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Biomedical subjects

I Hindmarch

Publications and source records attributed to I Hindmarch.

At least 19 recordsLinked to original sources
PubMed2004

A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults.

One of the most popular herbal remedies for the alleviation of sleep problems is valerian. However, research into valerian is sparse, and studies differ greatly with respect to design, measures, and preparations used. This clinical study used standardized sleep EEG and psychometric tests to evaluate the clinical efficacy of a valerian preparation (Li 156). A placebo-controlled three way crossover clinical trial was completed using 16 (5 male and 11 female) sleep-disturbed participants (aged 50 to 64 years, mean age 55.9, SD 4.68). Participants slept overnight in a sleep laboratory, following a 21:00 hours dose of valerian 300 mg, valerian 600 mg, or placebo (double-blind). EEG sleep was recorded for each participant at 23:00 hours until 07:00 hours, when a psychometric evaluation was performed the morning after dose. Test periods were separated by six days washout period. Results showed no significant effect between valerian 300 mg, valerian 600 mg or placebo on any EEG parameter or psychometric measure. This suggests valerian at these doses is ineffective as an acute dose for sleep problems. However, valerian is widely used, and is traditionally sedative. Therefore, more research is required into therapeutic dose, types of valerian preparation, and the optimum period of use for therapeutic effect.

Aging↗
PubMed2004

Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study.

The effects of an abrupt interruption of agomelatine, a new melatonergic/serotonergic antidepressant, were explored in a double-blind, placebo-controlled study. Paroxetine was used as active control. After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day, sustained remitted depressed patients were randomized for 2 weeks, under double-blind conditions, to placebo or to their initial antidepressant treatment. Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms (DESS) checklist. One hundred and ninety-two sustained remitted patients were randomized to the 2-week discontinuation period. Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine. Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms, during the first week, compared to those who continued with paroxetine (respective mean number of emergent symptoms: 7.3+/-7.1 and 3.5+/-4.1, P<0.001). No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation. By contrast to paroxetine, abrupt cessation of agomelatine is not associated with discontinuation symptoms.

Acetamides↗
PubMed2003

A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performance.

OBJECTIVE: To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. METHOD: In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20mg mane, mirtazapine 15mg/30mg nocte (comparator), mirtazapine 15mg mane/15 mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included 'on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. RESULTS: Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15mg/30mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15mg mane/15mg b.i.d. improved sleep, but significantly impaired all other measures. CONCLUSION: Paroxetine 20 mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results.

Adrenergic alpha-Antagonists↗
PubMed2002

Beyond the monoamine hypothesis: mechanisms, molecules and methods.

The first effective antidepressants (monoamine oxidase inhibitors and tricyclic antidepressants) relied on their ability to augment serotonin and noradrenaline levels at the synapse. Forty years later, the same biological model led to the supremacy of the serotonergic hypothesis to explain not only the pathophysiology of depressive illness, but also the neuropharmacological basis for obsessive compulsive disorder, phobias, posttraumatic stress disorder, and even generalized anxiety disorder. It could be argued that the blinkered view of depression as a solely serotonergic phenomenon has not only restrained and limited research into other potential systems, but has also slowed down the discovery of putative antidepressant drugs. While some might argue that the hypothalamic-pituitary-adrenal (HPA) axis explains an individual's sensitivity to depression, there are others who equally claim that the most likely explanations are to be found in the neuropsychopharmacology of the immune system or even through reductions in hippocampal volume. There is a richness of possibilities regarding the mechanisms for antidepressant activity embracing theoretical, pharmacological and clinical data. However, the methods by which putative antidepressants are assessed and their clinical efficacy demonstrated are not always robust. That current clinical comparisons of antidepressants rarely show major differences in efficacy between existing molecules could be taken as an indication that "all drugs are the same" or perhaps, more insightfully, as an indication that the ubiquitous Hamilton depression (HAM-D) rating scales are not sensitive to inter-drug differences, even though pronounced pharmacodynamic differences between molecules are easily demonstrated. Any advances in the development of new antidepressants will have to find not only original compounds but also unique psychometric tests by which the drugs can be assessed in a sensitive, reliable, and valid manner.

Brain-Derived Neurotrophic Factor↗
PubMed2002

An evaluation of the effects of high-dose fexofenadine on the central nervous system: a double-blind, placebo-controlled study in healthy volunteers.

