Re: Stark MM, Wells D. Drug-mediated sexual assault.
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Comment↗
Biomedical subjects
I Hindmarch
Publications and source records attributed to I Hindmarch.
Abrupt and brief discontinuation of antidepressant treatment: effects on cognitive function and psychomotor performance.
The abrupt discontinuation of antidepressants can result in a syndrome of adverse events, including somatic, mood and psychomotor reactions. This study examined the effects of discontinuing and resuming antidepressant treatment with four selective serotonin reuptake inhibitors (SSRIs) on cognitive and psychomotor function. Eighty-seven patients receiving maintenance therapy with fluoxetine, sertraline, paroxetine or citalopram had their treatment interrupted for 4-7 days using double-blind placebo. Assessments of aspects of cognitive and psychomotor performance, mood and symptoms were carried out at each visit. Following interruption of treatment, significant differences between the groups emerged. Paroxetine treated patients experienced significantly more cognitive failures (P = 0.007), poorer quality of sleep (P = 0.016), and an increase in depressive symptoms, as rated both subjectively, using the Zung scale (P = 0.006) and by the clinician, using the Montgomery-Asberg Depression Rating Scale (P = 0.0003) and Clinical Global Impression (P = 0.0003), compared to some or all of the other drugs. All changes were reversed on reinstatement of treatment. Abrupt discontinuation of treatment with paroxetine leads to deterioration in various aspects of health and functioning, which may be related to the antidepressant discontinuation syndrome. These effects are not evident in patients receiving fluoxetine, sertraline and citalopram, suggesting they are not an SSRI class phenomenon.
Adult↗
Safety and tolerability considerations: tricyclic antidepressants vs. selective serotonin reuptake inhibitors.
OBJECTIVE: An important consideration in the choice of an antidepressant is its safety and tolerability. METHOD: We present a review of literature, clinical trials and meta-analyses regarding the safety and tolerability of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) in depressed patients. RESULTS: The SSRIs have a very favourable side-effect profile compared to the TCAs and are associated with fewer treatment discontinuations. Unlike the TCAs, they do not cause anticholinergic, hypotensive or sedating reactions, and are not associated with impaired cognitive function. Their most common side-effects (nausea, vomiting, nervousness, insomnia, headache and sexual dysfunction) are usually mild and typically disappear as treatment continues. The SSRIs also exhibit lower toxicity and lower lethality when taken in an overdose situation. Although the safety profiles of the principal SSRIs appear to be comparable, there is some data showing important differences in the severity and frequency of specific adverse events. CONCLUSION: The SSRIs have a more favourable safety profile than the TCAs in both acute and long-term treatment of major depression.
Antidepressive Agents, Tricyclic↗
The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers.
This study investigated the effects of acute doses of Ginkgo biloba extract (GBE) on memory and psychomotor performance in a randomized, double-blind and placebo controlled 5-way cross-over design. Thirty-one volunteers aged 30-59 years received GBE 150 mg (50 mg t. d.s), GBE 300 mg (100 mg t.d.s.), GBE 120 mg mane and GBE 240 mg mane and placebo for 2 days. Following baseline measures, the medication was administered at 0900 h for the single doses and at 0900, 1500 and 2100 h for the multiple doses. The psychometric test battery was administered pre-dose (0830 h) and then at frequent intervals until 11 h post dose. The results confirm that the effects of GBE extract on aspects of cognition in asymptomatic volunteers are more pronounced for memory, particularly working memory. They also show that these effects may be dose dependent though not in a linear dose related manner, and that GBE 120 mg produces the most evident effects of the doses examined. Additionally, the results suggest that the cognitive enhancing effects of GBE are more likely to be apparent in individuals aged 50-59 years.
Adult↗
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.
Adult↗
Antihistamines: models to assess sedative properties, assessment of sedation, safety and other side-effects.
Behavioural changes are produced by any drug that enters the central nervous system. These psychoactive effects include changes in alertness, concentration, attention, memory, cognition, psychomotor accuracy, skilled performance and affect. Changes in psychological performance may affect the safety of both the individuals taking the drug and of those people coming into contact with them. The aims of psychopharmacological performance tests are to describe the nature, extent and severity of these changes and identify drugs without deleterious effects upon performance. Use of traditional antihistamines has until recently been associated with a number of undesirable side-effects, the most troublesome of which is sedation. There are two aspects to sedation. Firstly, an objectively determined one based on the results of psychometric tests from controlled trials and secondly, the subjects response to the administration of a drug. Although the second generation of antihistamines have a much more favourable therapeutic index, use of these agents has also been reported to cause varying degrees of sedation. As antihistamines are largely used by ambulant patients, a complete evaluation of sedation should be performed through standardized objective tests, shown to be sensitive to the central effects of antihistamines as well as reliable ratings of subjective experiences. An extensive review of the literature has identified a number of tests which appear to be sensitive to the central effects of antihistamines. These include tests of psychomotor performance, sensori-motor co-ordination speed, information processing, sensory skills as well as physiological measures and subjective rating scales. Using this battery of cognitive and psychomotor tests, it is evident that only a very limited number of antihistamines can claim to be virtually free of both objective and subjective sedative effects, although the second generation of antihistamines are generally less impairing than the original ones; when prescribed at their recommended doses.
