Driving performance under alcohol in simulated representative driving tasks: an alcohol calibration study for impairments related to medicinal drugs.

Comparing drug-induced driving impairments with the effects of benchmark blood alcohol concentrations (BACs) is an approved approach to determine the clinical relevance of findings for traffic safety. The present study aimed to collect alcohol calibration data to validate findings of clinical trials that were derived from a representative test course in a dynamic driving simulator. The driving performance of 24 healthy volunteers under placebo and with 0.05% and 0.08% BACs was measured in a double-blind, randomized, crossover design. Trained investigators assessed the subjects' driving performance and registered their driving errors. Various driving parameters that were recorded during the simulation were also analyzed. Generally, the participants performed worse on the test course (P < 0.05 for the investigators' assessment) under the influence of alcohol. Consistent with the relevant literature, lane-keeping performance parameters were sensitive to the investigated BACs. There were significant differences between the alcohol and placebo conditions in most of the parameters analyzed. However, the total number of errors was the only parameter discriminating significantly between all three BAC conditions. In conclusion, data show that the present experimental setup is suitable for future psychopharmacological research. Thereby, for each drug to be investigated, we recommend to assess a profile of various parameters that address different levels of driving. On the basis of this performance profile, the total number of driving errors is recommended as the primary endpoint. However, this overall endpoint should be completed by a specifically sensitive parameter that is chosen depending on the effect known to be induced by the tested drug.

Effects of oxcarbazepine and carbamazepine on driving ability: a double-blind, randomized crossover trial with healthy volunteers.

RATIONALE: Carbamazepine (CBZ) is known to produce cognitive side effects being at least partly relevant for driving. In contrast to this, the cognitive effects of oxcarbazepine (OXC) are suspected to be less pronounced. OBJECTIVE: This study aimed to test 900 mg/day OXC as compared to 600 mg/day CBZ with respect to driving. METHODS: Driving performance of 27 healthy volunteers under subchronic treatment of OXC and CBZ was assessed in a driving simulator with a double-blind, randomized, crossover design including a baseline measurement. The test course contained a representative set of scenarios. Lane-keeping performance, driving mistakes, and eyelid closure (as a behavioral measure of sleepiness) were analyzed. In addition, subjects were asked to assess their driving performance, effort, attention, and sleepiness subjectively. RESULTS: Both drugs had negative effects on driving as reflected in poorer lane-keeping performance, higher rate of driving mistakes, increased sleepiness, and worse subjective ratings. These effects were most obvious in monotonous situations and could be compensated in situations challenging to cognitive and motor driving skills. With respect to all considered parameters, CBZ did more often differ significantly from baseline than OXC. CONCLUSIONS: Under both drugs, driving performance was worse than at baseline. Even though deterioration of driving performance was only slightly less pronounced under OXC than under CBZ, it might be recommended as more appropriate than CBZ for epileptic patients who need to drive a car.

Developing limits for driving under cannabis.

OBJECTIVE: Development of a rational and enforceable basis for controlling the impact of cannabis use on traffic safety. METHODS: An international working group of experts on issues related to drug use and traffic safety evaluated evidence from experimental and epidemiological research and discussed potential approaches to developing per se limits for cannabis. RESULTS: In analogy to alcohol, finite (non-zero) per se limits for delta-9-tetrahydrocannabinol (THC) in blood appear to be the most effective approach to separating drivers who are impaired by cannabis use from those who are no longer under the influence. Limited epidemiological studies indicate that serum concentrations of THC below 10 ng/ml are not associated with an elevated accident risk. A comparison of meta-analyses of experimental studies on the impairment of driving-relevant skills by alcohol or cannabis suggests that a THC concentration in the serum of 7-10 ng/ml is correlated with an impairment comparable to that caused by a blood alcohol concentration (BAC) of 0.05%. Thus, a suitable numerical limit for THC in serum may fall in that range. CONCLUSIONS: This analysis offers an empirical basis for a per se limit for THC that allows identification of drivers impaired by cannabis. The limited epidemiological data render this limit preliminary.

Predictors of freezing in Parkinson's disease: a survey of 6,620 patients.

Data from a survey of 6,620 Parkinson's disease patients were examined for correlation of freezing with age, sex, duration, subjective severity of Parkinson's disease, and antiparkinsonian medication. Forty-seven percent of the patients reported experiencing freezing regularly. Logistic regression analysis showed that freezing was significantly associated with a longer disease duration and a more advanced stage of the disease. Freezing episodes were more likely in men than in women and in patients taking, in addition to levodopa, Entacapone, Amantadine, or dopamine agonists. Finally, patients considering tremor as their main symptom reported freezing less frequently. Common antiparkinsonian drugs given in combination with levodopa were not negatively correlated with freezing. The results underline the necessity to develop appropriate countermeasures against this phenomenon, which is widely known to cause significant impairment of patients' quality of life and - as our data also showed - may cause traffic accidents in licensed patients.

Sudden onset of sleep and dopaminergic therapy in patients with restless legs syndrome.

