress task (the Trier Social Stress Test, TSST) or a non-stressful control task. Core temperature (intestinal and temporal artery) and peripheral temperature (facial and body skin temperature) were measured. Compared to the control condition, stress exposure decreased intestinal temperature but did not affect temporal artery temperature. Stress exposure resulted in changes in skin temperature that followed a gradient-like pattern, with decreases at distal skin locations such as the fingertip and finger base and unchanged skin temperature at proximal regions such as the infra-clavicular area. Stress-induced effects on facial temperature displayed a sex-specific pattern, with decreased nasal skin temperature in females and increased cheek temperature in males. In conclusion, the amplitude and direction of stress-induced temperature changes depend on the site of temperature measurement in humans. This precludes a direct translation of the preclinical stress-induced hyperthermia paradigm, in which core temperature uniformly rises in response to stress to the human situation. Nevertheless, the effects of stress result in consistent temperature changes. Therefore, the present study supports the inclusion of body temperature as a physiological readout parameter of stress in future studies.

Time dependent decrements in performance are characteristic of activities that are monotonous and require focused attention for an extended period of time. A vigilance task is a task that participants can perform without difficulty for a short period of time, but with time their performance becomes impaired. A real world example of such a vigilance task is prolonged highway driving. The on-the-road driving test in normal traffic was specifically designed to measure the effects of vigilance decrement associated with driving. The primary parameter of this test is the Standard Deviation of Lateral Position (SDLP), i.e. the weaving of the car. This methodological paper explains the typical vigilance decrement seen in the on-the-road driving test and discusses the importance of sufficient time-on-task to elucidate potential adverse drug effects on driving. Performance decrements (SDLP increment) as a function of time are seen after both drug and placebo treatment, following a similar pattern over distance/time traveled. However, whereas for some drugs SDLP differences between drug and placebo are constant, other drugs produce additional performance decrement that increases over distance traveled. It is concluded that driving tests of short duration (e.g. less than half an hour) may fail to detect drug-related impairment, because participants are capable of, at least in part, counteracting the impairment by increased effort and motivation to perform the test.

Decisions are rarely made in social isolation. One phenomenon often observed in social interactions is altruistic punishment, i.e. the punishment of unfair behavior by others at a personal cost. The tendency for altruistic punishment is altered by affective states including those induced by stress exposure. Stress is thought to exert bi-directional effects on behavior: immediately after stress, reflex-like and habitual behavior is promoted while later on more far-sighted, flexible and goal-directed behavior is enhanced. We hypothesized that such time-dependent effects of stress would also be present in the context of altruistic punishment behavior. Healthy male participants (N=80) were exposed to either a grouped stress test or a control condition. Participants were tested in prosocial decision making tasks either directly after stress or 75 min later. Altruistic punishment was assessed using the Ultimatum Game. General altruism was assessed with a one-shot version of the Dictator Game in which an anonymous donation could be offered to a charitable organization. We found that stress caused a bi-directional effect on altruistic punishment, with decreased rejection rates in the late aftermath of stress in response to ambiguous 30% offers. In the Dictator Game, stressed participants were less generous than controls, but no time-dependent effect was observed, indicating that the general reward sensitivity remained unchanged at various time-points after stress. Overall, during the late aftermath after acute stress exposure (i.e. 75 min later), participants acted more consistent with their own material self-interest, and had a lower propensity for altruistic punishment, possibly through upregulation of cognitive self-control mechanisms. Thus, our findings underscore the importance of time as a factor in simple, real-life economic decisions in a stressful social context.

OBJECTIVES: The aim of this study was to examine the next day effects of alcohol consumption on a range of attention tasks. METHODS: The study followed a counterbalanced repeated measure design, with participants tested the morning following normal/usual alcohol consumption and again the morning after no alcohol consumption. Participants were 48 social drinkers (15 men and 33 women), who performed attention tests at 9 am, 11 am, or 1 pm. Performance was assessed by tasks measuring sustained attention, divided attention, selective attention, and spatial attention and by the Stroop test. RESULTS: The morning after alcohol consumption, a significantly higher proportion of missed targets was observed (F(1, 40) = 6.43, p Language: en

Lydia de Haan,1 Hein A de Haan,2,3 Berend Olivier,1 Joris C Verster11Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacology, Utrecht, The Netherlands; 2Tactus Addiction Treatment, Deventer, The Netherlands; 3Nijmegen Institute for Scientist-Practitioners in Addiction, Nijmegen, The NetherlandsAbstract: This paper describes the methodology of the Utrecht Student Survey. This online survey was conducted in June 2011 by 6002 students living in Utrecht, The Netherlands. The aim of the survey was to determine the potential impact of mixing alcoholic beverages with energy drinks on overall alcohol consumption and alcohol-related consequences. In contrast to most previous surveys conducted on this topic, the current survey used a more appropriate within-subject design, comparing the alcohol consumption of individuals who consume alcohol mixed with energy drinks on occasions. Specifically, a comparison was conducted to examine the occasions during which these individuals consume this mixture versus occasions during which they consume alcohol alone. In addition to energy drinks, the consumption of other non-alcoholic mixers was also assessed when combined with alcoholic beverages. Furthermore, the reasons for consuming energy drinks alone or in combination with alcohol were investigated, and were compared to reasons for mixing alcohol with other non-alcoholic beverages. Finally, personality characteristics and the level of risk-taking behavior among the individuals were also assessed to explore their relationship with alcohol consumption. The Utrecht Student Survey will be replicated in the USA, Australia, and the UK. Results will be pooled, but also examined for possible cross-cultural differences.Keywords: energy drink, alcohol, alcohol related consequences, survey, methodology

