Human Psychopharmacology

To assess the status of serotonergic neurotransmission in depressed females, the authors examined the excretion of free cortisol in 24 h urine both before and after administering 5 g L‐tryptophan (L‐TRP) orally. The depressed patients were classified according to the DSM‐III into minor, simple major and major depression with melancholia. We found a significant, enhacing effect for L‐TRP on urinary free cortisol (UFC) excretion. The absolute increments in UFC induced by L‐TRP were significantly higher in melancholic females as compared to minor and simple major depressives. We found no differences among the DSM‐III groups in the availability of L‐TRP to the brain, 9 h after L‐TRP administration.

Behavioural and psychological symptoms in patients with dementia are common, distressing and often difficult to manage. This review evaluates a range of drugs commonly used to manage these symptoms including antipsychotics, anticonvulsants, antidementia drugs and antidepressants.

The risks and benefits of individual treatments are discussed and the relatively poor evidence base and need for further research is highlighted. Copyright © 2006 John Wiley & Sons, Ltd.

The effects of two nights of treatment with the short‐acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi‐center, randomized, double‐blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0·25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0·25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose‐response effects were apparent. Triazolam 0·25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0·25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow‐wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0·25 mg) produced increases in total sleep time (˜25 min) and decreases in latency to persistent sleep at a dose of 0·25 mg. Copyright © 2000 John Wiley & Sons, Ltd.

Although there is ample evidence for a cognitive‐attentional benefit of the stimulant nicotine, the source of this benefit is not as well understood. One approach is to address what aspects of performance nicotine affects at a functional systems level. It is currently debated whether the benefits produced by nicotine are the effect of enhanced higher cognitive function or reflect an overall increase in general arousal. In order to address this question, the effects of nicotine on two simple eye movement tasks were studied: the saccade (S) and antisaccade (AS) tasks. Because the S and AS tasks utilize identical sensory stimuli (peripheral targets) and require identical motor responses (eye movements) but differ significantly in their cognitive demands, the use of these two tasks should enable a parsing of nicotine effects on cognitive versus sensory‐motor processes. In this study, the S and AS tasks were performed by two experimental groups, task naïve subjects and highly practised subjects. For the first group, that of the task naïve subjects, nicotine gum administration resulted in a decrease in AS errors. For the second group, that of two experienced subjects tested repeatedly over a 3 week period, nicotine also produced a significant decrease in AS task errors, as well as resulting in a significant decrease in AS response times. Neither task naïve nor experienced subjects showed any effects of nicotine on the S task. Examining the effects of nicotine on highly controlled and constrained tasks such as the S and AS task may provide another level of insight into the mechanisms underlying the beneficial cognitive effects of nicotine. Copyright © 2004 John Wiley & Sons, Ltd.

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.

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.