Cognition↗
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).
Adult↗
Summary of the conclusions
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Journal Article↗
Antihistamines: back to the future. Summary of the conclusions. BSACI. British Society for Allergy and Clinical Immunology.
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Animals↗
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.
Adult↗
The effects of black tea and other beverages on aspects of cognition and psychomotor performance.
Nineteen healthy volunteers ingested 400 ml black tea, coffee, caffeinated water, decaffeinated tea or plain water on three occasions through the day (0900, 1400 and 1900 hours). A 2 x 2 factorial design with caffeine (0, 100 mg) and beverage type (water, tea) was employed, with coffee (100 mg caffeine) as a positive internal control, based on a five-way crossover. A psychometric test battery comprising critical flicker fusion (CFF), choice reaction time (CRT), short-term memory (STM) and subjective sedation (LARS) was performed at regular intervals throughout the day, and intensively so immediately following each beverage. Consumption of tea compared to water was associated with transient improvements in performance (CFF) within 10 min of ingestion and was not affected by the time of day. Caffeine ingestion was associated with a rapid (10 min) and persistent reduction in subjective sedation values (LARS), again independent of time of day, but did not acutely alter CFF threshold. Over the whole day, consumption of tea rather than water, and of caffeinated compared to decaffeinated beverages, largely prevented the steady decline in alertness (LARS) and cognitive capacity observed with water ingestion. The effects of tea and coffee were similar on all measures, except that tea consumption was associated with less variation in CFF over the whole day. No significant treatment effects were apparent in the data for the STM. Tea ingestion is associated with rapid increases in alertness and information processing capacity and tea drinking throughout the day largely prevents the diurnal pattern of performance decrements found with the placebo (no caffeine) condition. It appears that the effects of tea and coffee were not entirely due to caffeine per se; other factors either intrinsic to the beverage (e.g. sensory attributes or the presence of other biologically active substances) or of a psychological nature (e.g. expectancy) are likely to play a significant role in mediating the responses observed in this study.
Adult↗
Cognition and anxiety: the cognitive effects of anti-anxiety medication.
There does not appear to be a single hypothesis or theory which can adequately explain the aetiology of anxiety, although there is no short-age of contenders. Neurochemical, existential, sociogenic, familial, pathological, psychodynamic and behavioural explanations have all been offered as putative reasons for the psychological disorder, which in its various representations (panic disorder, obsessive-compulsive disorder, phobias, post-traumatic stress disorder, generalized anxiety disorders, etc.) can affect up to 20% of the population on a lifetime basis (1). Notwithstanding the variety of theories and the diversity of presentation of anxiety disorders, it would appear that cognitive dysfunction of one sort or another is a characteristic feature of anxiety in all its manifestations. Indeed, it is possible to argue that a cognitive impairment is the primary presenting feature of pathological anxiety, with the characteristic syndrome of somatic symptoms as secondary or necessary consequences of such cognitive disorder.
Anti-Anxiety Agents↗
The Bayer Activities of Daily Living Scale (B-ADL).
The Bayer Activities of Daily Living Scale (B-ADL) has been developed on an international basis to assess deficits in the performance of everyday activities. The scale's main target group is community dwelling patients who suffer mild cognitive impairment or mild-to-moderate dementia. It comprises 25 items and takes the form of a questionnaire to be completed by a caregiver or other informant sufficiently familiar with the patient. Statistical, clinical and domain-related criteria were used to select items from among a large number of activities of daily living (ADL) questions field tested in pilot studies in the USA, Germany, UK, Russia and Greece. The items included in the B-ADL have been chosen for their sensitivity to cognitive impairment, simplicity of concept, international applicability and their relevance to patients coping with the demands of everyday life. The scale uses items which reflect a wide range of domains. On account of its brevity, it is thought especially suitable for application within a GP and primary care context for both screening a patient's ADL capacities as well as for documentation of treatment effects and the progress of dementia. This paper focuses on a description of the scale and its application.