Objective The aimof this study was to compare performance measures after acute alcohol consumption (intoxication) with the performance the day after a normal nightâ?Ts drinking (hangover). Methods Eighty-four social drinkers took part in two studies that followed a counterbalanced repeated measure design. Fifteen men and 33 women were tested the morning (09:00, 11:00 or 13:00 h) following normal/usual alcohol consumption and the morning after no alcohol consumption; the order of testing was counterbalanced. In a second study, 36 participants (18 men and 18 women) were tested after receiving alcohol to attain a blood alcohol concentration of 0.08%, and after no alcohol administration, the order of testing was counterbalanced. In both studies, participants completed a task battery of memory, reaction time and attention tasks. Results Alcohol had no effect on the free recall task and the spatial attention task. Alcohol consumption, either acute or the next day, significantly affected reaction time, divided attention, selective attention and Stroop interference. The impairments during intoxication and hangover were of comparable magnitude. Performance on tasks of delayed recognition and irregular interstimulus reaction time was worse during hangover when compared with intoxication. Conclusion It is evident that awareness needs to be raised that performance the morning after alcohol consumption is at the same level if not worse than when participants are at the legal limit for driving (0.08% blood alcohol concentration).

Rationale This study investigated the coadministration of an energy drink with alcohol to study the effects on subjective intoxication and objective performance. Objectives This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design. Methods Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5), participated in the study. One group consumed energy drink containing 80 mg of caffeine and the other consumed a placebo drink, with both receiving two alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word memory and Stroop task) and subjective visual analogue mood scales. Results Participants showed significantly impaired reaction time and memory after alcohol compared to the no alcohol condition and had poorer memory after the higher alcohol dose. Stroop performance was improved with the energy drink plus alcohol combination compared to the placebo drink plus alcohol combination. Participants felt significant subjective dose-related impairment after alcohol compared to no alcohol. Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol. Conclusions Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose. There were no overall significant group differences for subjective measures between energy drink and placebo groups in the presence of alcohol and no evidence that the energy drink masked the subjective effects of alcohol at either dose.

Scientific literature suggests a large number of symptoms that may be present the day after excessive alcohol consumption. The purpose of this study was to explore the presence and severity of hangover symptoms, and determine their interrelationship.A survey was conducted among n = 1410 Dutch students examining their drinking behavior and latest alcohol hangover. The severity of 47 presumed hangover symptoms were scored on a 10-point scale ranging from 0 (absent) to 10 (maximal). Factor analysis was conducted to summarize the data into groups of associated symptoms that contribute significantly to the alcohol hangover and symptoms that do not.About half of the participants (56.1%, n = 791) reported having had a hangover during the past month. Most commonly reported and most severe hangover symptoms were fatigue (95.5%) and thirst (89.1%). Factor analysis revealed 11 factors that together account for 62% of variance. The most prominent factor 'drowsiness' (explained variance 28.8%) included symptoms such as drowsiness, fatigue, sleepiness and weakness. The second factor 'cognitive problems' (explained variance 5.9%) included symptoms such as reduced alertness, memory and concentration problems. Other factors, including the factor 'disturbed water balance' comprising frequently reported symptoms such as 'dry mouth' and 'thirst', contributed much less to the overall hangover (explained variance5%).Drowsiness and impaired cognitive functioning are the two dominant features of alcohol hangover.

Introduction and objectives The on-the-road driving test in normal traffic is applied to examine the impact of drugs on driving performance. Although participants are accompanied by a licensed driving instructor, under Dutch law, the driver is primarily responsible for safe driving and is not permitted to continue driving when it is judged that the drug compromises safety. This review examined the prevalence and nature of stopped driving tests, and the relationship with Standard Deviation of Lateral Position (SDLP), i.e. the “weaving of the car”. Materials and methods A literature search was conducted to gather all publications on clinical trials that applied the on-the-road driving test, examining the effects of Central Nervous System (CNS)-drugs such as anxiolytics, antidepressants, antihistamines, analgesics, and hypnotics. Results 47 papers reported on 50 Dutch clinical trials in which 1059 subjects participated (903 healthy volunteers and 156 patients). A total of 7232 driving tests were performed; 5050 after drug treatment and 2042 after placebo. 3.1% of all driving tests were terminated before completion: 4.1% after drug treatment, and 0.7% after placebo. The decision to stop a driving test was 3–4 times more often made by the driving instructor than the subject. The most common reasons for stopping were the driver feeling tired or sleepy, or the driving instructor noticing signs of drowsiness and performance impairment. Although SDLP values of stopped driving tests are sometimes high, there is no clear relationship between SDLP (changes from placebo) and the decision to stop a driving test. Based on 8 studies that reported exact data, 39.6% of stopped drivers had a lower and 60.4% had a higher SDLP than 35 cm, i.e. the cut-off point of safe driving. This confirms that perception of the driver as well as judgment by the instructor of driving to be ‘unsafe’ differs between individuals. Conclusion Driving tests are sometimes stopped after drug treatment or placebo. The decision to stop driving is not a good correlate of objective performance.

