EFFECTS ON DRIVING ABILITY
Visual, cognitive, or psychomotor impairments associated with a range of drug groups and specific drug combinations have been investigated. Although several drug groups are represented, interactions among drugs that affect the central nervous system are the most common. There are, however, relatively few studies that report the effects of combinations of mediations specifically on driving performance, although some related studies do provide insight. For example, a history of falls is associated with difficulty in driving (Lyman et al., 2001), and falls in the elderly are associated with the use of psychotropic drugs (Riefkohl, Bieber, Burlingame, and Lowenthal, 2003). In patients who failed to respond to treatment with the SSRI paroxetine and who received augmentation therapy with bupropion,34 an increased risk of falls was seen (Joo et al., 2002). Katona (2001) has reviewed briefly drug interactions that occur with psychotropic drugs, including antidepressants, mood stabilizers, antipsychotics, and cholinesterase inhibitors. Indeed, the concomitant use of the cholinesterase inhibitor donepezil and other anticholinergics was found to be relatively common in a cohort of community-based older adults with probable dementia (Roe, Anderson, and Spivack, 2002).
As indicated elsewhere in this document, the use of sedating antidepressants is associated with driving impairment in the elderly (Ramaekers, 2003). A recent review notes a large number of clinically significant drug interactions with antidepressants in the elderly (Spina and Scordo, 2002); for example, tricyclic antidepressants and monoamine oxidase inhibitors have a high potential for pharmacodynamic drug interactions with a range of drugs, including benzodiazepines, antipsychotic agents, and other antidepressants. The newer antidepressants, such as SSRIs, SNRIs, and so-called dual-action compounds, e.g., mirtazepine, exhibit fewer drug interactions than the sedating antidepressants and long-acting benzodiazepines, but pharmacokinetic drug interactions may be seen (Sheikh, 2004). Orthostatic hypotension35 is an adverse effect seen with some antidepressants, particularly the tricyclic antidepressants and some of the so-called atypical antidepressants (Keene, Galasko, and Land, 2003). Some medications that may be prescribed along with antidepressants that may increase the risk of dizziness, syncope, and falling include antipsychotics, anxiolytics, hypnotics, opioid analgesics, diuretics, and other antihypertensive medications.
Benzodiazepine use is widespread among older adults (Gray et al., 2003); in a population of 1,505 enrollees in a health-maintenance organization (average age of 72.5; 59% female), the prevalence and incidence of benzodiazepine use was 12.3 percent and 6.6 percent, respectively. In a cohort of 78,367 elderly subjects (average age of 73.6; 55.7% female) in Quebec, Canada, 45 percent filled a prescription for a benzodiazepine ( Bartlett, Abrahamowicz, Tamblyn, Grad, Capek, and du Berger, 2004). The mean duration of benzodiazepine use was 75.5 days.
Although the risks for traffic crashes associated with the use of benzodiazepines and related compounds have been established (for a review, see Vermeeren, 2004), little information is available about the interaction of benzodiazepines and other drugs, except alcohol. In a study of 269 patients involved in traffic crashes and admitted to the emergency room of the University Hospital of Trauma Surgery in Innsbruck, Austria, both alcohol and a benzodiazepine was present in the blood of 2.3 percent of the patients older than 60 (Kurzthaler et al., 2003). All plasma benzodiazepine concentrations were stated to be within the therapeutic range. A combination of both alcohol and psychotropic drugs was found to be involved in approximately 10 percent of the cases in a study of 3,398 fatal motor vehicle crashes in three Australian states, but the data did not allow assessment of the role of benzodiazepines (Drummer et al., 2003; Drummer et al., 2004).
In a study in The Netherlands, benzodiazepines were found to increase the risk of motor vehicle crashes. The adjusted odds ratio for benzodiazepine use amounted to 5.1 (95% CI: 1.8–14.0). Although 14 percent of the subjects in the 110 cases studied were 50 or older, the incidence of the use of both alcohol and benzodiazepines in this age group was not reported (Movig et al., 2004).
