The influence of central nervous system depressant (CNS-D) drugs on driving performance and cognitive functions and recovery of cognitive functions following hospital treated deliberate self-poisoning (DSP) with CNS-D drugs

Hospital-treated deliberate self-poisoning (DSP) using central nervous system depressant drugs (CNS-D) has been shown to result in impairments to several cognitive and psychomotor functions important for daily activities such as driving. Our aim was to replicate previous findings that showed patients admitted to hospital following DSP with CNS-D drugs had cognitive and psychomotor impairments at discharge. The second aim was to examine recovery of impairments in the first month (day-7 and -28) for both a CNS-D and a central nervous system non-depressant (CNS-ND) drug group. The final aim was to examine the influence of prior, concurrent, and postDSP variables on recovery. The primary outcome measure, cognitive flexibility, replicated previous results: the CNS-D group were impaired at discharge compared with the CNS-ND group. CNS-D and CNS-ND groups did not significantly differ at discharge on other cognitive measures. Recovery of cognitive flexibility continued until day-28 in the CNS-D group whereas the CNS-ND group’s performance remained unchanged relative to discharge. Although not differing at discharge, working memory and cognitive efficiency showed slower recovery in the CNS-D than the CNS-ND group whereas recovery on other cognitive measures such as visual attention and inhibition was similar in both groups. More pre-DSP covariates influenced recovery in the first month after discharge such as age and intelligence, having a psychiatric diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder; and atypical antipsychotic medication. Patients discharged after DSP with CNS-D drugs have impaired cognitive and psychomotor functions which can require up to 1-month to recover. 54 The influence of central nervous system depressant (CNS-D) drugs on driving performance and cognitive functions and recovery of cognitive functions following hospital treated deliberate self-poisoning with CNS-D drugs. Chapter 2.Journal of Clinical Psychopharmacology Article Introduction Hospital-treated deliberate self-poisoning (DSP) has become a growing concern in developed countries as 90% (median; range 46.8-100%) of all deliberate self-harm is DSP. 1 DSP can be considered to be the consumption of two or more times the Defined Daily Dose (DDD) of the assumed average maintenance dose per day for a drug used for its main indication in adults with the intention of self-harm. Studies from developed countries show that central nervous depressant (CNS-D) drugs, such as benzodiazepines, newer non-benzodiazepine hypnotics, sedative antidepressants, atypical antipsychotics, and opioids are among the most commonly used drug groups in DSP. CNS-D drugs accounted for over 122,000 hospital treated DSP admissions in the US in 2008; 4 over 45,000 in the UK (mid 2010-2011); and over 12,500 in Australia (mid 20092010). At present, there has been limited research investigating the post-discharge impact of DSP with CNS-D drugs on cognitive and psychomotor functions that underpin daily activities, particularly demanding activities such as driving. One cross-sectional study has examined the cognitive and psychomotor functions at discharge of ambulant individuals admitted to hospital for DSP with CNS-D. In this study CNS-D drug overdose patients were compared with central nervous system non-depressant (CNS-ND) e.g. acetaminophen or non-sedating antidepressants, overdose patients across three domains of cognitive function (i.e., visual attention and visuomotor skills, executive functions and working memory, and impulsivity and decision making). The primary measures were Trail-Making Test-A (TMT-A) and Test–B (TMT-B), because of their ease of administration, usefulness in a clinical setting, and demonstrated relationship to driver performance (in both clinical and elderly populations). The CNS-D drug group performed poorly relative to the CNS-ND drug group across all domains of investigation. Differences in visual attention and visuomotor skills by the CNS-D group were demonstrated by significantly longer completion times for TMT-A and reaction times for a Choice 55 The influence of central nervous system depressant (CNS-D) drugs on driving performance and cognitive functions and recovery of cognitive functions following hospital treated deliberate self-poisoning with CNS-D drugs. Chapter 2.Journal of Clinical Psychopharmacology Article Reaction Time task (CRT). For tasks linked to executive functions and working memory, the CNSD group produced significantly longer TMT-B completion times, a significantly larger TMTB-A derived measure (TMT-B minus TMT-A completion times), recalled significantly less sets in the Letter Number Sequence task (LNS), and solved significantly fewer problems in the minimum number of moves for the Stockings of Cambridge Task from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Poor performance across all domains, in particular TMT-B, by participants in the CNS-D group suggested that DSP with CNS-D drugs reduces competence to perform tasks that require cognitive flexibility and attentional-switching. These results, and the noted relationship between TMT and driver performance raised questions about the discharge procedures of tertiary care facilities. Of particular concern is the longterm impact of a CNS-D drug DSP on patients daily functioning, in particular their capacity to drive, after being discharged. In response to these findings, Dassanayake, Jones, Michie et al. 12 conducted an epidemiological study designed to determine whether being discharged from hospital after DSP with psychoactive drugs produced an increased risk of a car accident. Data linkage between the New South Wales (NSW) Roads and Traffic Authority CrashLink database from 2001–2008 and the NSW Admitted Patient Data Collection was used to determine whether patients were at risk of a car accident within 3-days, 7-days and up to 1-month after ingestion of CNS-D drugs. Results showed that CNS-D individuals were 3.5 times at risk of a motor vehicle accident (MVA) after discharge, 1.9 times 7-days after discharge, and, surprisingly, 1.6 times 4-weeks after discharge compared to control periods of no hospital treatment for DSP. While the findings from the first week post-discharge suggest an ongoing impairment of cognitive and psychomotor function, it is less clear why individuals who ingest CNS-D drugs are at increased risk of being involved in a car accident up to 4-weeks after ingestion. Given the risk of 56 The influence of central nervous system depressant (CNS-D) drugs on driving performance and cognitive functions and recovery of cognitive functions following hospital treated deliberate self-poisoning with CNS-D drugs. Chapter 2.Journal of Clinical Psychopharmacology Article safety to the individual, and to the wider community, it is important to investigate possible explanations of these results. Psychosocial factors could explain the elevated risk of MVA up to 1-month after discharge; with those shown to influence driving performance including self-awareness, social maladjustment, vocational or financial concerns, 20 and psychopathology. Aims: 1. Compare the neurocognitive impairment (difference in means) at baseline (hospital discharge) for CNS-D and CNS-ND ingestion groups. 2. Compare the recovery of recovery of neurocognitive function (difference in means over time) over three time points (discharge, day-7, and day-28), for CNS-D and CNS-ND