Rationale Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. Objectives The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. Methods Non-sleep deprived healthy volunteers (n = 24) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. Results The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p = 0.024) and second hour (p = 0.019) after the break. Similarly, the standard deviation of speed (p = 0.024; p = 0.001), mental effort (p = 0.003; p = 0.023), and subjective sleepiness (p = 0.001; p = 0.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p = 0.004). Conclusions These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving.

In industrialized countries one-fifth of all traffic accidents can be ascribed to sleepiness behind the wheel. Driver sleepiness can have many causes, including the use of medicinal drugs or prolonged driving. The present study compared the effects of prolonged highway driving at night with driving impairment caused by alcohol. A cross-over balanced design tested 14 healthy young men who drove three sessions during night-time on the open road. The driving sessions were of 2, 4 and 8 h (03:00-05:00, 01:00-05:00 and 21:00-05:00 hours) duration. Standard deviation of lateral position (SDLP, cm), measuring the weaving of the car in the last driving hour of each session, was the primary parameter. Only 2 h of continuous nocturnal driving were sufficient to produce driving impairment comparable to a blood alcohol concentration (BAC) of 0.05%; after 3 h of driving impairment corresponds to a BAC of 0.08%. In conclusion, a maximum of two continuous nocturnal driving hours should be recommended.

The search for alcohol hangover cures is as old as alcohol itself. Many cures and prophylactic agents are available, but scientific evidence for their effectiveness is generally lacking. This review summarizes and discusses the limited number of studies that examined the effectiveness of alcohol hangover treatments. From these studies it must be concluded that most remedies do not significantly reduce overall hangover severity. Some compounds reduce specific symptoms such as vomiting and headache, but are not effective in reducing other common hangover symptoms such as drowsiness and fatigue. Hangover cures that showed positive effects were those inhibiting prostaglandin synthesis or accelerating alcohol metabolism. Future studies should elucidate the pathology of alcohol hangover. Until then, it is unlikely that an effective hangover cure will be developed. Language: en

Objectives: The literature exploring the role that cytokine functioning plays in the pathogenesis and treatment of depressive illness is reviewed. The review focuses on the influence of antidepressants on cytokines, and on how treatment response might be affected by genetic variants of cytokines. Method: The authors systematically reviewed the scientific literature on the subject over the last 20 years, searching PubMed, PsychInfo, and Cochrane databases. Results: Antidepressants modulate cytokine functioning, and these mechanisms appear to directly influence treatment outcome in depression. Antidepressants appear to normalize serum levels of major inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ). Antidepressants are postulated to modulate cytokine functioning through their effects on intracellular cyclic adenosyl monophosphate (cAMP), serotonin metabolism, the hypothalamo-pituitary-adrenocortical (HPA) axis or through a direct action on neurogenesis. Preliminary research shows that cytokine genotypes and functioning may be able to help predict antidepressant treatment response. Conclusions: Current literature demonstrates an association between antidepressant action and cytokine functioning in major depression. Improved understanding of the specific pharmacologic and pharmacogenetic mechanisms is needed. Such knowledge may serve to enhance our understanding of depression, leading to promising new directions in the pathology, nosology, and treatment of depression.

Contains fulltext : 87790.pdf (Publisher’s version ) (Closed access) BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory functioning of adults with ADHD. METHODS: Eighteen adults with ADHD who were clinical responders to methylphenidate participated in this randomized crossover trial. After 3 days of no treatment, patients received in random order either their usual methylphenidate dose (mean: 14.7 mg; range: 10-30 mg) or placebo, separated by a 6-7-day washout period. Patients performed an immediate word recall test 1 h after treatment administration. Three hours after intake, patients performed the second part of the memory test (delayed word recall and a recognition test). RESULTS: Delayed recognition and immediate recall was similar on treatment and on placebo. Delayed word recall was significantly better in the methylphenidate than in the placebo condition (F (1, 17) = 7.0, p < 0.017). A significant correlation was found between prestudy CES-D depression scores and difference scores on delayed recall (r = 0.602, p < 0.008). CONCLUSION: Methylphenidate improves declarative memory functioning in patients with ADHD. New studies should further examine whether subclinical depressive symptoms mediate the effect of methylphenidate on declarative memory. 01 oktober 2010

The purpose of this study was to validate the Dutch version of the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ).The B-YAACQ was translated into the Dutch language and 800 students were invited to complete the questionnaire. A number of drinking behaviors were also assessed; including weekly drinking, age of drinking onset, and blood alcohol concentration on a typical night out. Students also completed a short version of the Alcohol Use Disorders Identification Test (AUDIT-PC).Data from 667 undergraduate and graduate students (184 men and 483 women) who reported alcohol use during the past year was used in the analysis. On average, students in this study report 4.7 alcohol-related consequences. The Dutch B-YAACQ was shown to have a high reliability and validity: Cronbach's Alpha was 0.816, and B-YAACQ scores correlated significantly with AUDIT-PC scores (r=0.747). B-YAACQ scores correlated significantly (p0.01) with various drinking variables, including drinking onset age, drinking days per week, alcoholic drinks per week, number of drinks on a night out and blood alcohol concentration when returning home.The Dutch B-YAACQ is a useful new tool for screening of alcohol-related consequences.

