Effects of central nervous system depressant drug overdose on cognitive functions and driving

Self-poisoning with pharmaceutical agents is very common across the world. Central nervous system depressant drugs (CNS-Ds) are among the most common substances taken in overdose in hospital-treated episodes of self-poisoning in Australia, the UK and the US. The majority of the patients with CNS-D overdose treated in hospitals in Australia and the UK are discharged within 24-48 hours of their admission, when they still could potentially have subclinical effects of those drugs. This thesis systematically reviews published evidence on the effects of CNS-Ds on cognitive functions (Chapter 2), automobile driving and traffic accidents (Chapter 3, Paper 1), and presents original research conducted to examine the effects of CNS-D overdose on cognitive functions underpinning daily activities (Chapter 5, Paper 2), surrogate bedside tests of driving skills (Chapter 6, Paper 3) and risk of traffic accidents (Chapter 7, Paper 4) of patients discharged from hospital following treatment. Comprehensive neuropsychological assessment shows that patients discharged after treatment for CNS-D overdose have significant residual impairments in multiple cognitive functions including visual attention and visuomotor skills, decision-making, and executive functions and working memory (Chapter 5). The impairments, as estimated by regression models, were equivalent to a ‘cognitive ageing’ of 10-20 years depending on the domain tested. Furthermore, executive dysfunction of the patients tends to worsen with increasing task demands. Converging evidence from the neuropsychological assessment and epidemiological approach indicates that CNS-D overdose has deleterious effects on driving. In particular, the performance of Trail-Making Test B, when interpreted with respect to its correlation with driving performance and traffic accident risk, suggests that nearly two-thirds of the patients with CNS-D overdose may be grossly impaired (equal or less than 10th percentile) at the time of discharge from hospital (Chapter 6, Paper 3). The epidemiological evidence (Chapter 7, Paper 4) shows that the traffic accident risk of these individuals increases by 3-4 times in the immediate post-discharge period, and remains nearly twice their baseline risk after one week following overdose. In the concluding chapter (Chapter 8), we examine the impact of these impairments on daily activities that the discharged patients are expected and likely to carryout during the post-discharge period, and discuss the clinical implications in post-discharge management of patients treated for CNS-D overdose.