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Biomedical subjects

I Hindmarch

Publications and source records attributed to I Hindmarch.

At least 55 records · Page 3Linked to original sources
PubMed1996

Comparison of the effects of astemizole/pseudoephedrine and triprolidine/pseudoephedrine on CNS activity and psychomotor function.

The sedative properties of astemizole-D and triprolidine-D were compared in a double-blind, placebo-controlled, repeated-measures design study comprising three experimental treatments, each with a duration of 2 days (n = 12). Sedation was assessed by continuous electroencephalographic measurement (C-EEG), intermittent performance testing and subjective measures. C-EEG monitoring revealed that triprolidine-D produced significantly more daytime sedation and drowsiness than either astemizole-D or placebo (p < 0.05). Intermittent performance testing did not reveal consistent psychomotor deficits. There were no differences from placebo; the only significant findings showed that astemizole-D improved tracking accuracy at T + 65 h (p < 0.05) compared to baseline. Also, when scores were summed across all time points, astemizole-D improved scores significantly in contrast to triprolidine-D for the total scores (p < 0.05). It is concluded that, in contrast to triprolidine-D, astemizole-D does not produce daytime drowsiness or sedation.

Adult↗
PubMed1995

The use of anti-depressants and benzodiazepines in the perpetrators and victims of accidents.

The objective of this study was to determine whether there is a greater incidence of psychotropic drugs in the blood of those 'responsible' for an accident compared with those not 'responsible' for an accident. Blood samples were taken from people involved in accidents presenting at the accident and emergency departments of two teaching hospitals over a five-month period and analysed for the presence of alcohol, tricyclic anti-depressants (TCAs) and benzodiazepines (BZs). Details of the accident were used to produce a test group (accidents where a drug may have contributed) and a control group (accidents where the presence of a drug could not have been a factor). In total, 229 samples were collected. The only criterion for inclusion in the study was that the accident was of sufficient severity to merit the routine taking of a blood sample, in which case an additional amount was taken for the purposes of this investigation. In all, 63 samples (27.5%) were positive for at least one of alcohol, TCA or BZ. Of the accidents represented by these samples, 48 could have been caused by the presence of the drug (responsible group) and 15 could not (not responsible group). There was a significantly greater representation of TCAs and BZs in the blood taken from the responsible group compared with the not responsible group (P < 0.0045).

Accidents↗
PubMed1995

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.

Behavior↗
PubMed1995

The behavioural toxicity of the selective serotonin reuptake inhibitors.

The serotonin reuptake inhibitors (SSRIs) are generally better tolerated than the traditional tricyclic antidepressants (TCAs) in the treatment of major depression. In particular the SSRIs are relatively free from cognitive and psychomotor effects likely to cause behavioural toxicity. Behavioural toxicity is studied using a battery of psychometric assessments. This paper discusses the effects of the TCAs and SSRIs on two such assessments, choice reaction time (CRT) and critical flicker fusion threshold (CFFT). CRT measures psychomotor speed, and CFFT assesses the information processing capacity of the CNS. The behavioural toxicity associated with the traditional TCAs can lead to an increased accident risk, whereas the SSRIs are not associated with such effects. Clinically relevant differences in the behavioural toxicity of the SSRIs are highlighted.

Accidents, Traffic↗
PubMed1995

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.

Administration, Oral↗
PubMed1994

The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers.

Eighteen healthy volunteers received mizolastine 5 mg, 15 mg or 45 mg, terfenadine 60 mg, triprolidine 10 mg or placebo in a 6-way crossover, double blind study. Following each dose, subjects performed a series of tests of cognitive function and psychomotor performance at 1, 3, 5, 8 and 24 hours post-dose. The test battery included critical flicker fusion, choice reaction time, tracking, Stroop and Sternberg memory tests and assessment of subjective sedation. Sedative effects and a concomitant reduction in psychomotor and cognitive function were observed following triprolidine, terfenadine and the highest dose of mizolastine, 45 mg, e.g. triprolidine reduced CFF threshold by 1.5 Hz and increased reaction time by 50 ms, impairments comparable to those caused by blood alcohol concentrations of 50 mg%, the legal limit in many countries. Mizolastine 5 mg did not differ significantly from placebo and at 15 mg differed only at one test point at one time. It may be concluded that mizolastine (5 mg and 15 mg) is free from disruptive effects on cognitive function and psychomotor performance, in contrast to terfenadine 60 mg, triprolidine 10 mg and mizolastine 45 mg.

