Human Psychopharmacology

The present study was conducted to determine the degree to which impairments in attention accompany the memory deficits produced by scopolamine. Eighteen healthy young volunteers received scopolamine 0·6 mg subcutaneously on three experimental sessions and placebo on three others. On each session, prior to, and 60 min after injection, the subjects underwent an automated computerized battery of 11 cognitive tasks. The study was run double‐blind and the order of treatment conditions over successive visits was counterbalanced between subjects. Scopolamine produced marked and significant decrements on all major aspects of performance from the battery. The drug lowered the efficiency of the detection and processing of information in tests of visual vigilance, rapid information processing, choice reaction, letter cancellation and logical reasoning. These effects were accompanied by a lowering of critical flicker‐fusion frequency and subjective alertness. Memory was also impaired on tests of immediate recall, delayed recall, recognition and memory scanning. These findings confirm and extend previous work, demonstrating that scopolamine impairs the selection and evaluation of environmental information, as well as reducing the likelihood of information being subsequently recalled or recognized. Whether the former effects contribute to the latter is not known, but this must be considered a possibility. This potential role of processing deficits in memory loss associated with cholinergic blockade is briefly considered in relation to the cholinergic hypothesis of geriatric memory loss.

While there is no doubt that benzodiazepine administration leads to transient cognitive impairment in healthy adults, the nature and magnitude of such impairment has not been well described. The cognitive effects of a single dose of alprazolam 0.5 and 1 mg were therefore assessed in 36 healthy adults on measures of psychomotor function, visual attention, working memory, planning and learning in a double‐blind parallel‐groups study. Measures of these different cognitive functions were selected on the basis of their brevity and because they yielded distributions of performance data that were without skew, floor or ceiling effects of range restriction (i.e. normal distributions). With data satisfying the assumptions for parametric analysis, measures of effect size could be computed in addition to significance testing, thus allowing for direct and meaningful comparison between the different performance measures used. Alprazolam 0.5 mg reduced only the speed of attentional performance although the magnitude of this reduction was large (d = 0.8). At 1.0 mg, impairments in psychomotor function, equivalent to that seen for attentional function at the lower dose, were observed. In addition, moderate (d approx = 0.5) impairments in working memory, and learning also became obvious. When considered together, these results suggest that low‐dose alprazolam primarily alters visual attentional function. At the higher dose psychomotor functions also become impaired, and it is likely that the combination of these led to the observed moderate impairments in higher level executive and memory processes. The current study also illustrates a method for directly comparing the magnitude of change in cognitive function between measures with different performance metrics. Copyright © 2005 John Wiley & Sons, Ltd.

Twenty‐two Korean inpatients with delirium were administered prospectively a flexible dose of quetiapine. The delirium rating scale‐revised‐severity 98 (DRS‐R‐98) and clinical global impression scale‐severity (CGI‐s) scores were assessed at the time of pre‐ and post‐treatment. The DRS‐R‐98 and CGI‐s scores were significantly reduced by 57.3% and 55.1%, respectively. Quetiapine was effective and safe for the treatment of patients with delirium, and could be a useful alternative agent to classical antipsychotics in the treatment of delirium. Copyright © 2004 John Wiley & Sons, Ltd.

The main purpose of this study was to compare the sensitivity of a driving simulator test model (TS2) with a standard on‐the‐road driving test, after one night treatment with lormetazepam 1 mg, oxazepam 50 mg (as a verum) and placebo. The secondary purpose was to measure the effects of the intended drugs and placebo in the same subject sample, after two treatment nights in the morning and in the afternoon, on on‐the‐road driving performance. Eighteen healthy male volunteers received the three treatments (2 consecutive nights each) according to a double‐blind, three‐way crossover design. Time of administration was set at 22.00 hours each night. An on‐the‐road driving test and a simulator driving test were conducted in the morning following the first night. After the second treatment night, on‐the‐road driving tests were performed in the morning and in the afternoon. The on‐the‐road driving test consisted of operating an instrumental automobile over a 100 km highway circuit at a constant speed (90 km/h) and constant steady lateral position between the right lane boundaries. Primary performance measure was the SD of lateral position (SDLP). The simulator test consisted of repeatedly performing ‘curve‐following’ manoeuvres, which was the main tracking control task, while simultaneously reacting to secondary visual signs. Test parameters were the number of correctly executed manoeuvres (TC) and reaction time (RT). Oxazepam 50 mg seriously impaired, and lormetazepam 1 mg slightly impaired, on‐the‐road driving performance in the morning, both after the first and second treatment night. The drugs produced no significant effects in the afternoon test following the second night. In contrast with these results, neither oxazepam 50 mg nor lormetazepam 1 mg affected simulator tracking control after one night. No deterioration was found for reaction time. Correlational and multiple regression analyses were applied to determine relationships between SDLP, TC and RT. The major conclusion of this study was that the TS2 driving simulator test does not predict residual drug effects in the on‐the‐road driving test, and seems to be a less sensitive measure of sedative drug‐induced impairment in contrast to the on‐the‐road driving test.

The use of cognitive tests as measures of treatment response in individual children with ADHD has not been adequately evaluated or commonly applied by clinicians. This is most likely due to a lack of suitable assessment tasks as well as clinicians' limited awareness of the appropriate statistical techniques for analysing cognitive change in individuals. This study investigated the application of statistical decision rules to the cognitive and behavioural measures of individual children with ADHD in order to classify a significant, positive response to medication. The previously reported data of 14 children with ADHD (combined type; ADHD‐CT) were re‐analysed to investigate changes in function following a low‐ and high‐dose of stimulant medication (2.5 mg and 7.5 mg dexamphetamine, respectively). The performances of 14 age‐, gender‐ and IQ‐matched controls was also analysed to provide an estimate of the false‐positive classification rate. Overall, the decision rule yielded a high sensitivity and high specificity to treatment response. In the high‐dose condition, 71% of children with ADHD demonstrated improvements in both cognitive and behavioural function. This study demonstrates an evidence‐based approach to evaluating concurrent cognitive and behavioural improvement in individual children with ADHD following treatment with stimulant medication. Copyright © 2004 John Wiley & Sons, Ltd.