Driving a car is important to maintain independence and participate in society. Many of those who use psychoactive medication are outpatients and are thus likely to drive a vehicle. Most common adverse effects that impair driving are reduced alertness, affected psychomotor functioning and impaired vision. This review discusses the effects on driving ability of most commonly prescribed psychoactive drugs, including hypnotics, antidepressants, antihistamines, analgesics and stimulant drugs. Within these categories of medicines significant differences concerning their impact on driving ability are evident. The International Council on Alcohol, Drugs and Traffic Safety (ICADTS) categorization can help physicians to make a choice between treatments when patients want to drive a car.

Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.

Zolpidem is among the most frequently prescribed hypnotic drugs for those who suffer from insomnia. Recent media reports drew attention to driving impairment after zolpidem misuse. This review summarizes the available data on the effects of recommended use and misuse of zolpidem on driving ability and traffic safety. Both experimental studies and roadside evidence were taken into account. From these studies it must be concluded that patients should fully comply with the prescription instructions of zolpidem, i.e. to take the medication just prior to a full 8 hours of uninterrupted sleep. If this strategy is adopted, zolpidem is a safe alternative to benzodiazpine hypnotics and zopiclone who do show significant driving impairment the morning following bedtime administration. However, to ensure traffic safety higher dosages than recommended (10 mg) or allowing less than 8 hours between zolpidem intake and actual operation of a motor vehicle should be avoided.

Sleep disorders are not uncommon and have been widely reported throughout the world. They have a profound impact on industrialized 24-h societies. Consequences of these problems include impaired social and recreational activities, increased human errors, loss of productivity, and elevated risk of accidents. Conditions such as acute and chronic insomnia, sleep loss, excessive sleepiness, shift-work, jet lag, narcolepsy, and sleep apnea warrant public health attention, since residual sleepiness during the day may affect performance of daily activities such as driving a car. Benzodiazepine hypnotics and zopiclone promote sleep, both having residual effects the following day including sleepiness and reduced alertness. In contrast, the non-benzodiazepine hypnotics zolpidem and zaleplon have no significant next-day residual effects when taken as recommended. Research on the effects of wakefulness-promoting drugs on driving ability is limited. Countermeasures for excessive daytime sleepiness have a limited effect. There is a need for a social awareness program to educate the public about the potential consequences of various sleep disorders such as narcolepsy, sleep apnea, shift-work-related sleep loss, and excessive daytime sleepiness in order to reduce the number of sleep-related traffic accidents. Mount Sinai School of Medicine Division of Pulmonary, Critical Care, and Sleep Medicine University of Utrecht Utrecht Institute for Pharmaceutical Sciences Department of Psychopharmacology University of Toronto, and Sleep and Neuropsychiatry Institute Department of Psychiatry Universidade Federal de São Paulo (UNIFESP) Departamento de Psicobiologia UNIFESP, Depto. de Psicobiologia SciELO

Most pain patients are treated in an outpatient setting and are engaged in daily activities including driving. Since several studies showed that cognitive functioning may be impaired in chronic nonmalignant pain, the question arises whether or not chronic nonmalignant pain affects driving performance. Therefore, the objective of the present study was to determine the effects of chronic nonmalignant pain on actual highway driving performance during normal traffic. Fourteen patients with chronic nonmalignant pain and 14 healthy controls, matched on age, educational level, and driving experience, participated in the study. Participants performed a standardized on-the-road driving test during normal traffic, on a primary highway. The primary parameter of the driving test is the Standard Deviation of Lateral Position (SDLP). In addition, driving-related skills (tracking, divided attention, and memory) were examined in the laboratory. Subjective assessments, such as pain intensity, and subjective driving quality, were rated on visual analogue scales. The results demonstrated that a subset of chronic nonmalignant pain patients had SDLPs that were higher than the matched healthy controls, indicating worse highway driving performance. Overall, there was a statistically significant difference in highway driving performance between the groups. Further, chronic nonmalignant pain patients rated their subjective driving quality to be normal, although their ratings were significantly lower than those of the healthy controls. No significant effects were found on the laboratory tests.

Most patients using hypnotics are ambulatory and presumably have a job and drive a car. Since driving a car is one of the most common but potentially dangerous daily activities, hypnotics should act rapidly when needed, but daytime sleepiness and other residual effects that may impair performance are unwanted. This review summarizes the effects of hypnotics on driving ability as determined with the on-the-road driving test during normal traffic. Supportive evidence from epidemiological data, and results from driving simulators and closed-road studies are also considered. On-the-road studies revealed that benzodiazepine hypnotics significantly impaired driving ability the morning following bedtime administration. Impairment was sometimes also significant in the afternoon (16-17 h after administration). Similar driving impairment was observed with zopiclone. However, the magnitude of impairment depends on various factors including the half-life and dosage of the drug, and the time after administration. The results from on-the-road driving studies are supported by evidence obtained in driving simulators and laboratory tests. Epidemiological data and on-the-road studies show that tolerance develops to the impairing effects of hypnotics. However, this is a slow process, and impairment may persist. Patients treated with benzodiazepine hypnotics or zopiclone should be cautioned when driving a car. Both zolpidem and zaleplon do not significantly affect driving performance the morning following bedtime administration. Middle-of-the-night administration of zolpidem significantly impairs driving ability in a dose-dependent manner. In contrast, zaleplon did not affect driving ability 4 h after middle-of-the-night administration.

