Kunihiro Iwamoto1, Mari Iwata2, Daiji Kambe3, Yumiko Imadera3, Naoki Tachibana3, Yu Kajiyama3, Masahiko Ando4, Norio Ozaki2. 1. Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan. iwamoto@med.nagoya-u.ac.jp. 2. Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan. 3. Taisho Pharmaceutical Co., Ltd, Tokyo, 170-8633, Japan. 4. Department of Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, 466-8560, Japan.
Abstract
RATIONALE: The effects of hypnotics on automobile driving have been attracting increasing attention. However, few driving simulators (DSs) have been confirmed to have acceptable reliability and validity for assessing the next-day residual effects of zopiclone as a positive control on driving performance. OBJECTIVE: To investigate whether a new DS could permit detection of the next-day residual effects of zopiclone on driving performance. METHODS: In this double-blind, randomized, placebo-controlled crossover trial, 28 healthy males received zopiclone 7.5 mg at bedtime on days 1 and 8 and placebo on the other days over a period of 16 days. The participants took part in three driving tasks-road-tracking, car-following, and harsh-braking-using a DS on days 2 and 9 at 9-h post-dosing. Scores on the Karolinska Sleepiness Scale and Profile of Mood States-Second Edition were then assessed, as was the serum concentration of zopiclone. RESULTS: The estimated differences in the standard deviation of lateral position (cm) in the road-tracking task between the zopiclone and placebo groups on days 2 and 9 were 3.75 cm (90% confidence interval (CI): 1.71-5.79) and 4.07 cm (90% CI: 2.02-6.11), respectively. The estimated differences in the distance coefficient of variation in the car-following task and in the brake reaction time in the harsh-braking task between the zopiclone and placebo groups on day 2 were 4.31 (90% CI: 1.94-6.69) and 24.6 ms (90% CI: 12.7-36.4), respectively. CONCLUSIONS: The DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance.
RATIONALE: The effects of hypnotics on automobile driving have been attracting increasing attention. However, few driving simulators (DSs) have been confirmed to have acceptable reliability and validity for assessing the next-day residual effects of zopiclone as a positive control on driving performance. OBJECTIVE: To investigate whether a new DS could permit detection of the next-day residual effects of zopiclone on driving performance. METHODS: In this double-blind, randomized, placebo-controlled crossover trial, 28 healthy males received zopiclone 7.5 mg at bedtime on days 1 and 8 and placebo on the other days over a period of 16 days. The participants took part in three driving tasks-road-tracking, car-following, and harsh-braking-using a DS on days 2 and 9 at 9-h post-dosing. Scores on the Karolinska Sleepiness Scale and Profile of Mood States-Second Edition were then assessed, as was the serum concentration of zopiclone. RESULTS: The estimated differences in the standard deviation of lateral position (cm) in the road-tracking task between the zopiclone and placebo groups on days 2 and 9 were 3.75 cm (90% confidence interval (CI): 1.71-5.79) and 4.07 cm (90% CI: 2.02-6.11), respectively. The estimated differences in the distance coefficient of variation in the car-following task and in the brake reaction time in the harsh-braking task between the zopiclone and placebo groups on day 2 were 4.31 (90% CI: 1.94-6.69) and 24.6 ms (90% CI: 12.7-36.4), respectively. CONCLUSIONS: The DS used in this study has sufficient sensitivity to detect the next-day residual effects of zopiclone on driving performance.
Keywords:
Driving performance; Driving simulator; Kunihiro Iwamoto and Mari Iwata joint first authorship and contributed equally to this paper; Positive control; SDLP; Sensitivity; Zopiclone