bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose related effects of trimipramine on psychomotor function, memory, and autonomic nervous system activity in healthy volunteers
Authors: Warot D. , Molinier P. , Lacomblez L. , Payan C. , Danjou Ph. , Puech A. J.
Published: December 2004

The effects of single doses of trimipramine, a tricyclic antidepressant (25, 50 and 100 mg) and placebo on psychomotor performance, memory, haemodynamics, pupil diameter and salivary volume, were assessed in 12 normal volunteers. All subjects received each of the four treatments, at weekly interval, according to a double‐blind cross‐over Latinsquare design.

Treatments effects were monitored using a battery of tests including critical flicker fusion (CFF), choice reaction time (CRT), subjective ratings of mood and memory tasks before, and 3 and 8 hours following medication. Supine standing blood pressure, pupil diameter and salivary volume were recorded at the same times.

Compared to placebo, trimipramine impaired both subjective and objective measures in a dose‐related manner, with 25 mg affecting some subjective ratings and CFF, and 100 mg impairing most objective and subjective evaluations, except memory and haemodynamic variables. Pupil diameter was reduced by 50 and 100 mg trimipramine, whereas salivary volume was affected only by the highest dose studied.

In conclusion, the sedative effects of trimipramine appeared dose‐related. No amnesic effect could be evidenced, at the doses studied. Changes in autonomic nervous system activity have been shown on pupil diameter and salivary secretion.
Stimulation of growth hormone secretion by baclofen in man: Failure to confirm published findings
Authors: Markar Hameen , Bennie John , Carroll Sheena , Chiswick Ann , Wilson Helen , Goodwin Guy M.
Published: December 2004

The effects upon growth hormone (GH) secretion of oral baclofen were determined in 20 male volunteers. Doses of either 5 mg or 0·25 mg/kg (approx. 20 mg) of baclofen were employed. No stimulation of growth hormone secretion could be discerned in the 90 min following ingestion, a result which is in contrast with the findings of a previous study. We conclude that stimulation of GH secretion by baclofen at low doses does not provide a ready assay of GABAB function in man.
The role of calcium in the pharmacology of mania
Authors: Dinan Timothy G. , Elphick Martin , Sharp Trevor
Published: December 2004

Episodes of mania in bipolar affective disorder patients are associated with a decrease in cerebrospinal fluid calcium. A reduction in extracellular calcium in most neurones leads to a decrease in calcium‐activated potassium conductance mechanisms. Such mechanisms help govern the rate of action potential generation by neurones, and thus the rate of information processing. The dopamine hypothesis of neuroleptic action cannot explain the antimanic actions of lithium, calcium antagonists or carbamazepine. This paper proposes a common mechanism of action for such substances — namely, an action on calcium‐activated potassium conductances.
‘Jet‐lag’: Strategies for prevention and cure
Authors: Redfern P. H.
Published: December 2004

In this review the phenomenon of jet‐lag is described and the causal mechanisms are considered. The theoretical basis for a variety of pharmacological and non‐pharmacological treatments designed to alleviate the symptoms of jet‐lag is discussed, and the evidence of clinical efficacy is outlined. The wider implications of jet‐lag as a possible model of circadian abnormalities underlying mental disorders is briefly considered.
EEG‐Brain mapping, psychometric and psychophysiological studies on central effects of kavain ‐ a kava plant derivative
Authors: Saletu B. , Grünberger J. , Linzmayer L. , Anderer P.
Published: December 2004