Sedation following antihistamine use poses a danger to ambulant patients involved in daily activities such as driving. To investigate effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on driving ability during normal traffic. Forty-eight healthy volunteers participated in a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3 and 4, exactly 1.5 h before the start of the standardized driving test (performed on day 1 and day 4). In the standardized driving test, subjects were instructed to drive with a steady lateral position, while maintaining a constant speed (95 km/h). Primary parameter was the standard deviation of lateral position (SDLP; cm). Statistical analyses were performed separately for day 1 and day 4, using analysis of variance and an equivalence test. Equivalence to placebo was evidenced if the 95% confidence interval lay between −2.6 cm and +2.6 cm. SDLP after levocetirizine was equivalent to placebo on both day 1 (−0.66 cm; +1.12 cm) and day 4 (−0.37 cm; +1.28 cm). In contrast, SDLP after diphenhydramine differed significantly from placebo on both day 1 (P

Central nervous system adverse effects, such as sedation, often accompany the use of first-generation antihistamines. These effects might interfere with memory functioning and psychomotor performance. Levocetirizine was recently introduced as a new antihistamine said to be free from sedative effects.We sought to investigate the effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on memory and psychomotor performance after acute (day 1) and subchronic (day 4) daily administration in 48 healthy volunteers (24 men and 24 women).This study was a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3, and 4, 3 hours before the start of the laboratory test battery (performed on days 1 and 4), comprising a word-learning test, the Sternberg Memory Scanning Test, a tracking test (easy and hard version), and a divided attention test (tracking and memory scanning simultaneously). Statistical analyses were performed separately for days 1 and 4 by using analysis of variance.On day 1, diphenhydramine significantly impaired tracking performance (easy: F(1,90) = 25.9, P.0001; hard: F(1,90) = 20.5, P.0001) and divided attention (tracking: F(1,90) = 23.8, P.0001; memory scanning: F(1,90) = 22.0, P.0001). Results on word-learning tests and Sternberg Memory Scanning Tests were not significantly impaired. On day 4, the effects of diphenhydramine did not reach significance. In contrast, on both days 1 and 4, levocetirizine did not significantly impair laboratory test performance.The results show that memory, attention, and tracking performance are unaffected after acute and subchronic administration of levocetirizine (5 mg), whereas diphenhydramine (50 mg) significantly affected divided attention and tracking after acute administration.

Thirty healthy volunteers participated in this two-part study. Part 1 was a single-blind, two-period crossover design to determine the effects of a single dose of ethanol (0.03% < BAC < 0.05%) or ethanol-placebo on driving ability, memory, and psychomotor performance. Part 2 was a double-blind, five-period crossover design to measure the effects of a middle-of-the-night administration of zaleplon 10 or 20 mg, zolpidem 10 or 20 mg, or placebo on driving ability 4 hours after administration and memory and psychomotor performance 6 hours after administration. The on-the-road driving test consisted of operating an instrumented automobile over a 100-km highway circuit at a constant speed (95 km/h) while maintaining a steady lateral position between the right lane boundaries. The standard deviation of lateral position (SDLP) was the primary performance parameter of the driving test. The psychomotor and memory test battery consisted of the Word Learning Test, the Critical Tracking Test, the Divided Attention Test, and the Digit Symbol Substitution Test. Data for each part were analyzed separately using ANOVA for crossover designs. Zaleplon 10 and 20 mg did not significantly impair driving ability 4 hours after middle-of-the-night administration. Relative to placebo, after zolpidem 10 mg, SDLP was significantly elevated, but the magnitude of the difference was small and not likely to be of clinical importance. Memory and psychomotor test performance was unaffected after both doses of zaleplon and zolpidem 10 mg. In contrast, zolpidem 20 mg significantly increased SDLP and speed variability. Further, zolpidem 20 mg significantly impaired performance on all psychomotor and memory tests. Finally, driving performance, Digit Symbol Substitution Test, Divided Attention Test, and immediate and delayed free recall of the Word Learning Test were significantly impaired after ethanol. The results show that zaleplon (10 and 20 mg) is a safe hypnotic devoid of next-morning residual impairment when used in the middle of the night.

The impairing effects on memory functioning after acute alcohol intoxication in healthy volunteers and after chronic use in alcoholics are well established. However, research determining the next-morning effects of a single episode of binge drinking on memory functioning is scarce. A total of 48 healthy volunteers participated in a single-blind study comprising an evening (baseline) session, followed by a treatment administration (ethanol 1.4 g/kg or placebo), and a morning session. Memory was tested with a word-learning test (including immediate and delayed recall, and recognition). Further, a 45-min Mackworth clock test for measuring vigilance was included (parameters: number of hits and false alarms) and subjective alertness was assessed, to infer whether word-learning test findings reflect sedation or specific memory impairments. Delayed recall in the morning session was significantly worse in the alcohol group when compared to the placebo group (F(1,42)=6.0, p

Study objectives. Sleep maintenance problems are common, hence treatments enabling patients to fall asleep more rapidly after middle-of-the-night (MOTN) awakenings, without impairing next morning alertness, are needed. This literature review compares the effects of MOTN administration of various hypnotics on morning driving ability, a potentially dangerous daily activity under conditions of impairment. METHODS. A literature search was conducted identifying on-the-road driving studies examining the effects of MOTN administration of hypnotics on morning driving performance. In a standardized 100-km highway driving test in normal traffic, subjects were instructed to drive with a steady lateral position and constant speed of 95 km/h. The primary outcome measure of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), i.e. weaving of the car. RESULTS. Four driving studies were identified. Driving performance after MOTN administration of traditional benzodiazepine hypnotics was not examined. Zolpidem (10 mg and 20 mg, oral immediate release tablets) significantly impaired driving in a dose-dependent manner, when tested 4 hours after MOTN administration. Also, gaboxadol (15 mg) and zopiclone (7.5 mg) significantly impaired next-morning driving after MOTN administration. In contrast, sublingual zolpidem (3.5 mg) and zaleplon (10 mg and 20 mg) did not significantly affect driving 4 hours after MOTN administration. CONCLUSIONS. Driving was not affected 4 hours after MOTN administration of sublingual zolpidem (3.5 mg) or zaleplon (10 mg and 20 mg). Significant driving impairment was found after MOTN administration of zolpidem (10 and 20 mg), gaboxadol (15 mg), and zopiclone (7.5 mg). Language: en

