Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use

A. Vermeeren, E.F. Vuurman, T.R. Leufkens, C.J. Van Leeuwen, A.C. van Oers, E. Laska, S. Rico, F. Steinberg, T. Roth

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Abstract

STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.
Original languageEnglish
Pages (from-to)489-496
JournalSleep
Volume37
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Vermeeren, A. ; Vuurman, E.F. ; Leufkens, T.R. ; Van Leeuwen, C.J. ; van Oers, A.C. ; Laska, E. ; Rico, S. ; Steinberg, F. ; Roth, T. / Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. In: Sleep. 2014 ; Vol. 37, No. 3. pp. 489-496.
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title = "Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use",
abstract = "STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45{\%} of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.",
author = "A. Vermeeren and E.F. Vuurman and T.R. Leufkens and {Van Leeuwen}, C.J. and {van Oers}, A.C. and E. Laska and S. Rico and F. Steinberg and T. Roth",
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Vermeeren, A, Vuurman, EF, Leufkens, TR, Van Leeuwen, CJ, van Oers, AC, Laska, E, Rico, S, Steinberg, F & Roth, T 2014, 'Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use', Sleep, vol. 37, no. 3, pp. 489-496. https://doi.org/10.5665/sleep.3482

Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. / Vermeeren, A.; Vuurman, E.F.; Leufkens, T.R.; Van Leeuwen, C.J.; van Oers, A.C.; Laska, E.; Rico, S.; Steinberg, F.; Roth, T.

In: Sleep, Vol. 37, No. 3, 01.01.2014, p. 489-496.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use

AU - Vermeeren, A.

AU - Vuurman, E.F.

AU - Leufkens, T.R.

AU - Van Leeuwen, C.J.

AU - van Oers, A.C.

AU - Laska, E.

AU - Rico, S.

AU - Steinberg, F.

AU - Roth, T.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.

AB - STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.

U2 - 10.5665/sleep.3482

DO - 10.5665/sleep.3482

M3 - Article

VL - 37

SP - 489

EP - 496

JO - Sleep

JF - Sleep

SN - 0161-8105

IS - 3

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