D. B. Fairweather

The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers

SummaryWe gave 24 healthy elderly volunteers with a perceived sleep onset of at least 30 minutes zolpidem 5 mg, zolpidem 10 mg, or placebo for 7 days in a double-blind, three-way, crossover study.The morning after nocturnal dosing, psychomotor performance and cognitive ability were measured using tests which are sensitive to the residual effects of hypnotics and to the effects of drugs on various indicators of sleep quality. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Word Recognition; the Leeds Sleep Evaluation Questionnaire and Line Analogue Rating Scales.Zolpidem produced a subjective improvement in sleep but did not impair performance the following day. Furthermore, during repeated administration, there was no tolerance to the effects of sleep latency and quality of sleep, nor adverse effects on task performance.

The effects of cigarette smoking on overnight performance.

Abstract Fifteen healthy smokers and 15 non-smokers were enrolled into this study investigating the effects of smoking on overnight performance. Subjects arrived at the test centre at 1930 hours and were assessed at baseline (2000 hours) and at 2200, 0000, 0200, 0400, 0600, and 0800 hours on a battery of tests (including Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Compensatory Tracking Task, CTT; Short Term Memory Task, STM; and the Line Analogue Rating Scale, LARS). Results showed that the performance of the smokers was more consistent with baseline measures than that of the non-smokers, which became more impaired throughout the night on a number of tasks [CFF (P < 0.005), Total Reaction Time (TRT, P < 0.05), CTT (P < 0.05) and the Reaction Time (RT) aspect of the CTT task (P < 0.0005)]. The Recognition Reaction Time (RRT) aspect of the CRT task showed that the performance of the non-smokers became more impaired from baseline (P < 0.005), while that of the smokers remained at baseline levels until 0400 hours, when it deteriorated to become comparable to that of the non-smoking controls. Subjective sedation ratings (LARS) resulted in comparable levels of impairment for both study groups (P < 0.00005). Findings from the STM task failed to reach significance. These data suggest that when performance is being measured overnight, smokers show little or no impairment, whilst the performance of non-smokers showed performance decrements.

Effects of fluoxetine and dothiepin on 24-hour activity in depressed patients

Psychomotor retardation is a recognised symptom of depressive illness, and improvement in psychomotor function is associated with the amelioration of the severity of depressive symptoms. Actigraphy permits behavioural activity to be continuously assessed, allowing changes in psychomotor activity to be monitored over time. A randomised, parallel-group, double-blind study was conducted in 14 general practice patients with a diagnosis of major depression. This pilot study was designed to investigate the utility of actigraphy in this patient population and to investigate possible differences between fluoxetine and dothiepin in their effects on 24-hour behavioural activity monitored for the first 10 days of treatment. Patients taking dothiepin (75 mg rising to 150 mg in the second week, nocte) were found to be significantly (p < 0.05) less active over the course of the day compared to those treated with fluoxetine (20 mg, mane). This lower level of behavioural activity in the dothiepin group was particularly noticeable in the early morning (06:00–08:00 h).

CITALOPRAM COMPARED TO DOTHIEPIN AND PLACEBO : EFFECTS ON COGNITIVE FUNCTION AND PSYCHOMOTOR PERFORMANCE

Three doses of citalopram (10, 20 and 40 mg), and placebo were administered to healthy volunteers for periods of 8 days each. Dothiepin 75 mg was given as an acute dose on days 1 and 8 only, with placebo dothiepin on days 2–7. Subjects were tested on days 1 and 8 of the dosing periods on a battery of psychometric tests. The results showed that citalopram at all doses had no detrimental effects on psychomotor performance. The effect of citalopram on critical flicker fusion (CFF) was to raise thresholds. This indicates an improvement in CNS function, i.e. an elevation of cognitive processing ability, with no evidence of an arousing or alerting effect. The effects were apparent after both acute and sub‐chronic dosing. These data are in contrast to those collected for dothiepin, which showed significant impairment of cognitive and psychomotor function on most of the measures employed. The most frequent adverse events reported for citalopram were drowsiness, nausea and headache, with the nausea appearing to be dose dependent. The main adverse events reported for dothiepin were drowsiness, sleepiness and dizziness. The rates of adverse events for all active treatments were not statistically significantly different to placebo. It is concluded that citalopram is relatively free from behavioural toxicity and so represents a significant improvement over the older antidepressant agents such as dothiepin.