In a double‐blind, placebo‐controlled study the encephalotropic and psychotropic effects of kavain‐a synthetic kava plant derivative as compared with clobazam were investigated, utilizing EEG brain mapping, psychometric and psychopysiological analyses. 15 normal volunteers received randomized in weekly intervals single oral doses of placebo, 200 mg, 400 mg and 600 mg kavain as well as 30 mg clobazam as reference compound. EEG recordings, psychometric tests, evaluations of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6 and 8. Brain maps of drug induced pharmaco‐EEG changes (pharmaco‐EEG maps) demonstrated that kavain exerted a significant action on the human brain function as compared with placebo characterized by a dose‐dependent increase of delta, theta and alpha 1 activity while alpha 2, beta activity and the centroid of the total activity decreased. These findings are indicative of a sedative effect which was, however, in type quite different from that of the 1·5 benzodiazepine. The latter produced a decrease of delta, theta, alpha 1 and alpha 2 and an increase of beta activity while the total centroid was accelerated. Interestingly, 200 mg kavain induced with a decrease of delta and beta activity and an increase of alpha activity and of total power also vigilance promoting effects. Psychometric investigations demonstrated also clear differences between the two compounds at the behavioural level. Kavain improved the noopsyche as compared with placebo in all 3 doses as there was a significant improvement in intellectual performance (Pauli test), attention, concentration, reaction time and motor speed (rigidity test), while opposite findings were observed after 30 mg clobazam. In regard to thymopsychic variables such as drive, wakefulness, affectivity, mood, well‐being, 200 mg kavain produced an improvement as compared with placebo while 600 mg kavain produced sedation as did 30 mg clobazam. Psychophysiological evaluations resulted in only minimal findings. Time efficacy calculations demonstrated after kavain a pharmacodynamic peak in the 1st to the 2nd hour then a drop and a second peak in the 8th hour while clobazam produced maximal central effects in the 1st hour which declined thereafter to show a second peak in the 6th hour. Topographically, most encephalotropic effects were found after kavain in the frontal, after clobazam in the central and parietal areas. Evaluations of pulse, blood pressure and side effect demonstrated good tolerability of both compounds with 30 mg clobazam producing more sedation than kavain.
The prescribing of antidepressants in general practice. II: A placebo‐controlled trial of low‐dose dothiepin
Authors: Thompson C. , Thompson C. M.
Published: December 2004

General practitioners rarely treat depressed patients with more than 75 mg of a tricyclic antidepressant. This is thought to be a subtherapeutic dose for depression seen in the setting of a psychiatric hospital, but has been thought to be effective for treating the milder, mixed anxiety depressive states of general practitioners. This double‐blind placebocontrolled trial of the commonest tricyclic in use, dothiepin, at 75 mg per day, demonstrates that there is no advantage over placebo in the prescription of this dose of dothiepin. Indeed on measures of depression and somatic symptoms placebo had a significant advantage in the group who completed the trial. Dothiepin caused more side‐effects.
Cerebral uptake of 11C—Ro 15—1788 and its acid metabolite 11C—Ro 15—3890; PET study in healthy volunteers
Authors: Persson A. , Pauli S. , Swahn C. G. , Halldin C. , Sedvall G.
Published: December 2004

The benzodiazepine antagonist Ro 15–1788 and its acid metabolic product Ro 15–3890 were labelled with 11C and used in a PET study to examine their ability to penetrate the blood‐brain barrier in man. After intravenous administration to healthy volunteers, 11C‐Ro 15–1788 immediately accumulated to a large extent in the brain, where about 5 per cent of the dose injected was still present after 20 min. 11C‐Ro 15–3890, on the other hand, did not accumulate significantly in the central nervous system. At 20 min after the injection less than 0·1 per cent of the radioactivity injected was present in the brain. The results allow the conclusion that the acid metabolite of Ro 15–1788 formed by peripheral metabolism does not significantly contribute to brain radioactivity levels after intravenous injection of 11C‐Ro 15–1788 to man. The results also demonstrate the potential of the PET technique to analyse pharmacokinetic aspects of drug transport into the central nervous system in man.
On the elimination half‐life of lithium in long‐term treatment of patients with affective disorders
Authors: Nilsson Agneta , Axelsson Rolf
Published: December 2004