Recent laboratory studies have shown that men display more risk-taking behavior in decision-making tasks following stress, whilst women are more risk-aversive or become more task-focused. In addition, these studies have shown that sex differences are related to levels of the stress hormone cortisol (indicative of activation of the hypothalamus-pituitary-adrenocortical-axis): the higher the levels of cortisol the more risk-taking behavior is shown by men, whereas women generally display more risk-aversive or task-focused behavior following higher levels of cortisol. Here, we assessed whether such relationships hold outside the laboratory, correlating levels of cortisol obtained during a job-related assessment procedure with decision-making parameters in the Cambridge Gambling Task (CGT) in male and female police recruits. The CGT allows for discriminating different aspects of reward-based decision-making. In addition, we correlated levels of alpha-amylase [indicative of activation of the sympatho-adrenomedullary-axis (SAM)] and decision-making parameters. In line with earlier studies men and women only differed in risk-adjustment in the CGT. Salivary cortisol levels correlated positively and strongly with risk-taking measures in men, which was significantly different from the weak negative correlation in women. In contrast, and less strongly so, salivary alpha-amylase levels correlated positively with risk-taking in women, which was significantly different from the weak negative correlation with risk-taking in men. Collectively, these data support and extend data of earlier studies indicating that risky decision-making in men and women is differently affected by stress hormones. The data are briefly discussed in relation to the effects of stress on gambling.

Attention-Deficit Disorder with Hyperactivity (ADHD) has the core symptoms of inattention, impulsivity, and hyperactivity and is among the most prevalent disorders in childhood, affecting about 3-10% of U.S. school-aged children. In adults, the prevalence of ADHD is about 4%, present equally in men and women. With maturation, hyperactive symptoms often diminish in patients with ADHD; however, attention deficits and impulsivity often persist and can have a significant impact on functioning. Although the symptoms of inattention and impulsivity of those with ADHD apparently impair driving performance, use of methylphenidate appears to improve, and possibly normalize, the driving performance of those with ADHD. This issue features the results of the first naturalistic driving study performed on a 100-km public highway circuit during normal traffic examining driving ability of patients with ADHD after treatment with methylphenidate or placebo. The authors used objective measurements of driving performance including the weaving of the car and speed variability, whereas patients were instructed to drive at a constant speed and steady position within the right hand lane. Results from this work confirm actual outcomes of driving simulator studies: methylphenidate markedly improves driving performance of ADHD patients.

Beliefs about the effects of mixing caffeine and alcohol on hangover or sleep may play a role in motivation to consume these mixtures; therefore, information is needed about actual effects. We investigated whether intoxication with caffeinated vs. non-caffeinated beer differentially affected perceived sleep quality, sleepiness, and hangover incidence and severity the next morning.University students (89%) and recent graduate drinkers were randomized to receive: (1) beer with the equivalent of 69mg caffeine/12oz glass of regular beer (n=28) or (2) beer without caffeine (n=36), in sufficient quantity to attain a BrAC of 0.12g%. After an 8-h supervised sleep period, participants completed measures of hangover, sleep quality, sleep latency and time asleep, and sleepiness.While caffeinated beer improved perceived sleep quality, effect sizes were greater for morning alertness than for quality while sleeping, with no effect on sleep latency or total sleep time. No effects were seen on hangover incidence or severity.Mixing caffeine and alcohol does not significantly impair amount of sleep or sleep latency, hangover, or sleepiness the morning after drinking to intoxication in this population.

Lapses are brief periods of inattention and reduced alertness which may be a risk factor for car crashes. The Dutch on-the-road driving test is applied to examine effects of CNS drugs on driving, using the standard deviation of lateral position (SDLP) as primary outcome measure. This paper examines the utility of an alternative outcome measure, lapses, to determine the degree to which CNS drugs impair driving. Data from two double-blind, placebo-controlled on-the-road driving studies that examined the residual effects of hypnotic drugs were reanalyzed. The treatments were zaleplon and zolpidem tested 4 h after middle-of-the-night administration, and ramelteon and zopiclone tested 8.5 h after bedtime administration. In addition to SDLP, outcome measures related to lapses (number, total duration, and maximum deviation) were computed. A lapse was defined as a continuous change in lateral position of greater than 100 cm, lasting for at least 4 s. Both SDLP and lapses were able to detect significant driving impairment after middle-of-the-night administration of zolpidem (10 and 20 mg) and bedtime administration of ramelteon (8 mg) and zopiclone (7.5 mg) relative to placebo. Both measures found no differences from placebo after middle-of-the-night administration of zaleplon (10 and 20 mg). The number of lapses was more sensitive in differentiating treatment from placebo than the maximum deviation of a lapse or their duration. After considering different lapse duration criteria, a lapse was redefined as a continuous change in lateral position of greater than 100 cm, lasting for at least 8 s. This change in definition did not significantly alter the outcome of the statistical analyses. In addition to SDLP, the number of lapses is a useful outcome measure to identify treatments that impair driving. Future research should determine the unique contributions of SDLP and lapses in defining the potential risk of CNS drugs on driving.