BACKGROUND: As regards central nervous system (CNS) effects there are three types of antihistamines. Those that cross the blood-brain barrier and cause widespread impairment of cognitive and psychomotor function; those that cross into the brain and, although without much impairment at low clinical doses, have a dose-related relationship to impairment; and those that do not cross into the brain and therefore possess no intrinsic potential for impairing CNS function. OBJECTIVE: [corrected] To investigate the acute effects of fexofenadine (360 mg) on various aspects of cognitive and psychomotor function in comparison to placebo and promethazine (positive internal control), an antihistamine known to produce psychomotor and cognitive impairment. METHODS: Fifteen healthy volunteers received fexofenadine 360 mg, promethazine 30 mg and placebo in a 3-way cross-over, double-blind study. For each treatment condition, subjects were required to perform a series of tests of cognitive function and psychomotor performance at baseline and 1, 3, 5 and 7 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and a subjective assessment of sedation (LARS). RESULTS: Fexofenadine was not distinguishable from placebo in any of the objective and subjective tests for up to seven hours following drug administration. However, all measures were significantly impaired following the administration of promethazine, which confirms the sensitivity of the test battery for sedation. The effects of fexofenadine and placebo were not significantly different from one another, whereas promethazine caused an overall reduction in CFF thresholds when compared to placebo (P < 0.05). There was an overall significant increase (impairment) in recognition, motor and total reaction time (P < 0.05), and both the tracking accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05) following the administration of promethazine. In contrast, the effects of fexofenadine could not be distinguished from the placebo condition. Subjective ratings of sedation were significantly higher with promethazine when compared to placebo (P < 0.05) and fexofenadine (P< 0.05). CONCLUSIONS: Fexofenadine at a dose of 360mg is demonstrably 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. The identification of an antihistamine (fexofenadine) devoid of central effects even at supraclinical doses separates it from currently available first and second generation drugs with no objective evidence of CNS side-effects on cognition and psychomotor function, and highlights the need for the introduction of a third generation of non-sedative antihistamines.

Adult↗
PubMed2001

Effects of tianeptine and mianserin on car driving skills.

RATIONALE: Tianeptine is a novel antidepressant which enhances the reuptake of serotonin (5-HT). Previous studies suggest that tianeptine has a non-sedative side-effect profile, but its effects on everyday activities including car driving have not been fully explored. OBJECTIVES: To assess the effects of tianeptine on tests related to car driving performance. METHOD: Sixteen healthy volunteers received acute doses of tianeptine 12.5 mg and 37.5 mg, mianserin 30 mg and placebo in a double blind four-way crossover study. The effects of treatment on self assessed ratings of sedation (LARS), two valid and reliable laboratory performance measures, critical flicker fusion (CFF) and choice reaction time (CRT) and an "on-the-road" measure of one aspect of car driving performance, brake reaction time (BRT) were examined. The BRT test was administered at baseline and at 1.5, 3, 4.5 and 6 h post-dose, while LARS, CFF and CRT were administered at baseline and at 1, 2, 4 and 5 h post-dose. For all data, the maximum change from baseline was calculated and used in the analysis. RESULTS: Tianeptine had no measurable effect on performance, compared to placebo, on any of the variables investigated. Compared to placebo, mianserin was shown to lower CFF thresholds (P = 0.01), increase reaction times on both the CRT (P = 0.001) and the BRT (P = 0.01) tests and was subjectively rated as more sedative than placebo (P = 0.01). CONCLUSION: The apparent lack of counter-therapeutic side-effects produced by an acute dose of tianeptine suggest that it may be a suitable antidepressant for use in an ambulant population.

Adult↗
PubMed2001

An investigation into the effects of cetirizine on cognitive function and psychomotor performance in healthy volunteers.

OBJECTIVE: The cognitive and psychomotor effects of 2.5, 5 and 10 mg cetirizine, a second-generation H1 receptor antagonist, were compared with loratadine 10, 20 and 40 mg, promethazine 25 mg and placebo in 24 healthy volunteers in a double-blind, randomised cross-over study. METHODS: Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3 and 6 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and assessment of subjective sedation (LARS). RESULTS: Cetirizine and loratadine at all doses tested were not significantly different from placebo in any of the tests used. However, as expected for a verum, all measures with the exception of CTT were significantly disrupted by promethazine (P < 0.05). Promethazine caused a reduction in CFF threshold at all test points; these differences were significant at 3 h and 6 h post-dose (P < 0.05). There was also a significant increase in total reaction time at 3 h post-promethazine administration. Subjective reports of sedation were significantly greater following the administration of promethazine at all time points (P < 0.05). CONCLUSIONS: These results allow the conclusion that cetirizine at its recommended therapeutic dose of 10 mg is demonstrably 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 positive control, promethazine 25 mg.

Adult↗
PubMed2001

The Alzheimer's disease activities of daily living international scale (ADL-IS).

BACKGROUND: Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimer's disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD: An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS: An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION: This scale can be used to measure therapeutic response in AD.

Activities of Daily Living↗
PubMed2001

Forensic urinalysis of drug use in cases of alleged sexual assault.

