Driving performance of long-term users of sedating antidepressants and benzodiazepines.

OBJECTIVE: Using benzodiazepines and certain antidepressants is associated with an increased risk of motor vehicle crashes due to impaired driving skills. Hence, several countries prohibit people who use these drugs from driving. Traffic regulations for driving under the influence of these drugs are, however, largely based on single-dose studies with healthy participants. The effects of drugs on chronic users may be different because of potential development of tolerance or by adapting behavior. In this study, we test the effects of anti-depressants, hypnotics, or anxiolytics use on driving performance in patients who use these drugs for different durations and compare the effects to healthy controls' performance. METHODS: Sixty-six healthy controls and 82 medication users were recruited to perform four drives in a driving simulator. Patients were divided into groups that used anti-depressants, hypnotics, or anxiolytics, for shorter or longer than 3 years (i.e. LT3- or LT3+, respectively). The minimum term of use was 6 months. Driving behavior was measured in terms of longitudinal and lateral control (speed variability and Standard Deviation of Lateral Position: SDLP), brake reaction time, and time headway. Impaired driving performance was defined as performing similar to driving with a Blood Alcohol Concentration of 0.5‰ or higher, determined by means of non-inferiority analyses. RESULTS: Reaction time analyses revealed inconclusive findings in all groups. No significant performance differences between matched healthy controls, LT3- (n = 2), and LT3+ (n = 8) anxiolytics users were found. LT3+ antidepressants users (n = 12) did not perform inferior to their matched controls in terms of SDLP. LT3- hypnotics users (n = 6) showed more speed variability than their matched healthy controls, while this effect was not found for the LT3+ group (n = 14): the latter did not perform inferior to the healthy controls. Regarding Time Headway, no conclusions about the LT3- hypnotics group could be drawn, while the LT3+ group did not perform inferior compared to the control group. CONCLUSIONS: The small number of anxiolytics users prohibits drawing conclusions about clinical relevance. Although many outcomes were inconclusive, there is evidence that some elements of complex driving performance may not be impaired (anymore) after using antidepressants or hypnotics longer than 3 years.

On-the-road driving performance of patients with central disorders of hypersomnolence.

INTRODUCTION: Excessive Daytime Sleepiness is a core symptom of narcolepsy and idiopathic hypersomnia, which impairs driving performance. Adequate treatment improves daytime alertness, but it is unclear whether driving performance completely normalizes. This study compares driving performance of patients with narcolepsy and idiopathic hypersomnia receiving treatment to that of healthy controls. METHODS: Patients diagnosed with narcolepsy type 1 (NT1, n = 33), narcolepsy type 2 (NT2, n = 7), or idiopathic hypersomnia (IH, n = 6) performed a standardized one-hour on-the-road driving test, measuring standard deviation of lateral position (SDLP). RESULTS: Results showed that mean SDLP in patients did not differ significantly from controls, but the 95%CI of the mean difference (+1.02 cm) was wide (-0.72 to +2.76 cm). Analysis of subgroups, however, showed that mean SDLP in NT1 patients was significantly increased by 1.90 cm as compared to controls, indicating impairment. Moreover, four NT1 patients requested to stop the test prematurely due to self-reported somnolence, and two NT1 patients were stopped by the driving instructor for similar complaints. CONCLUSION: Driving performance of NT1 patients may still be impaired, despite receiving treatment. No conclusions can be drawn for NT2 and IH patients due to the low sample sizes of these subgroups. In clinical practice, determination of fitness to drive for these patients should be based on an individual assessment in which also coping strategies are taken into account.

A pooled analysis of on-the-road highway driving studies in actual traffic measuring standard deviation of lateral position (i.e., "weaving") while driving at a blood alcohol concentration of 0.5 g/L.

INTRODUCTION: The on-the-road highway driving test is generally regarded as a gold standard for assessing drug-induced driving impairment. The primary outcome measure is the standard deviation of lateral position (SDLP), a measure of road tracking error or "weaving". The test has been calibrated for incremental doses of alcohol almost 30 years ago in order to define the impact of drug-induced impairment in terms of blood alcohol concentration (BAC) equivalents. Drug-induced changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant ever since. The present analysis was conducted to assess the robustness of the alcohol effect in a range of on-the-road driving studies which have been conducted since the initial alcohol calibration study. METHODS: The present study pooled data of 182 participants from nine placebo-controlled crossover studies who performed the highway driving test, while their BAC was at or just below the legal limit for drivers (i.e., 0.5 g/L). RESULTS: Overall, mean SDLP increased with 2.5 cm (95% CI 2.0-2.9 cm). Equivalence testing showed that the clinical relevance criterion value of 2.4 cm fell well within the 95% CI in each individual study. Gender did not affect alcohol-induced changes in SDLP. DISCUSSION: These results demonstrate the robustness and validity of the clinical relevance criterion for SDLP as measured during on-the-road driving.

On-the-road driving performance after use of the antihistamines mequitazine and l-mequitazine, alone and with alcohol.

OBJECTIVE: Previous studies demonstrated that mequitazine produces mild sedation after single doses. Its enantiomer, l-mequitazine, has a stronger potency for the H1 receptor. The aim of the current study was to assess the effects of l-mequitazine and mequitazine, alone and with alcohol, on driving. METHODS: Twenty-five healthy volunteers were treated with l-mequitazine 2.5, 5.0 and 10 mg, mequitazine 10 mg and placebo, alone and in combination with alcohol in a double-blind crossover design. Driving performance was assessed using the standardized highway driving test in normal traffic. Its primary measure is the Standard Deviation of the Lateral Position (SDLP). Secondary measures consisted of an auditory word learning test during driving, and subjective measures of driving performance. RESULTS: L-mequitazine 2.5 and 5.0 mg showed no effect on SDLP in the highway driving test, while SDLP significantly increased after l-mequitazine 10 mg (alone +1.59 cm; with alcohol +1.41 cm) and mequitazine 10 mg (with alcohol +1.17 cm). Alcohol significantly impaired all performance measures (SDLP +2.63 cm) but did not interact with the effects of treatment. Subjective measures indicated that participants were aware of the impairing effects of alcohol, but not of l-mequitazine and mequitazine. CONCLUSION: L-mequitazine can be considered safe to drive in dosages of 2.5 and 5.0 mg. L-mequitazine 10 mg led to mild driving impairment. Alcohol impaired all performance measures and added to the effects of l-mequitazine and mequitazine.