Whether patients with sleep disorders are fit to drive, and who should determine this, is a matter of debate. However, scientific literature is available on these topics to aid clinicians making these decisions. A survey was conducted to assess sleep specialists' views on fitness to drive for patients suffering from apnea, insomnia, and narcolepsy. Most of the 112 respondents (66%, 95%CI: 57-74%) indicated that insomnia patients would be fit to drive within days or weeks after initiating treatment, but 44% (95%CI: 35-53%) felt that, depending on the amount of excessive daytime sleepiness (EDS), they should not drive if untreated. Around half of respondents (49%, 95%CI: 40-58%) indicated that untreated patients with apnea should not drive, but the majority (66%, 95%CI: 57-74%) felt they could drive after Continuous Positive Airway Pressure treatment was established, though EDS was a significant factor. For untreated narcoleptic patients 77% (95%CI: 68-84%) indicated they should not drive, and similarly, that treated patients could drive, although EDS levels were again seen as important. It is concluded that patient education remains the most practical approach to improve compliance and reduce accidents associated with EDS. Sleep specialists should remain up-to-date of relevant scientific literature to achieve this goal. Language: en

To the Editor: In their study “Mixing an Energy Drink with an Alcoholic Beverage Increases Motivation for More Alcohol in College Students,” Marczinski and colleagues (in press) conclude that “An energy drink may elicit increased alcohol priming. This study provides laboratory evidence that AmED beverages may lead to greater motivation to drink versus the same amount of alcohol consume alone.” However, on inspection of the study, we believe that this conclusion is premature and that issues with the design, analysis, and interpretation of the data may merit different conclusions. The first, less serious issue relates to the nature of the vehicle, Squirt, which is described by the manufacturers as a caffeine-free citrus soda. If we assume that the participants had some knowledge of Red Bull, then the sensory characteristics of the vehicle and alcohol compared with energy drink and alcohol mixed with energy drink (AmED) may have produced different expectancies, potentially confounding the main outcomes of the study. The second, more substantive issue relates to the analyses performed. The study utilized a between-subjects design and compared the effects of a placebo (Squirt lemon drink), alcohol, Red Bull energy drink, and AmED. The study includes several subjective measures but focuses on “desire to drink” which was assessed at baseline then at 10, 20, 40, 60, and 80-minutes postdrink. These scores were appropriately subjected to a 2 (Alcohol) × 2 (Energy Drink) × 2 (Gender) × 6 (Time) analysis of variance with time as a repeated measures factor. This revealed a significant interaction (p = 0.046). An appropriate analysis would then be to compare treatment groups at each time point which the authors then did using independent samples t-tests comparing alcohol and AmED groups. The authors state “No differences between alcohol and AmED for any of the time points were observed, although there was a nonsignificant trend for higher ratings for AmED versus alcohol alone at 40 minutes, t(38) = 1.47, p = 0.075.” The between-groups comparison, therefore, failed to reveal any significant effects. In addition to the above, the authors compared, within each group, each time point with their respective baseline scores using paired samples t-tests. Unfortunately, this analysis tells us nothing about the differences between groups (Nieuwenhuis et al., 2011), for example, whether there are any differences between the alcohol and the AmED groups. However, they have used the results of the within-groups analysis to make inferences about differences between groups, even though they have shown these to be nonsignificant. This same analytical approach was used by some of these authors in an earlier study which then also drew erroneous conclusions (Marczinski et al., 2011). Additionally, such analyses can be greatly influenced by chance baseline differences in the same measure and by regression to the mean. Indeed, inspection of baseline “desire for alcohol” ratings (table 1) reveals large variations in mean baseline scores (energy drink 13.00, vehicle 7.80, alcohol 6.65, and AmED 4.65). This reflects sampling variability associated with the study and provides a range estimate (8 units) with which to compare posttreatment differences. From the graph (fig. 1), the maximum differences between alcohol and AmED appear to be of a similar magnitude supporting the lack of significant differences found. These baseline scores directly predict the magnitude (and duration) of apparent change from baseline scores. Thus, using their questionable analyses, the authors report that consumption of Red Bull alone (with the highest baseline score) reduced “desire for alcohol” at 40 and 80 minutes. The alcohol drink increased “desire for alcohol” at 10 and 20 minutes, while the AmED with the lowest baseline score resulted in increased rating, relative to baseline at 10, 20, 40, and 80 minutes. It is notable that the consumption of vehicle alone, with the third lowest baseline score, resulted in significantly higher “desire for alcohol” restricted to 10 minutes postdrink—surely the most remarkable result of the study! Indeed, if these data are taken at face value then surely the fact that drinking citrus-flavored soda primes alcohol craving at all would be the cause of a major health concern. Of course a more realistic interpretation would compare scores between groups and conclude that there are no effects. Despite the fact that there were no significant between-group differences for this measure, at several points in the discussion section the authors state “we observed that a priming dose of AmED increased these desire ratings for a longer time period compared with a priming dose of alcohol alone,” and “…, participants desired more alcohol following AmED compared with alcohol alone, although they liked and felt the 2 types of alcoholic beverages in a similar fashion.” In the discussion section, Marczinski and colleagues (in press) characterize their results as “remarkable” because “Previous research suggests that this amount of caffeine alone would not reliably alter physiological or subjective state” (i.e., typically 46 mg caffeine). Indeed, it has been consistently shown that coadministering caffeine (

