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Residual effects of zopiclone on driving performance using a standardized driving simulator among healthy volunteers

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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.

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Funding

This trial was supported by Taisho Pharmaceutical Company, Ltd.; Research on Regulatory Science of Pharmaceuticals and Medical Devices from the Japan Agency for Medical Research and Development (JP21mk0101137h0003); research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Ministry of Health, Labour and Welfare of Japan; and a Grant-in-Aid from the “Center of Innovation for Personalized and Diverse Society” carried out under the Center of Innovation Program from the Japan Science and Technology Agency.

Research on Regulatory Science of Pharmaceuticals and Medical Devices from the Japan Agency for Medical Research and Development,JP21mk0101137h0003,Kunihiro Iwamoto,Ministry of Education,Culture,Sports,Science and Technology of Japan,Ministry of Health,Labour and Welfare,Grant-in-Aid from the “Center of Innovation for Personalized and Diverse Society” carried out under the Center of Innovation Program from the Japan Science and Technology Agency

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Authors and Affiliations

  1. Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan

    Kunihiro Iwamoto, Mari Iwata & Norio Ozaki

  2. Taisho Pharmaceutical Co., Ltd, Tokyo, 170-8633, Japan

    Daiji Kambe, Yumiko Imadera, Naoki Tachibana & Yu Kajiyama

  3. Department of Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, 466-8560, Japan

    Masahiko Ando

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  1. Kunihiro Iwamoto
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Correspondence to Kunihiro Iwamoto.

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Conflict of interest

KI has received speakers’ honoraria from Eisai, Kyowa, Meiji Seika Pharma, Otsuka, Sumitomo Dainippon, Taisho, Takeda, and Towa. MI has no conflicts of interest to declare. DK, YI, KN, and YK are employees of Taisho Pharmaceutical Co., Ltd., Japan. MA has received subsidies from Kyowa Kirin. NO has received research support or speakers’ honoraria from, or has served as a consultant to, Sumitomo Dainippon, Eisai, Otsuka, KAITEKI, Mitsubishi Tanabe, Shionogi, Eli Lilly, Mochida, DAIICHI SANKYO, Nihon Medi-Physics, Takeda, Meiji Seika Pharma, EA Pharma, Pfizer, MSD, Lundbeck Japan, Taisho Pharma, Janssen, UCB, Shionogi, Nihon Medi-Physics, Tsumura, Novartis, and Astellas.

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Iwamoto, K., Iwata, M., Kambe, D. et al. Residual effects of zopiclone on driving performance using a standardized driving simulator among healthy volunteers. Psychopharmacology 239, 841–850 (2022). https://doi.org/10.1007/s00213-022-06075-y

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