The effects of fluoxetine and dothiepin on cognitive function in depressed patients in general practice

The objective of this study was to assess whether there are any differences between fluoxetine and dothiepin on cognitive function of patients with major depression (DSMIII‐R). A randomized, double‐blind, parallel group design, 6 week trial in patients in general practice was employed where patients were randomly allocated to one of two treatment groups, i.e. fluoxetine 20 mg mane or dothiepin 75 mg nocte (increasing to 150 mg in the 2nd week). Eighty‐four depressed patients aged 18–70 (mean 43·8) years were admitted to the study. Cognitive function was assessed by a valid battery of tests before and during treatment. The severity of depression was assessed using the Hamilton Depression Rating Scale (HAMD) at the start and end of the study. Both treatments were similarly efficacious in reducing the HAMD and performance tended to improve with both drugs during treatment. There were significant differences between the drugs on the critical flicker fusion task where the fluoxetine group performed significantly better than the dothiepin group (p<0·05). The fluoxetine group also had better scores on a mental arithmetic task. No significant differences were observed in the adverse event profiles. The results of this study show that fluoxetine and dothiepin cannot be differentiated in terms of efficacy manifest by changes in the HAMD, but do possess different profiles of action on the battery of cognitive tests. Copyright

The behavioral toxicity of reversible inhibitors of monoamine oxidase A: laboratory and clinical investigations.

Measuring the effect of an antidepressant on performance tests of psychomotor ability and cognitive processing is important in order to obtain an objective assessment of its psychotropic activity. It is also essential to identify potential interference with everyday activities such as driving, operating machinery, and performing domestic tasks and to assess the extent to which central nervous system side effects may compound the cognitive and psychomotor impairment resulting from depressive illness. Older compounds such as amitriptyline impair performance on these tests, whereas the newer antidepressant moclobemide appears to have no effect. What remains to be clarified is whether these tests are predictive of the behavioral side effects that may occur in depressed patients.

The effects of acute and repeated doses of suriclone on subjective sleep, psychomotor performance and cognitive function in young and elderly volunteers

Summary— Suriclone is a new anxiolytic drug belonging to the family of cyclopyrrolones. The effects of acute and repeated doses of suriclone on subjective sleep, psychomotor performance and cognitive function were compared to those of placebo in young and elderly volunteers. Young volunteers randomly received suriclone 0.2 mg, 0.3 mg, 0.4 mg or placebo tid, and the elderly received suriclone 0.1 mg, 0.2 mg or placebo tid. After the first single dose and after a three‐day treatment, subjects completed at 1, 2, 4, 12 and 24 h after drug administration the following battery of psychomotor and cognitive tests: critical flicker fusion threshold, choice reaction time, simulated car tracking test, the stroop test and the Sternberg memory scanning task. Visual analogue scales and the Leeds sleep evaluation questionnaire were also administered during the study. No significant effects of suriclone compared to placebo were seen on the psychomotor tests both in young and elderly volunteers. The only significant result was an improvement of the ease of getting to sleep in the young with 0.4 mg suriclone tid. In conclusion, there is little evidence to suggest that suriclone produces any measurable behavioural toxicity, so often seen with many of the benzodiazepines, in either young or elderly subjects.

The Effect of Paroxetine and Dothiepin on Subjective Sleep in Depressed Patients

Paroxetine improve the quality of sleep and the ease of waking up on subjective measures of sleep (the LSEQ). Dothiepin in contrast improved the ease of getting to sleep, but caused a reduced quality of sleep and a ‘hangover’ effect the next morning.

The Effects of Moclobemide on Psychomotor Performance and Cognitive Function in the Elderly

Behavioural toxicity is a side-effect of many psychoactive drugs and can be defined as the extent to which a centrally acting compound disrupts those abilities necessary for the performance of the psychomotor and cognitive tasks of everyday life. Moclobemide is a novel antidepressant which functions by the reversible inhibition of monoamine oxidase-A (MAO-A). In an elderly population moclobemide was shown to be no different from placebo in tests of psychomotor performance and cognitive function. As a reversible MAO inhibitor with a neutral profile of behavioural toxicity, this compound may make a valuable contribution to the treatment of depression in the elderly.

Evaluation of the efficacy of metaclazepam and its effects on sleep, psychomotor performance and cognitive function in anxious patients

The effects of single and multiple doses of metaclazepam were investigated in 60 anxious patients. A 15 mg nocturnal dose of metaclazepam was compared to two daily doses (5 mg in the morning and 10 mg at bedtime) in terms of efficacy and effects on various aspects of sleep, cognitive function and psychomotor performance. Anxiolytic efficacy was assessed by means of questionnaires, including the Self Rating Anxiety Scale of Zung, State Trait Anxiety Inventory of Spielberger, and a modified version of the Hamilton Anxiety Rating Scale. Hypnotic activity was evaluated using a clinical rating of insomnia questionnaire. The psychometric battery consisted of tests of Critical Flicker Fusion, Choice Reaction Time and Digit Span. In terms of clinical efficacy, metaclazepam administered in either dosage regimen demonstrated a good anxiolytic activity profile. Both dosage regimens were effective in improving the quality and quantity of sleep, however the number of intermittent awakenings were significantly higher with the daily divided dose. In addition, the nocturnal administration of metaclazepam did not appear to be associated with any undesirable side effects or decrements in psychomotor performance the following morning. In conclusion, it appears that a 15 mg bedtime dose of metaclazepam is efficacious in relieving anxiety without impairing psychomotor performance the following morning.