A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function.

AIMS: To assess whether fexofenadine in a range of doses from 80 to 180 mg has any disruptive effects on aspects of psychomotor and cognitive function in comparison with placebo, loratadine and promethazine, an antihistamine known to produce psychomotor and cognitive impairment. METHODS: Twenty-four healthy volunteers received fexofenadine 80 mg, 120 mg and 180 mg, loratadine 10 mg, promethazine 30 mg (as a positive internal control) and placebo in a six-way crossover, double-blind study. Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3, 6, 9, 12 and 24 h post dose. The test battery included critical flicker fusion (CFF), choice reaction time (CRT) and assessment of subjective sedation (LARS). Overall levels of activity were monitored by means of wrist mounted actigraphs throughout each of the 24 h experimental periods. RESULTS: Fexofenadine at all doses tested was not statistically different from placebo in any of the tests used and loratadine did not cause any significant impairment of cognitive function. Significant impairments were found following promethazine. Promethazine caused a significant reduction in CFF threshold and this effect was evident up to 12 h post dose (P<0.05). There was a significant increase in recognition reaction time at 3 and 6 h post promethazine administration, and the drug caused a significant (P<0. 002) increase in the percentage of 'sleep-like' activity from actigraph records during the daytime. CONCLUSIONS: Fexofenadine at doses up to 180 mg appears free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg.

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).

The effects of cigarette smoking on overnight performance.

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 fluvoxamine and dothiepin on psychomotor abilities in healthy volunteers.

We gave 12 healthy male volunteers single doses of 50 mg fluvoxamine, 100 mg fluvoxamine, 75 mg dothiepin, and placebo in a double-blind crossover study. Subjects completed a test battery that was sensitive to the behaviourally toxic effects of psychoactive drugs prior to dosing, and then at 1, 2, 3, 4, and 6 h after dose. The test battery included tasks of choice reaction time, tracking, critical flicker fusion threshold, and memory scanning. Subjective feelings were assessed using the line analogue rating scales and the Milford-Epworth sleepiness scale. Daytime activity was recorded by means of wrist actigraphy. The results show that the positive internal control (dothiepin) had a sedative effect in that it impaired performance in the majority of the tests and also reduced daytime activity. Both doses of fluvoxamine remained relatively neutral throughout and did not impair psychomotor performance or cognitive ability in any of the tests. These results indicate that fluvoxamine may be a safe and efficacious antidepressant for outpatients who wish to carry on with the tasks of everyday life without being sedated.

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 psychomotor and cognitive effects of litoxetine in young and middle aged volunteers.

1. The effects of a range of doses of litoxetine (twice daily for 4 days), a novel specific serotonin re-uptake inhibitor, were evaluated in young and middle aged volunteers. 2. Psychometric testing was carried out at various time points on days 1 and 4 of each treatment period. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT), Stroop and Sternberg memory scanning tests. Subjective feelings of sleep and sedation were measured by the Leeds Sleep Evaluation Questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic profiles were determined from analyses of blood samples taken after the final dose on day 5. 4. Overall, there were few changes in any of the psychometric tests and although the higher doses of litoxetine improved CFF, these effects were weak in that differences could only be detected when the results were pooled against time. 5. The pharmacokinetic profile of litoxetine was very similar in both the young and middle aged subjects, and there was no difference regarding tolerability. 6. There is little evidence from this study to suggest that litoxetine has any intrinsic sedative activity which is likely to interfere with the performance of activities of everyday life.

Assessing the residual effects of hypnotics.

The therapeutic efficacy of a hypnotic can not be judged solely on its ability to induce and improve sleep. Many of the older compounds produce residual effects the next morning, such as impaired performance, lack of concentration and day-time sedation. This "hangover" phenomena will only serve to make the problem worse rather than better. The patient's quality of life would suffer, and this is particularly apparent in older patients. Zopiclone and zolpidem, two novel compounds, are superior to the older benzodiazepines in that they do not impair performance on tests of cognition, reaction time and memory the day following drug ingestion. These drugs may prove to be more beneficial and safer in people with sleep disorders who want to carry on with everyday life.

A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers.

1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout.

The effects of moclobemide on psychomotor performance and cognitive function.

Sixteen young male volunteers received single doses of moclobemide 200 mg, moclobemide 400 mg, amitriptyline 50 mg and placebo in a double-blind crossover study. Subjects then completed a test battery which is sensitive to the effects of psychoactive drugs at 1, 2, and 4 h post-dose. The test battery included tasks of choice reaction time, tracking, critical flicker fusion threshold and memory scanning. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). The results show that the positive internal control (amitriptyline) has a sedative effect in that it increased critical flicker fusion threshold, reaction time and tracking error. Moclobemide 400 mg increased reaction time in the tracking task but neither dose of moclobemide impaired psychomotor performance or cognitive ability in any of the other tests.

The effects of paroxetine, alone and in combination with alcohol on psychomotor performance and cognitive function in the elderly.

Fifteen healthy male volunteers aged over 60 years received acute and repeated doses of paroxetine 20 mg or placebo, and acute doses of lorazepam 1 mg (as a positive internal control) with or without alcohol (0.6 g/kg of body weight) administered openly in a double blind balanced crossover study in which each subject acted as his own control. Psychomotor performance and cognitive function were assessed using a test battery which included critical flicker fusion, choice reaction time, compensatory tracking, Stroop and memory scanning tests. Subjective ratings of mood and sleep were recorded using line analogue rating scales. The pattern of results indicated that paroxetine had little or no effect on most of the test variables, and in some instances (critical flicker fusion thresholds) improved information processing ability. This was in marked contrast to the lorazepam verum which produced sedation and disruption of performance. Paroxetine had a slight antagonistic effect on alcohol induced sedation whereas impairment of performance with lorazepam was potentiated by co-administration of alcohol. The low behavioural toxicity of paroxetine in elderly volunteers has important implications for the pharmacotherapy of depression.

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

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

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.