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The Therapeutic Goods Act 1989 requires diazepam to be labelled with the caution “This medication may cause drowsiness and may increase the effects of alcohol. If affected do not drive a motor vehicle or operate machinery” (Department of Health and Ageing 2009). The usefulness of the information conveyed on this label in reducing crash risk is reliant on an individual’s ability to perceive the sedative effects. Furthermore, it is reliant on the assumption that psychomotor impairment occurs only in the presence of subjective sedation or drowsiness. There are no known studies to date that have been conducted with the aim of providing evidence for or against this notion. A method for approximating the reliability of psychomotor impairment only occuring in the presence of subjective sedation would be to examine patterns of results in the literature and look for dissociations between the objective performance and subjective sedation measures. It could be expected that if psychomotor impairment did only occur in the presence of subjective sedation when under the influence of diazepam, subjective sedation measures would increase and decrease alongside objective performance measures (i.e. there would not be a dissociation between these measures).

Benzodiazepine studies that allow for a comparison between subjective sedation ratings and actual performance at similar time-points have yielded inconsistent results. The results of some studies suggest a dissociation between subjective sedation and actual performance, with psychomotor performance being significantly affected whilst subjective sedation effects remain non-significant (e.g. Roache & Griffiths, 1985; C. Rush, Frey, & Griffiths, 1999; Tiplady, Bowness, Stien, &

Drummond, 2005). Other studies do not provide evidence for a dissociation with subjective sedation being significantly affected alongside actual performance (Allen, Curran, & Lader, 1993; Begg, et al., 2001; Farre, et al., 1996; Mintzer & Griffiths, 2003; Roache, et al., 1993; Verster, Volkerts, &

There are two known diazepam studies including subjective sedation measures that allow for the calculation of effect sizes, enabling a more precise examination of potential dissociations. In one of these studies there is a notable time-related pattern that is suggestive of a dissociation between subjective sedation and objective performance. Takahashi and colleagues (2010) found a 5mg dose to result in small to moderate deleterious effects on a series of objective measures (derived from a vigilance task and a driving simulator task) at 1 hour post-ingestion (with effect size changes from baseline (g) ranging from 0.19 to 0.51). These effects were slightly reduced in magnitude at 4 hours post-ingestion (with effect size changes from baseline (g) ranging from 0.10 to 0.35). Meanwhile effects on subjective sedation (as measured by the Subjective Sleepiness Scale) increased in magnitude across these time points, with effect size changes from baseline (g) of 0.85 at 1 hour post-ingestion, and 1.03 at 4 hours post-ingestion. It may well be that diurnal variations are involved in this dissociation between subjective sedation and objective performance effects. This however, does not change the implication of these results, in that there appears to be a dissociation between subjective sedation measures and actual performance measures in this study.

Patterns of effect sizes across two age groups in a study by Echizenya and colleagues (2007) are also indicative of a dissociation between subjective sedation and actual performance. In this study an older group of participants (53 to 71 years) and a younger group of participants (18 to 23 years) were administered a 5mg dose or placebo. In the older participants a deleterious effect on choice reaction time (CRT) performance was of a greater magnitude than that on subjective sedation (as measured by the Subjective Sleepiness Scale) with effect size changes from baseline (g) of 1.00 and 0.32 respectively. The opposite pattern was evident for the younger participants, with CRT effects being of a lower magnitude than subjective sedation effects (effect size changes from baseline (g) of 0.70 and 0.90 respectively). Age did not impact on subjective sedation in the same manner that it did on actual performance in this study, which is suggestive of a dissociation between these measures.

Further studies allow for a comparison of subjective sedation and actual performance under the influence of diazepam, however, effect sizes can not be calculated for these studies. A large number of these studies found subjective sedation measures to be significantly affected by diazepam along side objective performance measures (Brown, et al., 1996; Echizenya, et al., 2003; Kelland & Lewis, 1996; Mattila & Mattila, 1988; Rich, et al., 2006; Vanakoski, et al., 2000). Some studies, however, provide evidence for a dissociation between subjective sedation and actual performance. In two separate studies Mattila and colleagues (1988; 1998) found 15mg of diazepam to result in significantly poorer tracking performance and significantly slower psychomotor

processing speed, whilst subjective ratings of sedation remained non-significantly affected. Similarly, Hart and colleagues (1976) found that 5mg of diazepam resulted in significantly slower processing speed than 2.5mg of diazepam whilst differences between the subjective ratings of sedation for the two doses were non-significant. Deakin and colleagues (2004) also found significant dose-related (5mg, 10mg and 20mg) decrements in actual performance whilst dose-related effects on subjective sedation ratings were non-significant.

The dissociations between subjective sedation measures and actual performance measures

highlighted in the above studies are all indicative of diazepam affecting drowsiness and psychomotor performance in discrete ways. Subjective sedation effects do not necessarily increase and decrease alongside actual performance measures across time post-ingestion, across diazepam dose increases, or across age. Doses as low as 5mg and as high as 20mg have been shown to result in dissociated sedative and performance effects. These findings suggest that subjective sedation may not be a reliable predictor of actual psychomotor performance, and the potential for experiencing

psychomotor performance detriment in the absence of feeling drowsy remains a possibility. This raises questions about the usefulness of the information conveyed on current benzodiazepine labelling in reducing crash risk.

Equating diazepam-induced impairment to a blood-alcohol concentration