The elimination half‐life of lithium was investigated in 55 patients on long‐term treatment in 1980, when their mean treatment time was 7·5 years. Twenty‐seven of the patients were reinvestigated 7 years later, at which point their mean treatment time was 15 years. An approximate method for determining the elimination half‐life of lithium was used, and this variable was tested in eight chronic psychotic patients on lithium treatment, in whom the elimination half‐life was also determined by a conventional technique. The elimination half‐life was 32 h in 1980 and varied between 15 and 128 h. The elimination half‐life was significantly increased 7 years later, with a median increase of 8 h. The elimination half‐life of lithium was closely correlated to age and to daily weight‐related dose of lithium when the patients entered the study in 1980, but this was not seen at the time of the reinvestigation in 1987. The elimination half‐life did not vary with serum creatinine, maximal urine osmolality, or with the concomitant neuroleptic medication. Further studies are needed to clarify the clinical significance of the prolonged elimination half‐life with time.
The effects of alcohol on skilled and moderately skilled subjects on measures of perceptual‐motor skill
Authors: Golby J.
Published: December 2004

Fourteen normal female volunteers were allocated to either a ‘skilled’ or a control group. All subjects received acute doses of 0·8 g/kg absolute alcohol or placebo equivalent. Performance on a number of tests of cognitive functioning and perceptual‐motor skill was recorded commencing 30 min following treatment. The tests used were critical flicker fusion (CFF), gross‐bodily choice reaction time (GBCRT), ball control (CONT), slalom (SLAL) and shooting (SHOOT). Although alcohol did not significantly impair performance, results suggested a discernible trend, with the skilled performers being more able to withstand the alcohol‐induced impairment.
The effects of lormetazepam on aspects of memory, sleep and human performance
Authors: Dye Louise , Alford C. , Bhatti J. Z. , Hindmarch I.
Published: December 2004

The effects of lormetazepam 1 mg, 1·5 mg, 2 mg, a verum—triazolam 0·5 mg and placebo were examined in ten normal female volunteers, on tests of psychomotor function, performance and analogue rating scales for subjective sedation, sleep and early morning behaviour. Results showed all doses of lormetazepam to be effective hypnotics and free from residual effects 10 h after drug ingestion when tested on critical flicker fusion threshold (CFF), choice reaction time (CRT), simultated car tracking task and Maddox wing. Acquisition and immediate recall of word lists was poorer following administration of lormetazepam 1·5 mg and triazolam 0·5 mg. On memory scanning, lormetazepam 1 mg was the only dose completely free from residual impairment 10 h following administration.
Flumazenil and saccadic eye movements in patients with panic disorder and normal controls
Authors: Wilson Sue , Glue Paul , Nutt David
Published: December 2004

The effects of the benzodiazepine receptor antagonist flumazenil on saccadic eye movements were studied in patients with panic disorder and in controls. Compared with vehicle, flumazenil displayed slight partial agonist effects in that it significantly reduced peak deceleration of eye movements, with a similar but non‐significant trend for peak velocity, in both groups. In controls flumazenil had little in the way of subjective effects whereas in panic patients it produced marked anxiety. The paradoxical responses to flumazenil in panic disorder (partial agonist effects on saccadic eye movements but partial inverse agonist effects on mood) may be due to different receptor subtypes controlling these variables.
Variation in platelet [3H]imipramine binding during the menstrual cycle in healthy young women
Authors: Ellis Peter M. , McIntosh C. Joy , Cooke Russell R.
Published: December 2004

Platelet [3H]imipramine binding, a putative biological marker for depression, varies considerably among healthy control subjects. This study examined whether changes associated with the menstrual cycle could account for part of this variability. No significant relationship was found between Bmax or Kd and the phase of the menstrual cycle, or symptoms associated with the premenstrual syndrome or progesterone or oestradiol levels. Other factors should be considered in exploring the variability of[3H]imipramine binding in healthy subjects.
The effects of alcohol on the cognitive function of males and females and on skills relating to car driving
Authors: Kerr J. S. , Sherwood N. , Hindmarch I. , Bhatti J. Z. , Starmer G. A. , Mascord D. J.
Published: December 2004