BACKGROUND AND PURPOSE: Sudden onset of sleep (SOS) was recently reported in patients with Parkinson's disease (PD) under dopaminergic treatment. Here, we investigated as to what extent SOS is found in patients with restless legs syndrome (RLS), who are frequently treated with dopaminergic drugs, and controls. PATIENTS AND METHODS: A questionnaire survey on SOS was administered to 156 RLS patients and 126 controls. RESULTS: While no significant difference between RLS patients and controls was detected in Epworth sleepiness scale (ESS) scores (P=0.76), the prevalence of SOS was higher in RLS patients (32.7%) than in controls (19.8%) (P=0.02). Significant predictors of SOS in RLS were ESS score (odds ratio (OR) 16.4), male sex (OR 4.6), duration of night-time sleep (OR 3.0), and age (OR 2.9), while no association was observed for duration or severity of the disease. Patients on dopaminergic therapy usually featured a lower risk of SOS than untreated patients. Falling asleep while driving was reported by 14.6% of all RLS patients with a driver's license and associated with increased risk of accident (OR 7.1). CONCLUSIONS: RLS patients who are untreated, male, and elderly should be assessed for the presence of SOS. In contrast to PD, dopaminergic drugs may reduce the risk of SOS in RLS. The possible benefit of the drugs should be investigated particularly in male patients.

Daytime sleep latency in medication-matched Parkinsonian patients with and without sudden onset of sleep.

Currently, it is unclear whether sleep attacks in Parkinson's disease (PD) represent a novel entity or just a phenomenon of daytime sleepiness. We investigated 10 PD patients with sleep attacks and compared them with 10 PD patients without any daytime sleepiness. The patients were matched according to their dopaminergic medication and subjected to a sleep medical investigation. The mean sleep latency on the multiple sleep latency test was in the normal range and not significantly different between the groups. These data suggest that sleep attacks can occur against a background of normal alertness.

Driving in Parkinson's disease: mobility, accidents, and sudden onset of sleep at the wheel.

Only few studies have addressed driving ability in Parkinson's disease (PD) to date. However, studies investigating accident proneness of PD patients are urgently needed in the light of motor disability in PD and--particularly--the report of "sleep attacks" at the wheel. We sent a questionnaire about sudden onset of sleep (SOS) and driving behavior to 12,000 PD patients. Subsequently, of 6,620 complete data sets, 361 patients were interviewed by phone. A total of 82% of those 6,620 patients held a driving license, and 60% of them still participated in traffic. Of the patients holding a driving license, 15% had been involved in and 11% had caused at least one accident during the past 5 years. The risk of causing accidents was significantly increased for patients who felt moderately impaired by PD, had an increased Epworth Sleepiness Scale (ESS) score, and had experienced SOS while driving. Sleep attacks at the wheel usually occurred in easy driving situations and resulted in typical fatigue-related accidents. Those having retired from driving had a more advanced (subjective) disease severity, higher age, more frequently female gender, an increased ESS score, and a longer disease duration. The study revealed SOS and daytime sleepiness as critical factors for traffic safety in addition to motor disabilities of PD patients. The results suggest that real sleep attacks without any prior sleepiness are rare. However, our data underline the importance of mobility for patients and the need for further studies addressing the ability to drive in PD.

Dopamine receptor gene polymorphisms in Parkinson's disease patients reporting "sleep attacks".

Genes encoding proteins involved in dopaminergic transmission are potential candidate genes for the induction of somnolence in Parkinson's disease (PD) because dopaminergic agents have been shown to be associated with sudden onset of sleep (SOS) in PD. We conducted an association study on dopamine D2, D3, and D4 receptor gene polymorphisms comparing 137 PD patients with SOS and 137 PD patients without SOS matched according to drug therapy, disease duration, sex, and age. Our results show a significant association between the dopamine D2 receptor gene polymorphism Taq IA and SOS in PD. No significant association between two other investigated polymorphisms and the phenomenon of "sleep attacks" in PD was observed.

Predictors of sudden onset of sleep in Parkinson's disease.

With respect to the ongoing discussion of "sleep attacks" in Parkinson's disease (PD), we sought to estimate the prevalence of sudden onset of sleep (SOS) with and without preceding sleepiness in PD, to identify associated factors, and to define the role of antiparkinsonian medication in SOS. We sent a questionnaire about SOS, sleep behaviour, and medication to 12,000 PD patients. The response rate was 63%, from which 6,620 complete data sets could be analysed. A total of 42.9% of our population reported SOS, 10% of whom never experienced sleepiness before the appearance of SOS (4.3% of all), and we identified the administration of all dopaminergic drugs as a risk factor for SOS. However, SOS occurred earlier after introduction of nonergoline dopamine agonists (DA) and was more strongly associated with nonergoline DA in younger patients (below 70 years) with a shorter disease duration (up to 7 years) but, actually, medication was less efficient in predicting SOS than most other factors considered such as higher age, male sex, longer disease duration, and the report of sleep disturbances. This survey strongly suggests that SOS is a multifactorial phenomenon. Some subgroups are at particular risk of experiencing SOS under nonergoline DA, especially at the beginning of this therapy. Our results support the current notion that SOS, in part, can be attributed to PD-specific pathology because disease duration and subjective disease severity have been shown to be predictors of SOS. We recommend the development of a standardised question to recognise SOS and to facilitate the comparison of prevalence estimates.

How the presence of passengers influences the risk of a collision with another vehicle.

The risk of a collision with another vehicle due to the presence of passengers is analysed in detail in a large sample of accidents from Mittelfranken, Germany, from the years 1984 to 1997. Using a responsibility analysis, the overall effect of the presence of passengers and the influence of modifying variables is examined. While a general protective effect of the presence of passengers is found, this is reduced in young drivers, during darkness, in slow traffic and at crossroads, especially when disregarding the right of way and passing a car. These findings are interpreted as a general positive effect of the presence of passengers who influence the driver's behaviour towards more cautious and thus safer driving behaviour. However, passengers may also distract drivers' attention in an amount which cannot be compensated for in all situations and by all drivers by cautious driving. Besides educational measure, a potential solution to this problem may be driver assistance systems which give an adapted kind of support when passengers are present.