Adolescent↗
PubMed1994

Selective serotonin reuptake inhibitors: meta-analysis of discontinuation rates.

A meta-analysis was carried out of 42 published randomized controlled studies comparing the selective serotonin reuptake inhibitors (SSRIs) with the tricyclic antidepressants (TCAs) that measured discontinuation rates for side effects and lack of efficacy by treatment group in order to compare the discontinuation rates for side effects and lack of efficacy. These discontinuation rates were pooled to produce the main outcome measure. Seven studies were placebo controlled and the discontinuation rates in these studies were also pooled in a separate analysis. Significantly fewer patients receiving SSRIs discontinued treatment because of side effects (14.9%) compared with those receiving TCAs (19%) (p < 0.01). There was also a significant difference in discontinuation rates due to side effects in the placebo- and TCA-controlled studies analysed separately, SSRIs (19%) compared with TCAs (27%) (p < 0.01). In both analyses a similar proportion of patients discontinued for lack of efficacy on SSRIs and TCAs. There is a significant and clinically important advantage for the SSRIs compared with the TCAs in the acceptability of treatment measured by the number of discontinuations due to side effects reported in published studies. The risk-benefit calculation favours the SSRIs since there were similar levels of efficacy but more discontinuations with the TCAs. The selection of an antidepressant for first-line treatment requires critical evaluation of the full risk-benefit equation.

Antidepressive Agents, Tricyclic↗
PubMed1994

Relevant psychometric tests for antidepressants and anxiolytics.

Psychometric tests can provide a sensitive and objective measure of drug effects which are of relevance to the clinical situation. Two tests, critical flicker fusion threshold and choice reaction time, used alone or as a part of a battery of tests, have been shown to be useful in detecting differences between drugs in their effect on cognitive and psychomotor functions. They provide important information on the activity and safety of drugs as they are used in practice.

Anti-Anxiety Agents↗
PubMed1994

Instrumental assessment of psychomotor functions and the effects of psychotropic drugs.

The basic assumption underlying psychopharmacology is that the effects of psychoactive drugs can be assessed by measuring the changes produced on aspects of human behaviour and cognitive function. This review concentrates on 3 established psychometric tests that have been shown over a long period of time to be not only valid and reliable measures of aspects of behaviour relevant to the daily activities of patients taking such drugs but also appropriate indicators of any countertherapeutic effects or side effects of medication. Choice reaction time (CRT) is a reliable index of sedation directly related to accident risk situations at home, on the road or at work. Critical flicker fusion threshold (CFFT), a direct measure of the capacity for processing cognitive information, is an accurate measure of various aspects of mental illness and drug effects, and the continuous daytime EEG (c-EEG) is a truly objective measure of CNS activity on a continuous 24-h basis. The judicious use of CRT, CFFT, CFFT and c-EEG not only demonstrates the inherent potential of certain molecules to adversely affect the performance of certain daily activities but also helps identify the drugs with profiles of activity or side effects that are likely to be countertherapeutic.

Antipsychotic Agents↗
PubMed1993

Amnestic effects of triazolam and other hypnotics.

1. The effects of a number of hypnotics were compared to a range of results collected for triazolam on objective measures of CNS sedation (critical flicker fusion) and short-term memory function (memory scanning). 2. Assessments taken after the drugs had been administered but prior to the onset of sleep showed that in comparison to placebo most of the compounds were effective sedatives and this correlated highly (r = 0.734, p < 0.04) with amnestic effects found at the same time, suggesting that general CNS sedation is a major component of anterograde amnesia. 3. Residual effects assessed the morning after the hypnotics had been used showed a similar relationship (r = 0.896, p < 0.005). 4. The distribution of results indicates that 0.25 mg triazolam has an acute amnestic profile which is similar to other hypnotics, but possesses a distinct lack of residual effects.

Adolescent↗
PubMed1993

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.

Adult↗
PubMed1993

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.

Administration, Oral↗
PubMed1992

Correlation between doses of oxazepam and their effects on performance of a standardised test battery.

Ten different doses of oxazepam (ranging from 7.5 to 50 mg) or placebo were administered to a total of 28 female subjects in three separate studies. Subjects completed a battery of psychometric tests at 1 and 2 h postdose. The tests included critical flicker fusion, choice reaction time and a tracking task. Following separate analyses of variance, effect sizes (Cohen's d) were calculated for each dose at each dependent variable. These effect sizes were then correlated with the dose of drug administered, using regression analyses. It was found that the doses correlated highly with most of the psychometric variables determined, implying that the test battery is sensitive to drug effects.

Adult↗