Clinical impairment of benzodiazepines—relation between benzodiazepine concentrations and impairment in apprehended drivers
Introduction
Benzodiazepines are drugs which are widely used as anxiolytics and hypnotics and which also have additional medical indications (Ballenger, 2001, McCall, 2001, Treiman, 2001). They are commonly abused drugs. At any one time an estimated 5% of the population are taking these drugs on legal prescription (Ashton and Golding, 1989, Olfson and Pincus, 1994, Taylor et al., 1998, Naja et al., 2000). In drivers apprehended for impaired driving, 10–15% will have benzodiazepines in their blood when tested (Christophersen and Mørland, 1997, Mørland, 2000).
The National Institute of Forensic Toxicology (NIFT) analyses all blood samples from Norwegian drivers suspected of driving under the influence of alcohol or drugs. This drug analysis has shown that medicinal drugs are detected at supratherapeutic concentrations (Christophersen et al., 2002, Skurtveit et al., 2002), that non-alcoholic drugged driving is becoming more common (Christophersen and Mørland, 1997), that legal drugs are often combined with illicit drug use (Bramness et al., 1999, Bramness et al., 2000), and the presence of frequent multiple drugs use (Skurtveit et al., 1995a, Skurtveit et al., 1995b).
Most research on the concentration–effect relationship of benzodiazepines has been performed with healthy volunteers given moderate doses of the drugs. In such studies benzodiazepines have shown a deteriorating effect on psychomotor performance and cognitive function after acute intake (Ingum et al., 1992, Ingum et al., 1993). An almost linear relationship between blood-drug concentration and its effects was found for benzodiazepines such as diazepam, oxazepam, nitrazepam, flunitrazepam, alprazolam and triazolam when results from several experimental studies were compiled (Berghaus and Grass, 1997).
There is less research into the concentration–effect relationship amongst experienced benzodiazepine users. Tolerance is known to develop more rapidly for hypnotic sedative effects than for anticonvulsant and anxiolytic effects (File, 1985). Also for motor effects there appears to be a development of tolerance in animal models (Khanna et al., 1998). Few have studied psychomotor impairment after acute intake of benzodiazepines in chronic benzodiazepine users (Linnoila et al., 1983, van Laar et al., 1992, O'Hanlon et al., 1995, Mørland, 2000).
In Norway physicians perform a clinical test for drunkenness (CTD) shortly after apprehending drivers suspected of driving under the influence of non-alcoholic drugs. The test was developed simultaneously in several countries from the 1940s onwards (Alha, 1951), and was based more on clinical experience than on scientific principles. The test is possibly less sensitive than more sophisticated psychomotor examinations and may only reveal impairment on a higher level of intoxication (Kuitunen et al., 1990a, Kuitunen, 1994, Kuitunen et al., 1994a).
The present study investigated whether the blood-drug concentration levels of benzodiazepines detected in a population who had taken benzodiazepines at diverging times and in varying doses was related to a physician's conclusion of “not impaired” or “impaired” as assessed by CTD. A similar approach was used on a reference group of drunken drivers to address the same question regarding blood-alcohol concentrations (BAC) and a physician's conclusion as assessed by CTD.
Section snippets
Material
All the present data were taken from an existing register at NIFT and were handled anonymously by the researchers.
Of approximately 90,000 blood samples pertaining to cases of suspected driving under the influence, sent to NIFT in the period 1987–1998, approximately 9500 samples contained benzodiazepines. Of these, 1201 samples containing only one benzodiazepine were drawn for further study. In these 1201 cases no other drugs or alcohol were detected after an immunological screening,
Background variables
The background characteristics of our material are presented in Table 2. Except for expected gender differences with respect to BMI, the only difference between male and female drivers was that female drivers, were on average, older than male drivers (P<0.01).
The mutual dependencies between the background variables were studied in detail (data not shown). Age correlated with BMI (Pearson's r=0.172, P<0.001). The drivers who admitted to regular use of drugs did not differ from those who did not,
Main findings
Impaired subjects had significantly higher blood levels of diazepam, oxazepam and flunitrazepam than those not impaired. For all benzodiazepines combined with the drug levels categorized as “therapeutic”, “mildly”, “moderately” or “highly elevated” the risk of being assessed as impaired did rise with increasing benzodiazepine-blood level. A significantly higher risk of being judged impaired was also found in the groups with elevated blood-drug concentrations after adjustments were made for
Conclusion
We found a clear concentration–effect relationship as measured by benzodiazepine drug concentrations and clinically assessed impairment, despite the limitations discussed above. This relationship is maintained when adjustment is made for background variables. The relationship is of a similar magnitude to that found in the reference group of drunken drivers, at least for mildly and moderately elevated BAC.
Like Norway most European countries have legislation for drugged driving using the
Acknowledgements
The authors thank Merete Grung, Margaretha Gulliksen, Jon Ivar Wethe and Philip Skau for work on collecting the material and preparing it for data analysis. We also wish to thank the late Johan Sakshaug for the use of the material on BAC in apprehended drivers in 1987. This research was done without external financing. None of the authors have any conflict of interest that could influence the present research.
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2013, Accident Analysis and PreventionCitation Excerpt :In their review of research on the risks associated with the use of medicinal drugs, Orriols et al. (2009) also concluded that BZD use is associated with an increased risk of accident, with no evidence of any such risk for other medicinal drugs. It has been argued that the higher the BZD blood concentration, the higher the proportion of drivers assessed as impaired, which is reminiscent of the relationship between alcohol and impairment (Bramness et al., 2002; Vermeeren et al., 2002; Smink et al., 2008; Gustavsen et al., 2009). The purpose of this study was thus to explore the effects of BZDs on driving safety, focusing on the trajectory control component of driving performance (i.e., lane-keeping).