The results of 3303 analyses of urine samples, collected in an independent testing programme from individuals who claimed to have been sexually assaulted and believed that drugs were involved, were examined in detail. Of the samples provided, 2026 (61.3%) proved positive for one or more substances. Alcohol, either alone or in combination with other drugs, was by far the commonest substance found, being present in 1358 samples (67.0% of positives). Cannabis was the second most prevalent drug, present in 613 samples, (30.3% of positives). Detailed examination of the testing results does not support the contention that any single drug, apart from alcohol, can be particularly identified as a 'date rape' drug. Rather, the alleged sexual assaults may often take place against a background of licit or recreational alcohol or drug use, where alcohol and other drugs are frequently taken together. The extensive forensic database examined here does not support the concept of a commonly occurring 'date rape' scenario, in which the victim's drink is covertly 'spiked' with a tablet, capsule or powder containing a sedative-hypnotic. This research highlights the need for the early collection of forensic samples in cases of alleged sexual assault. Law enforcement agencies and health professionals should establish guidelines and procedures to ensure that appropriate forensic samples (blood and urine) are collected in a timely manner following allegations of possible drug mediated sexual assault.

Journal Article↗
PubMed2001

The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare.

AIM: To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (L-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments. METHODS: Twenty healthy volunteers (18-50 years) received L-CTZ 5mg, CTZ 10 mg, LOR 10 mg, PRM 30 mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100 mg/ml histamine solution at baseline and at 1, 2, 3 ,4, 6, 8, 10 and 122 hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit. RESULTS: The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p < 0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p < 0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p < 0.005) and significantly higher ratings of subjective sedation on day 1 (p < 0.05). L-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, L-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4. CONCLUSIONS: In a study where the psychometric assessments were shown to be sensitive to impairment, L-CTZ 5 mg was found following both initial and repeated doses, but also to be demonstrably free from disruptive and sedative effects on objective measures of psychomotor and cognitive function. Similarly, CTZ showed evidence of pronounced antihistaminic activity and significantly reduced weal and flare scores after both acute and repeated doses, again without evidence of cognitive or psychomotor impairment. LOR also was non-sedative but the antihistaminic reaction was demonstrably weak.

Adult↗
PubMed2001

Pharmacokinetic profile of loprazolam in 12 young and 12 elderly healthy volunteers.

The aim of the study was to investigate the pharmacokinetic profile of acute and steady state doses of loprazolam (1 mg) following nighttime administration in 12 young (18-30 years) and 12 elderly (60-80 years) nonfasting subjects. Loprazolam blood plasma concentration was determined by high-performance liquid chromatography with ultraviolet absorption detection. The drug was isolated from the plasma using a solid phase extraction procedure. On day 1 subjects were breathalyzer and given a brief medical examination. Baseline blood samples (10 ml) were taken via a venous cannula at -1.5 to -0.25 h prior to drug administration. Loprazolam was administered at 21.00 and further blood samples were taken at 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 5, 6, 8, 10, 12, 18 and 23.5 h (baseline sample for day 2). On subsequent days (days 2, 3 and 4) blood samples were taken at -0.5 and 2 h. The schedule for day 1 was repeated for day 5 with the test period ending at 21.30 on day 6. Significant changes in the pharmacokinetics of the drug were evident in the elderly volunteers compared with the young volunteers following steady state, where tmax was significantly prolonged (CI 90% = 0.80 to 1.25; p < 0.00006) and a decline was observed in peak plasma concentration (CI 90% = 0.80 to 1.25; p < 0.00006). However, no statistically significant difference was found between the two groups in either the elimination half-life of the drug or the area under the curve. Loprazolam appears to be well tolerated by both the young and the elderly and only mild adverse effects were reported after nighttime administration. These results provide valuable data on the pharmacokinetics of the drug in normal clinical practice.

Adolescent↗
PubMed2000

The effects of Ginkgo biloba extract (LI 1370) supplementation on activities of daily living in free living older volunteers: a questionnaire survey.

This survey assessed the impact of four months supplementation with 120 mg/day of the standardized Ginkgo biloba special extract (LI 1370) on activities of daily living and various aspects of mood and sleep in a population of free living older volunteers using both observer- and self-rated scales. 5028 Participants (mean age 68.9 years) were recruited through a magazine editorial. One thousand received Ginkgo biloba extract (GBE) and the remainder were allocated to the Control group. The B-ADL (activities of daily living) Scale was completed at baseline and at the end of month 4 by an informant familiar with the participant, a Self-rating ADL scale and Line Analogue Ratings Scales of mood and sleep were completed by the participants at the end of months 1, 2, 3, and 4. There were significant differences between the GBE and Control groups on all scales at each time point. The GBE group felt better able to cope with their daily activities and showed positive changes in mood and sleep compared to the Control group. These results suggest that GBE supplementation has beneficial effects on areas of functioning that have implications for quality of life in an older population. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

Sedation and antihistamines: a review of inter-drug differences using proportional impairment ratios.