The roles of medical conditions and medications in automobile crashes in the elderly have been investigated (McGwin, Sims, Pulley, and Roseman, 2000). The cohort included 901 drivers in Alabama, and of these, there were 244 at-fault drivers, 182 not-at-fault drivers, and 475 drivers not involved in crashes. Older drivers (65 or older; 50.4 percent females) with heart disease or stroke were more likely to be involved in at-fault automobile crashes; benzodiazepine use was also associated with at-fault crash involvement (OR = 5.2, CI = 0.9–30.0), but the involvement of both benzodiazepines and other drugs was not reported.
A review of 170 positive lorazepam36 drug-impaired driving cases in Washington was conducted (Clarkson, Gordon, and Logan, 2004) . Eighty-six percent of the drivers tested positive for other drugs in addition to lorazepam, including muscle relaxants (meprobamate, carisoprodol), painkillers (methadone, hydrocodone), and alcohol; the contribution of the other drugs to drug-impaired driving was not investigated, and the ages of the drivers who tested positive for lorazepam and other drugs were not reported.
Del Rio and Alvarez (2003) evaluated the relationship between medicinal drug use and fitness to drive for 8,043 drivers attending Medical Fitness to Drive Test Centers. Spain is the only country in the European Union where it is compulsory for all new and renewing drivers to take a medical-psychological test prior to licensure. In the Medical Driving Test Centers, medical, eyesight, and psychological tests are conducted to assess fitness to drive ( del Rio and Alvarez, 2001). Road tests are not part of the battery. A team of professionals working in the centers is comprised of a general practitioner, an ophthalmologist, and a psychologist. These professionals analyze aspects of sight, hearing, the locomotor system, cardiovascular diseases, diabetes mellitus, neurological disease, mental disorders, problems relating to alcohol, drugs, and medicinal products, and renal disorders. In addition, the following perceptual-motor skills are evaluated: time-movement anticipation, senso-motor coordination, and multiple reaction times. As a result of the evaluation, drivers are classified as either fit, fit with restrictions (e.g., medical-psychological check-up required at regular intervals, more frequent intervals, or vehicle adaptation), suspended for a period of time, or unfit (permission to drive is irrevocably refused for medical, psychological, or ophthalmologic reasons).
Analyses reported by del Rio and Alvarez (2003) showed that 24.7 percent of the drivers chronically consumed medications (used them daily for at least one month) with men consuming more medications, and medication use increasing with increases in age. Fifty-six percent of the drivers 65 and older took medications on a daily basis, and 25 percent of these reported taking medicines and drinking alcohol daily. The mean number of medications consumed among chronic users across all age groups was 1.28. The mean number consumed by drivers 65 and older was 1.42. The therapeutic groups most frequently consumed were: cardiovascular system (7.8 percent of the sample), followed by alimentary tract and metabolism (4.8 percent), and central nervous system (4.3 percent). For 20 percent of the medication-used-chronically group, there was a warning in the Summary of Product Characteristics about the effect of the medication on driving. Of the drivers considered “fit,” 22 percent were taking medications with a warning. Of those considered “fit with restrictions,” 38 percent were taking medications with a warning. Of the drivers considered “suspended,” 51 percent were taking medications with a warning. Of the drivers who were taking medicines chronically and were deemed “unfit to drive,” 100 percent (n=9) were taking medications that had a warning about driving. All nine also suffered from a pathology that could interfere with fitness to drive. The medications being taken by the nine subjects deemed “unfit to drive” were as follows (with three of the nine cases also having a diagnosed dependence on alcohol):
The percentage of “unfit to drive” cases increased with the number of medications consumed (1 drug = 0.3%, 2 drugs = 0.5%, 3 drugs = 1.2 %, and 4 drugs 9.1 %) as did the percentage of those found “fit with restrictions” (1 drug = 16.2%, 2 drugs = 21.2%, 3 drugs = 43.2%, and 4 drugs = 45.3%).