Nine male and nine female subjects received one of four doses of alcohol (0‐25, 0‐5, 0‐75 or 1 g per kg of bodyweight for male subjects: females received 92% of these values) or placebo. Similar blood alcohol concentrations (BAC) for males and females were reached. Subjects were then tested on two batteries of psychological tests related to skills involved in driving. These included psychomotor, cognitive and subjective assessment tasks. The results showed a linear increase in the disruption of performance with dose for many of the tests, particularly those involving psychomotor function. In addition it was demonstrated that on certain tasks males were affected more by alcohol than females. It is concluded that moderate doses of alcohol (resulting in BACs of 0‐05 to 0‐08 g/100 ml) can produce significant deficits in perceptual and motor skills related to driving a vehicle.
The effect of anticonvulsant medication on the psychopathology of adults with a mental handicap and epilepsy
Authors: Deb S. , Hunter D.
Published: December 2004

Different aspects of anticonvulsant treatment and psychopathology were studied in a group of 150 adult epileptic mentally handicapped patients and compared with a matched control group of 150 adult non‐epileptic mentally handicapped people. Patients were collected from both hospital and community. Most epileptic patients received monopharmacy of the modern generation of anticonvulsants within the British National Formulary recommended dosage schedule. Most had their serum anticonvulsant level within the local laboratory reference range. Anticonvulsants other than sodium valproate lowered serum folate level. In general there was no direct relationship with anticonvulsant medication and psychopathology, although carbamazepine monopharmacy showed some protective effect on aggressive behaviour.
PET analysis of central [11 C]raclopride binding in healthy young adults and schizophrenic patients—reliability and age effects
Authors: Nordström A.‐L. , Farde L. , Pauli S. , Litton J.‐E. , Halldin C.
Published: December 2004

Central D2‐dopamine receptor occupancy determined by positron emission tomography (PET) during neuroleptic drug treatment may be a useful measure for optimal dose finding in schizophrenic patients. The clinical benefit is dependent on the reliability of such determinations. The ratio of radioactivity in the striatum to that of the cerebellum is widely used for calculation of D2‐receptor occupancy and as an index of D2‐dopamine receptor density. To test the reliability of such ratios a test‐retest analysis was performed in a series of healthy subjects. The reliability was very high, both when experiments were repeated on the same day and after time intervals of months to years. A group of subjects were examined twice using PET camera systems with different resolution. The striatum to cerebellum ratios obtained from the high‐resolution PET camera system were significantly higher than ratios from the camera with lower resolution. The age effect on the striatum to cerebellum ratio was examined in 25 healthy young adults and in 18 neuroleptic‐naive schizophrenic patients. A statistically significant decline was found both in the healthy controls and in the schizophrenic patients. The results do not support the view that there is a lack of age effect on the D2‐dopamine receptor density in schizophrenia.
Who prescribes antidepressant drugs? A survey of a sample of pharmacies in Verona, Italy
Authors: Balestrieri M. , Paltrinieri E. , Bellantuono C.
Published: December 2004

A 4‐week cross‐sectional survey was undertaken on a sample of 24 pharmacies in the city of Verona (Italy). The aims were: (1) to describe the distribution of antidepressant drugs (AD) prescription according to the type of prescriber (GP, psychiatrist, ‘other physician’) and (2) to analyse the relationship between class of AD, type of prescriber and age/sex of patients. GPs were responsible for 31 per cent, psychiatrists for 61 per cent and ‘other physicians’ for 8 per cent of all AD prescriptions (852). Using a log‐linear model, we found that tricyclics were mainly prescribed by ‘other physicians’, followed by psychiatrists and least by GPs. Psychiatrists and GPs prescribed more tricyclics to older patients. The pattern of prescription of second‐generation AD was similar across all groups of prescribers. Older patients received more of these drugs than younger patients. Ademetionine was prescribed mainly by GPs. The rate of prescription of this drug declined with the age of the patients. A need for more data of this type, and for development of educational programmes on antidepressant drug use, is discussed.
Does cetirizine belong to the new generation of antihistamines? An investigation into its acute and subchronic effects on highway driving, psychometric test performance and daytime sleepiness
Authors: Volkerts E. R. , van Willigenburg A. P. P. , van Laar M. W. , Maes R. A. A.
Published: December 2004

Twenty‐seven healthy male volunteers participated in a double‐blind, five‐way crossover designed comparison of the new, selective H1‐receptor antagonist cetirizine (10 mg q.d.) and terfenadine (60 mg b.i.d. and 120 mg q.d.) versus the older H1‐receptor antagonist triprolidine (5 mg b.i.d.) and placebo.