It is generally assumed that there are minimal gender differences in the safety and efficacy of central nervous system drugs, as is evidenced by men and women receiving the same drug dosage. There is, however, evidence that drugs may have a differential effect on performance in men and women, given reported differences in pharmacokinetics as well as the presence or absence and severity of adverse effects. It is especially important to verify whether gender differences in performance exist in case of activities that have potentially dangerous outcomes such as driving a car. This review summarizes the current scientific evidence on gender differences in driving performance after treatment with hypnotic drugs.A literature search was conducted to obtain all studies that conducted on-road driving tests to examine the effects hypnotic drugs on driving. Cross-references were checked and technical reports and raw data were obtained, if possible.Fourteen studies were evaluated. Many studies did not allow analyses of gender effects because only women were included. Others did not report data on gender analyses. Technical reports and additional data analyses revealed significant gender differences in driving performance the morning following bedtime administration of flurazepam (30 mg) and after middle-of-the-night administration of zolpidem (10 mg). No significant gender differences were found for ramelteon (8 mg), lormetazepam (1 and 2 mg), zaleplon (10 and 20 mg), and zopiclone (7.5 mg).Although the available data are limited, the results show that significant gender differences have been found for some drugs but not others. Therefore, in the future more research is needed to reveal potential gender differences and to determine what mediates them.

BACKGROUND: Whilst energy drinks improve performance and feelings of alertness, recent articles suggest that energy drink consumption combined with alcohol may reduce perception of alcohol intoxication, or lead to increased alcohol or drug use. This review discusses the available scientific evidence on the effects of mixing energy drinks with alcohol. METHODS: A literature search was performed using the keywords "energy drink and Red Bull(®)" and consulting Medline/Pubmed, PsycINFO, and Embase. RESULTS: There is little evidence that energy drinks antagonize the behavioral effects of alcohol, and there is no consistent evidence that energy drinks alter the perceived level of intoxication of people who mix energy drinks with alcohol. No clinically relevant cardiovascular or other adverse effects have been reported for healthy subjects combining energy drinks with alcohol, although there are no long-term investigations currently available. Finally, whilst several surveys have shown associations, there is no direct evidence that coadministration of energy drinks increases alcohol consumption, or initiates drug and alcohol dependence or abuse. CONCLUSION: Although some reports suggest that energy drinks lead to reduced awareness of intoxication and increased alcohol consumption, a review of the available literature shows that these views are not supported by direct or reliable scientific evidence. A personality with higher levels of risk-taking behavior may be the primary reason for increased alcohol and drug abuse per se. The coconsumption of energy drinks being one of the many expressions of that type of lifestyle and personality. Language: en

A consumer satisfaction study was conducted to examine the effectiveness on hangover of After-Effect©, a new food supplement dedicated to improve well-being after an occasion of alcohol consumption.N=113persons were invited to participate in a home-based open label study to test the effectiveness of After-Effect©. On a night when they intended to consume alcohol, three pills were taken before alcohol consumption and two pills afterwards, before going to bed. The following day, participants completed a survey on the amount of alcohol consumed, hangover symptom severity, and satisfaction of the product.N=103participants completed the study. 88% of participants reported After-Effect©to be effective in reducing alcohol hangover. After-Effect©significantly improved overall hangover severity, and all individual hangover symptoms, except for palpitations. In addition, a significant reduction (P=0.0001) in the severity score on concentration problems was reported when using After-Effect©. No gender differences were observed, and there was no relationship with the number of alcoholic drinks that were consumed. Consumers were satisfied with the product. In conclusion, consumer satisfaction and hangover severity scores suggest that After-Effect©may be effective in reducing alcohol hangover. However, controlled, double-blind clinical trials should confirm these findings.

Summary Background The use of benzodiazepine receptor agonists can significantly impair driving performance. The aim of this review was to determine if there is a relation between blood concentrations of these drugs and the degree of driving impairment. Methods A literature search was conducted to identify driving studies that examined the effects of benzodiazepine receptor agonists. Studies were included if the on-the-road driving test was employed, using the standard deviation of lateral position (SDLP), i.e., the weaving of the car, as primary outcome measure. Results A total of 24 studies were identified that employed the on-the-road driving test to examine driving performance after administration of benzodiazepine receptor agonists. Eleven of these studies (45.8%) measured blood drug concentrations after the on-the-road driving test was performed. Technical reports of some of these studies provided individual data on blood drug concentrations and ΔSDLP (the ΔSDLP difference between drug and placebo). While group differences in concentrations were found as evidenced by significant effects of dose and time of driving since time of drug ingestion, no significant relationship between individual blood drug concentrations and ΔSDLP was found in any of the studies. Conclusion While group mean average ΔSDLP and blood drug concentration sometimes correlate, individual differences in blood drug concentrations of benzodiazepine receptor agonists correlate poorly with driving impairment. From the currently available data, it must be concluded that there are no significant relationships between individual blood drug concentration and ΔSDLP. Future driving studies should assess blood drug levels as a standard procedure, to enable further research into the relationship between blood drug concentration and performance impairment.