In Leroy’s (2004) case-control analysis using a pharmaceutical claims database with codes indicating services rendered as the result of a motor vehicle crash, higher percentages of crash-involved drivers were prescribed two or more prescriptions than non-crash-involved drivers. Potentially driver-impairing (PDI) medicines were used by greater percentages of crash-involved drivers than by non-crash-involved drivers (e.g., narcotic analgesics, skeletal muscle relaxants, anti-anxiety medications, NSAIDs, and COX inhibitors). The most-frequently appearing drug combinations (in descending order of frequency) in the group of crash-involved drivers 50 and older were:
Preliminary results of Leroy’s (2004) analysis indicate that 64 percent of the drivers 50 and older who had a motor vehicle crash had received a prescription for a potentially driver-impairing (PDI) medication within the prior 60 days. This compares to 54 percent of the non-crashed involved drivers 50 and older. To qualify as a PDI medication, the medication had to be associated with known effects on the central nervous system, blood sugar levels, blood pressure, vision, or otherwise have the potential to interfere with driving skills. Possible PDI effects include sedation, hypoglycemia, blurred vision, hypotension, dizziness, fainting (syncope), and loss of coordination (ataxia). Preliminary results are suggestive that the following medications are impairing and related to crash risk: narcotic analgesics, antidepressants, antidiabetic agents, anti-anxiety agents, antihypertensive agents, and skeletal muscle relaxants.
In a study conducted in Spain by del Rio, G ómez, Sancho, and Alvarez (2002), some type of psychoactive drug was detected in 50.1 percent of the 5,745 drivers killed in traffic crashes between 1991 and 2000, with alcohol the most prevalent (43.8%), followed by illicit drugs (8.8%) and medicinal drugs (4.7%). Among the medicinal drugs were benzodiazepines (3.4%), antidepressant drugs (0.6%), and analgesics (0.4%). In the sample, 92 percent were males and 8 percent were females; 10 percent were under age 20, 31 percent were between 21 and 30, 19 percent were between 31 and 40, 13 percent were between 41 and 50, 9 percent were between 51 and 60, and 11 percent were over 60. Age was unknown in the remaining 7 percent. Blood samples were analyzed for alcohol. All samples were also screened for the presence of illicit and medicinal drugs. Positive results after screening were confirmed by gas chromatography—mass spectrometry (GC—MS) and concentrations of psychoactive drugs or metabolites were determined.
Results indicated that in 49.9 percent of the cases (2,868), no substance was detected, and in 50.1 percent of the cases (2,877) some type of psychoactive substance was detected. Of the cases in which some psychoactive substance was detected, the following combinations of substances were found:
Considering the 4.7 percent (269 of the 5,745 drivers) with medicinal drugs, the following combinations were found:
In 59.1 percent (159 of the 269) cases in which medicines were found, alcohol and/or illicit drugs were present. In 18 of the 110 cases in which only medicines were detected, two or more medicines were present. Benzodiazepines represented the most commonly detected group of medicines, followed in decreasing order by antidepressants, analgesic, anti-epileptic drugs, barbiturates, H-1 antihistamines, vasodilators, calcium antagonists, antihemetic drugs, and anti-psychotic drugs. Benzodiazepines were detected alone in 27.6 percent of the cases in which medicine was found. When benzodiazepines were detected with other substances (in 72.4% of the cases), they were found along with illegal drugs in 41.3 percent of the cases, with alcohol in 33.7 percent of the cases, and with other medicines in 14.8 percent of the cases.
36 Lorazepam (brand name: Ativan) is a benzodiazepine with CNS depressant, anxiolytic and sedative properties, used to relieve anxiety. Lorazepam is also used to treat irritable bowel syndrome, epilepsy, insomnia, and nausea and vomiting from cancer treatment, and to control agitation caused by alcohol withdrawal.