Medication was administered during four consecutive days. Subjects were tested on the 1st and 4th treatment day. On each test day subjects drove an instrumented vehicle over a 100 km highway circuit while attempting to maintain a constant speed (90 km/hr) and a steady lateral position within the right traffic lane. Thereafter they performed three computerized memory tasks. On the 4th treatment day, sleep latency was measured before and after the driving test. On both days, triprolidine significantly impaired performance in the driving and psychometric tests. Triprolidine also significantly reduced sleep latency in comparison to placebo on the 4th treatment day. Terfenadine 60 mg b.i.d. impaired psychometric performance after subchronic treatment.

It was concluded that cetirizine, like terfenadine, belongs to the newer class of antihistamines and can be safely used by patients who continue their daily activities.
Alpidem and lorazepam in the treatment of patients with anxiety disorders: Comparison of efficacy and rebound
Authors: Morton S. , Lader M.
Published: December 2004

Alpidem, a novel imidazo‐pyridine anxiolytic, was compared with lorazepam for efficacy and withdrawal effects in 23 (17 male) anxious psychiatric out‐patients of mean age 35.3 years with a mean Hamilton Anxiety Rating Scale (HAM‐A) total score of 26.4. Treatment was double blind for 4 weeks with doses built up to a mean of 112.5 mg alpidem and 3.5 mg lorazepam per day. Assessment were made for a further 2 weeks after abrupt withdrawal.

There were no differences in scores between the groups before treatment. The HAM‐A, Hospital Anxiety and Depression Scale, Sleep Rating Scale and other measures showed both drugs to be equally effective for psychic and somatic anxiety, depression and insomnia. Despite the small numbers, lorazepam produced greater improvement in the anxious mood, fear and insomnia items of the HAM‐A. After stopping treatment serious rebound in mood and somatic scores was experienced by the lorazepam group in contrast to those patients on alpidem who maintained their improvement. Neither group was troubled by side effects; dropouts were few and due to inefficacy (1 alpidem) or withdrawal problems (2 lorazepam). Alpidem seemed to offer effective anxiolysis without the risk of rebound associated with lorazepam use.
Clovoxamine fumarate: Antidepressant or anxiolytic?
Authors: Edwards J. Guy , Goldie Ann
Published: December 2004

A randomised placebo‐controlled trial of clovoxamine fumarate was carried out in 44 outpatients with major depression. Patients were rated on scales for depression and anxiety after a one‐week washout period and after two and four weeks' treatment with either clovoxamine or placebo. There were no significant differences between the two groups in the total depression scores, but a significant difference in favour of clovoxamine in the Leeds Self‐Assessment of Anxiety General Scale. Unwanted effects in both groups were mild but gastrointestinal symptoms occurred more often and lasted longer in patients receiving clovoxamine. The question as to whether clovoxamine is an antidepressant or an anxiolytic is addressed and the specificity of action of psychotropic drugs in general discussed.
Effects of benzodiazepine‐induced sedation on temporal processing
Authors: Rammsayer Thomas
Published: December 2004

Unlike processing of time intervals in the range of seconds or more, processing of brief durations ranging from approximately 50 to 100 ms appears to be beyond cognitive control and based on neural counting mechanisms. In a placebo‐controlled study either 15 mg of midazolam or placebo were applied to 36 healthy male volunteers to investigate the effect of pharmacologically induced sedation on temporal processing of intervals in the range of milliseconds indicating performance on time perception and in the range of seconds indicating performance on time estimation. In addition, a test battery consisting of subtests measuring speed of information processing and cortical arousal was applied. Midazolam induced a very pronounced decrease in cortical arousal as well as a marked impairment of speed of information processing and performance on time estimation as compared to placebo. Performance on time perception, however, was not affected suggesting that temporal processing of very brief intervals is unrelated to the effective level of cortical arousal. These findings support the notion of two different timing mechanisms underlying time estimation and time perception.
The effect of vigabatrin on cognitive function and mood
Authors: Dijkstra J. B. , McGuire A. M. , Trimble M. R.
Published: December 2004