The use of antihistamines (AHs) 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. The first, an objectively determined measure based on the results of psychometric tests from controlled trials, and the second, the subject's response to the administration of a drug. Since AHs are largely used in ambulant patients, a complete evaluation of sedation should be performed through standardised objective and subjective tests, shown to be sensitive to the central effects of AHs.An extensive review of the literature identified 76 studies of H(1) receptor antagonists in healthy volunteers, in which assessment of sedation was the primary objective. Results from studies published in peer-reviewed journals which employed a placebo condition as well as a positive internal control using a crossover design were analysed to determine the extent to which a particular antihistamine produced impairments on a battery of psychometric tests. The impairment index for each antihistamine was calculated and subsequently compared with the impairment index obtained for all other AHs.The calculation of this proportional impairment ratio enabled the sedative potential of an individual antihistamine to be identified relative to all other AHs and thus allowed the ranking of AHs with respect to their ability to cause impairments of cognitive and psychomotor function.Findings from this review clearly demonstrate that there are distinct classes of AHs with respect to their ability to impair cognitive function and psychomotor performance. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

A naturalistic investigation of the effects of day-long consumption of tea, coffee and water on alertness, sleep onset and sleep quality.

RATIONALE: The effects of caffeine, especially caffeinated coffee, on human performance have been extensively studied. However, few studies have been naturalistic representations of how tea/coffee is normally consumed in terms of dose and time of consumption. OBJECTIVES: This study investigated the effects of day-long consumption of tea, coffee and water on cognitive and psychomotor performance, and sleep quality at night. METHODS: Thirty healthy volunteers received equal volume drinks equivalent to either 1 or 2 cups of tea (containing 37.5 mg or 75 mg caffeine), or coffee (75 mg or 150 mg caffeine), or water, in a randomised five-way crossover design. Drinks were administered on four occasions during the day (0900, 1300, 1700 and 2300 hours). A psychometric battery consisting of critical flicker fusion (CFF), choice reaction time (CRT) and subjective sedation (LARS) tests, was administered pre-dose and at frequent time points post-dose. The Leeds Sleep Evaluation Questionnaire (LSEQ) was completed each morning and a wrist actigraph was worn for the duration of the study. RESULTS: Caffeinated beverages maintained CFF threshold over the whole day (P<0.05), independent of caffeine dose or beverage type. During the acute phase of beverage ingestion, caffeine significantly sustained performance compared to water after the first beverage for CFF and subjective sedation (P<0.05), and after the second beverage for the Recognition component of the CRT task (P<0.05). Additionally, there were significant differences between tea and coffee at 75 mg caffeine after the first drink. Compared to coffee, tea produced a significant increase in CFF threshold between 30 and 90 min post-consumption (P<0.01). However, following the second beverage caffeinated coffee at 75 mg significantly improved reaction time (P<0.05), compared to tea at the same dose, for the Recognition component of the CRT task. Caffeinated beverages had a dose dependent negative effect on sleep onset (P<0.001), sleep time (P<0.001) and sleep quality (P<0.001). CONCLUSIONS: These results indicate that ingestion of caffeinated beverages may maintain aspects of cognitive and psychomotor performance throughout the day and evening when caffeinated beverages are administered repeatedly. This study also demonstrates that day-long tea consumption produces similar alerting effects to coffee, despite lower caffeine levels, but is less likely to disrupt sleep. Other differences between tea and coffee were more subtle, and require further investigation.

Adult↗
PubMed2000

Pharmacodynamics of milnacipran in young and elderly volunteers.

AIMS: To investigate the pharmacodynamics of milnacipran in healthy young and elderly volunteers. METHODS: Randomized double-blind crossover designs were employed and a standardized psychometric battery was administered pre and post dose for both studies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per day, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days' dosing in healthy volunteers aged over 65 years. The test battery was administered at baseline and at 2, 10 and 24 h post dose. The psychometric battery included critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT) and tests of short-term memory (STM), subjective sedation (LARS) and subjective sleep (LSEQ). RESULTS: Milnacipran produced no significant dose related effects in the young volunteers. For the elderly, milnacipran significantly (P<0.05) raised CFF scores compared with placebo but had no significant effects on any of the other measures used. Amitriptyline, in contrast, significantly (P<0. 05) lowered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. CONCLUSIONS: The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance. In addition, milnacipran 75 mg (50+25 mg) appears to be free of negative effects on cognitive function in elderly volunteers, where it seemingly improves performance on CFF. In contrast, the tricyclic antidepressant amitriptyline, used here as a positive internal control, significantly impaired performance in the elderly on the majority of psychometric measures used in this study. This finding not only validated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elderly.

Adult↗