Dataset Information

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype.

ABSTRACT:

Introduction

Esmirtazapine is evaluated as a novel drug for treatment of insomnia.

Purpose

The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control.

Methods

Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine.

Results

Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected.

Conclusion

It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving.

SUBMITTER: Ramaekers JG

PROVIDER: S-EPMC3083504 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype.

Ramaekers Johannes G JG Conen Silke S de Kam Pieter Jan PJ Braat Sabine S Peeters Pierre P Theunissen Eef L EL Ivgy-May Neely N

Psychopharmacology 20110119 2

<h4>Introduction</h4>Esmirtazapine is evaluated as a novel drug for treatment of insomnia.<h4>Purpose</h4>The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control.<h4>Methods</h4>Treatments were administered in the evening. Driving performance was assessed in the morning ...[more]

PMID: 21246188

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Project description:Driving is increasing across the world and road traffic accidents are a major cause of serious injuries and fatalities. The link between alcohol consumption and impaired driving has long been established and has led to legislation in many countries, with enforcement of legal limits based on blood alcohol concentration levels. Alcohol hangover research is an emerging field with a range of laboratory and naturalistic studies now clearly demonstrating the significant impairments that can result from hangover, even when alcohol levels are measured at or close to zero the day following a social drinking occasion. Driving is a commonplace activity but requires competency with a range of complex and potentially demanding tasks. Driving impaired can have serious consequences, including death and serious injury. There have been only limited alcohol hangover driving studies. The studies presented examined the consequences of alcohol hangover with a driving simulator contrasting a group with zero residual alcohol (N = 26) next day and another with residual alcohol (N = 26) assessed with breathalyzer in the morning before undertaking a 20 min commute to work. All participants completed a morning drive after a night without alcohol consumption and another after a night of social drinking. The driving scenarios were relatively demanding including traffic and pedestrians, traffic lights and other potential hazards in a mixed rural and urban journey. Subjective hangover and workload were assessed in addition to a range of driving performance variables, including divided attention, steering control and driving violations. Analyses contrasted driving in the no alcohol condition with the residual alcohol condition. The combined groups data (N = 52) was contrasted with the zero and residual alcohol groups. Significant contrasts were found for a range of driving measures, including divided attention, vehicle control, and driving violations as well as perceived workload. The pattern of impairment was broadly similar across both groups, indicating that whether or not residual alcohol was present, consistent driving impairment was seen. The relatively high number of significant variables may reflect the increased cognitive demand of the 20 min commute drive including busy and complex urban environments. This was also reflected in the significant increase in perceived workload recorded across the 6 dimensions of the National Aeronautics and Space Administration Task Load Index (NASA-TLX). Associations between subjective measures and driving performance with hangover suggested a potential lack of awareness of impairment, though were limited in number. The overall findings indicate that the levels of impairment seen reflect those seen with alcohol impaired driving, even when breath alcohol is zero.

Dataset Information

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype.

Introduction

Purpose

Methods

Results

Conclusion

Publications

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype.

Similar Datasets

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