Cognitive function and mood have been assessed in nine patients started on vigabatrin as additional therapy to their regular anticonvulsants. Psychological tests were given at baseline (S1) and at 4 weeks (S2) after starting treatment. A comparison group of nine patients on stable therapy was tested at the same time intervals. In particular, tasks with minimal or no motor components were used. Mood was rated with the Beck Depression Inventory. The vigabatrin group scored significantly higher on a task of attention and concentration at S2. This was not related to change of seizure frequency or serum levels of other anticonvulsants. No effects were observed on mood.
Steady‐state serum kinetics of zotepine
Authors: Otani K. , Kondo T. , Kaneko S. , Hirano T. , Mihara K. , Fukushima Y.
Published: December 2004

The steady‐state serum kinetics of zotepine, an antipsychotic drug, were studied in 59 psychiatric in‐patients receiving 50–500 mg/day (mean 215 mg/day) of the drug. There was a 26‐fold inter‐individual variation in the concentration/dose ratios (C/D ratios: ng/ml/mg/kg), which ranged from 2.4 to 62.2 (mean 13.2). The smokers (n = 37) had significantly lower C/D ratios (mean ±SD: 9.7 ± 7.0 vs 19.0 ± 15.5, p < 0.01), while the patients co‐administered benzodiazepines (n = 14) had significantly higher C/D ratios (19.06 ± 12.5 vs 11.2 ± 10.9, p < 0.01) than the others. There was no significant relationship between the C/D ratios and age or gender. In the 24 cases where the dose was fixed at 100 mg/day in the first week and at 200 mg/day for the next 3 weeks, no significant difference was found in the mean C/D ratios during the 4 weeks. The present study thus suggests a large inter‐individual variation in the metabolism of zotepine, and that smoking enhances, and co‐administration of benzodiazepines inhibits, the metabolism. Age and gender do not affect the kinetics of the drug. The results also suggest no dose‐dependent kinetics and no enzyme‐inducing effect of the drug.
Recruitment rates and factors affecting recruitment for a clinical trial of a putative anti‐psychotic agent in the treatment of acute schizophrenia
Authors: Bowen Joanna , Hirsch Steven
Published: December 2004

Prospectively collected data on screening of 166 patients for a placebo controlled double blind clinical trial of a putative anti‐psychotic drug was analyzed to establish the rate of recruitment of patients in an academic centre known for its interest in schizophrenia and its associated hospitals. Screening of patients was carried out intensively. A descriptive analysis was carried out on why otherwise eligible patients did not consent to enter the trial, and on why patients were not eligible to be entered, either because of physical or psychiatric morbidity. Social demography and morbidity were compared between the subgroups of consenting and non consenting eligible patients. No differences were detected between the demography and morbidity level of the consenters and non‐consenters. Nearly 60 per cent of patients screened were ineligible to enter the trial. Reasons for ineligibility are discussed. Of patients eligible 66 per cent were not willing or able to give their consent. This meant that overall, about 1 in 7 of all patients screened were able to be entered into the trial.
Potential effect of enalapril on clomipramine metabolism
Authors: Toutoungi M.
Published: December 2004

In two patients treated for hypertension with enalapril for more than 12 months, clomipramine was introduced in small to moderate doses for the treatment of dysthymic disorders. Rapid improvement of depressive symptoms was noted, which was followed by signs of antidepressant overdosage. The blood levels of clomipramine and desmethylchlomipramine were high. After reducing the dose, the symptoms resolved and the blood level of antidepressant returned to the usual therapeutic range. Enalapril would appear to reduce the clearance of clomipramine; the association enalapril + clomipramine does not appear to modify blood pressure.
A case of neuroleptic malignant syndrome with a history of general anesthesia
Authors: Sato T. , Hara T. , Takeichi M.
Published: December 2004

Antidepressant was given to treat a patient with manic‐depressive psychosis, depressed type (ICD‐9). Following the treatment, she manifested the alteration of the consciousness, autonomic dysfunction, extrapyramidal sign, muscular hypertonicity, hyperthermia, and elevated serum CPK levels. This condition was consistent with the neuroleptic malignant syndrome. Then, along with interruption of medication she was treated with supportive measures and improved progressively.