Activities of Daily Living↗
The behavioural toxicity of antidepressants: effects on cognition and sexual function.
The cognitive system is structured from sets of schema, patterns of neural activity that allow the assimilation or accommodation of new experiences and so, by a process of consolidation, the gradual development of knowledge and understanding. As well as schema for purely cognitive processes, there are similar structures that enable individuals to deal with sexual behaviour and affectual relationships (e.g. hedonia, self-esteem, personal preferences and body image). In depression, there is a well established disruption of cognitive function that results in anhedonia and a loss of pleasure, including that from sexual activities. Many antidepressants also have a direct pharmacological action on the central nervous system and disrupt cognitive function, so increasing anhedonia and impairing sexual function. Drug actions on cognitive structures, which in turn increase anhedonia and reduce sexual libido, are over and above any direct pharmacological effects on the more overt behavioural activities associated with sex, including orgasm, erectile function, potency and ejaculation. The tricyclic antidepressants, for example, destroy the cognitive structures that are vital to maintain normal libido as well as disturbing overt sexual behaviours. Some selective serotonin reuptake inhibitors (SSRIs; paroxetine and sertraline) are associated with behavioural activation that is also responsible for an impairment of sexual function. However, there are clear differences between the SSRIs, and fluvoxamine (relative to the other SSRIs) has little effect on objective measures of cognition or on cerebral and behavioural components of sexual function.
Antidepressive Agents↗
The effects of antidepressants on psychomotor function with particular reference to reboxetine.
This review assesses the relative efficacy and side-effect profile of the currently available treatment options for major depression and the new selective noradrenergic agent, reboxetine. The effects of these treatments on psychomotor function are reviewed using: choice reaction time (CRT) and critical flicker fusion threshold (CFFT) measurements to compare and contrast the various antidepressants. Tricyclic antidepressant (TCA) agents are associated with an increased risk of accidents, especially in the elderly (primarily accidents related to driving or falls/fractures due to postural hypotension). In comparison, the newer noradrenergic agents such as reboxetine have demonstrated significant improvements in the incidence and severity of effects on psychomotor function. Such a lack of side-effects makes agents like reboxetine most useful for the treatment of depression in ambulant patients performing their usual activities of daily living.
Adrenergic Uptake Inhibitors↗
Evidence of the cross-cultural stability of the factor structure of the SKT short test for assessing deficits of memory and attention.
Many of the psychometric instruments employed in dementia research are adapted versions of tests developed in countries different from those in which they are applied. The validity of these instruments has been established in their countries of origin; however, there is little information available regarding their validity when transferred to other cultures. The SKT, a short cognitive performance test for the assessment of memory and attention deficits developed and validated in Germany, was administered in research centers in Chile, Greece, Russia, and England. SKT raw scores were factor analyzed with regard to a prespecified target structure, i.e., the factor solution found for a large German reference sample. The cross-cultural stability of the test was assessed using a statistical method that combined the perfect congruent weights approach and the bootstrapping technique. This procedure allowed for testing the similarity between factorial solutions obtained for the different centers. Results clearly indicate the factorial stability of the SKT in the countries participating in the study.
Adolescent↗
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.
Adult↗
The effects of reboxetine and amitriptyline, with and without alcohol on cognitive function and psychomotor performance.
Reboxetine is a novel antidepressant that has been shown to be effective in the treatment of major depressive disorders. The present experiment was designed to assess whether it affects the cognitive and psychomotor skills necessary for optimum function in everyday life. Ten healthy male volunteers received reboxetine 0.5 mg, 1 mg or 4 mg, amitriptyline 25 mg, or matched placebo with and without alcohol (0.6 mg kg-1) in a double-blind 10-way crossover study. A psychometric test battery was administered at baseline and at 1, 2.25, 3.5, 6 and 9 h post-dose. The results showed that reboxetine had little or no effect on performance at any dose, compared with placebo. Amitriptyline, however, with and without alcohol, lowered critical flicker fusion threshold compared with placebo and/or reboxetine at all test points (e.g. at 3.5 h: 28.51 vs 30.33 Hz; P < 0.05); increased reaction time (e.g. 619 vs 540 ms; P < 0.05); increased tracking error (e.g. 16.34 vs 8.54 RMS units; P < 0.05); and slowed short-term memory scanning (e.g. 742 vs 590 ms; P < 0.05). It is concluded that reboxetine at doses of 4 mg and below is free from disruptive effects on cognitive function and psychomotor performance, and that it does not act synergistically with alcohol, in contrast to amitriptyline.
Adolescent↗