Recent statistics reveal that more than 40000 people die on European roads each year, and another 1.7 million are injured. About a quarter of these deaths, some 10000 per year, are estimated to be caused by drink driving. Although alcohol is by far the most prevalent psychoactive substance affecting drivers, concerns have been mounting about the role of medicinal drugs to motor vehicle crashes. In a recent review of drug driving research conducted by The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) recently published a literature review of drug driving research (EMCDDA 2008). In general, drug driving research has followed to methodological approaches (i.e. experimental and epidemiological) that are mutually supportive. Experimental studies aim to assess medicinal drug effects after controlled administration in actual driving tests, driving simulator tests or laboratory measures of skills related to drivers. Epidemiological studies aim to measure accident involvement of drivers who are receiving medicinal drug treatment. In experimental studies, the primary outcome measure is (performance) impairment. In epidemiological studies, the primary outcome measure is crash risk. Experimental research on individual drug effects is more prevalent in the scientific literature as compared to epidemiological work. Ideally both experimental and epidemiological research should be conducted on individual drug effect on driver safety. Unfortunately however, the combination of epidemiological and experimental data on traffic safety is simply lacking for most medicinal drugs. To date, only 2 drug classes have been consistently shown to increase driver impairment and crash in both experimental and epidemiological studies respectively. These drug classes are: benzodiazepines and tricyclic antidepressants. For other medicinal drug classes only experimental data is available. In general, the most important conclusions from the EMCDDA review regarding medicinal drugs effects on driving performance were: * Benzodiazepines generally have impairing effects, but some types (whether long-, medium- or short-acting) cause severe impairment, while others are unlikely to have residual effects the following day. * First-generation antihistamines are generally more sedating than second-generation ones, though there are exceptions in both groups. * Tricyclic antidepressants show more impairment than the more recent types, though the results of experimental tests after consuming second-generation selective serotonin reuptake inhibitors are not always consistent. * In every therapeutic class, some substances are associated with little or no impairment. These therapeutic drugs should preferably be prescribed to those wishing to drive. For many other CNS drugs, information on crash risk or driver impairment is still lacking. For such drugs, evaluation of their impairing potential primarily depends on the evaluation of its pharmacological profile. A drug that is known to induce side effects relevant to driving, e.g. drowsiness, sedation, lack of concentration, is likely to be classified as an impairing drug in categorization systems for medicinal drugs and driving. Such classification systems thus generally include more potentially impairing medicinal drugs than those commonly found in experimental and epidemiological literature. From this point of view it is very interesting that a French research group (Orriols et al 2010) recently published a registry based study in 72685 drivers on the association between medicinal drug use and crash risk group for 4 separate risk levels that are distinguished in the French medication categorization system. These warning/risk levels include: no risk of impairment (level 0); be careful, read leaflet before driving (level 1); be very careful, to active advise from physician before driving (level 2) and danger, do not drive (level 3). Level 2 and level 3 medicines included a large number of CNS medicinal drugs such as opioids, antiepileptics, antipsychotics, antiparkinsonian drugs, antidepressant, anxiolytics and hypnotics (including benzodiazepines), antihistamines and drugs used in alcohol dependence. The fraction of road traffic crashes that were attributable to drugs classified in levels 2 and 3 was 3.3%. Users of level 2 (OR=1.31[1.24-1.4]) and level 3 (OR= 1.25 [1.12-1.4]) drugs were more likely to be responsible for their crash A within-person case-control analysis furthermore showed that drivers were more likely to be exposed to level 3 medications on the crash day as compared to a control day (OR=1.15 [1.05-1.27]). This study nicely demonstrates that the use of a large range of medicinal drugs is associated with a significant increase in road crashes. It offers the perfect rationale for conducting more experimental and epidemiological drug driving research in order to identify medicinal drugs that have “impairing potential” of individual drugs that significantly increase crash risk and of contributing factors that may further increase the risk of become involved in traffic accidents, such as concomitant use of drugs and alcohol, treatment duration or treatment dose. The studies presented in this deliverable were all designed from to assess medicinal drug effects, covering a range of drug classes, on actual or simulated driving performance. Individual drugs that were selected for research belonged to one of the following drug classes. (Author/publisher) This document is available at https://www.bast.de/Druid/EN/Home/home_node.html
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