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.Keywords: antihistamines, cognitive function, fexofenadine, loratadine, promethazine, psychomotor performance the patient at an increased risk of accidents in situations Introduction such as driving and operation of machinery, where high levels of alertness are required [5][6][7], but also reduce Antihistamines are the drugs of choice in the symptomatic treatment of various allergic disorders such as seasonal compliance with treatment regimens due to excessive fatigue and malaise. and perennial allergic rhinitis and chronic urticaria [1, 2]. However, the use of traditional antihistamines such as Adverse effects experienced with older drugs with sedative effects resulted in the development of a second diphenhydramine, chlorpheniramine, triprolidine and promethazine is often associated with a number of generation of antihistamines with equipotent antiallergic action. Clinical trials have consistently demonstrated that unwanted side-effects of which sedation is the most pronounced [3][4][5]. These side-effects can interfere with the second generation antihistamines have a much more favourable therapeutic index and a significantly lower the performance of daytime activities and not only place incidence of sedative effects tha...

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.

Sixty-six elderly depressed patients received fluoxetine 20 mg (FLU) or amitriptyline 75 mg (AMI) for 42 days in a double blind parallel group study. Each week, subjects completed a test battery which is sensitive to the residual effects of psychoactive drugs. The results show that FLU and AM1 were equally effective in relieving depression. However, the psychometric test battery showed that, compared to FLU, AMI, as expected, produced impairments in cognitive function and psychomotor performance. The relative impairment of cognitive and psychomotor skills following the tricyclic AM1 and the lack of such activity after administration of the selective serotonin reuptake inhibition, FLU are important considerations when prescribing antidepressants, especially when the safety and well being of ambulant patients is essential.

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.

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).

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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. © 1997 by John Wiley & Sons, Ltd.

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