In her past history, she underwent general anesthesia for operation of mitral valve replacement and at that time she manifested tachycardia, hyperthermia, elevated CPK levels, etc. In the case of patients who manifest a malignant hyperthermia‐like state or neuroleptic malignant syndrome‐like state, special care is required in selecting anesthetics and psychotropic drugs.
The effects of caffeine and automaticity on a visual information processing task
Authors: Loke Wing Hong
Published: December 2004

The present study examined caffeine's effect on mental performance in contrast to a recent study (Loke and Goh, 1992) which examined the effects of caffeine user‐effect on mental performance. Taken together, the studies would provide a detailed understanding of the effects of caffeine and automaticity on the visual search/detection domain of information processing. Analyses of the baseline measures of the visual search/detection task showed significant differences between low and high levels of automaticity and levels of task difficulty. Performance on the low difficulty level was higher than the high difficulty level, and performance on automatic task was higher than on non‐automatic task. Caffeine, however, did not interact with automaticity and task difficulty. Therefore, given that the present study used unpractised (novice) subjects with similar levels of caffeine consumptions and personality characteristics, the visual search/detection domain of information processing is shown to be insensitive to the effects of caffeine. This supports the general view that caffeine does not affect cognition, learning, and memory performance. Also, the non‐significant three‐way interaction of drug, automaticity, and task difficulty would therefore suggest that caffeine does not affect resource capacity. Of note is that knowledge of drug administration assessments (drug guessing) was sensitive to the effects of caffeine in the automatic condition and not in the non‐automatic condition, suggesting that the effects of caffeine are task‐dependent. In contrast, the expected sensitivity of mood assessments to caffeine's effects was not shown. Since caffeine is shown to be a ‘weak’ stimulant, given its commonly known non‐significant effects on mental performance, caffeine‐administered subjects may lack sufficient external cues to allow them to perceive and report correctly that they were given caffeine.
Clinical data and animal studies on adaptive receptor changes occurring in depression and after antidepressive treatment: A hypothesis of antidepressive action
Authors: Płaźnik A. , Kostowski W.
Published: December 2004

The clinical and animal studies on the effects of antidepressant treatments on receptor‐related changes in the functioning of central neurotransmitter systems, are reviewed. The great variability in individual clinical responses make it impossible to formulate one coherent hypothesis about adaptive receptor changes occurring in human beings. Nevertheless, it is concluded that neuroadaptive responses found in the catecholaminergic systems (dopaminergic and adrenergic alpha‐1 receptors) might be important as the underlying mechanism for therapeutic efficacy in depression of antidepressant drugs (AD) and electroconvulsive shock treatment (ECS). The animal studies conducted in our laboratory over the last decade provide evidence for the existence of limbic neurotransmitter modulatory mechanism of action of AD and ECS. It is suggested that at least in the limbic areas (i.e. in the hippocampus and nucleus accumbens, the main structures of the mesolimbic system), AD and ECS produce bidirectional effects. On the one hand they were found to reduce ‘inhibitory’ signals mediated through serotonergic, GABA‐ergic and alpha‐2 adrenergic receptors while on the other hand they enhanced ‘excitatory’ central processes mediated via the dopaminergic and adrenergic alpha‐1 receptors. Confirmation of this hypothesis was obtained from behavioral experiments (locomotor and exploratory activity), consisting of microinjections of selective receptor agonists and antagonists into the hippocampus and nucleus accumbens, following the chronic administration of different AD's and ECS. We propose, therefore, that the mechanism of action of antidepressant therapies should be considered from the anatomical and receptor viewpoint, the crucial element being the ‘tuning’ of the signals within the limbic areas. The consequence of this mechanism is an enhancement of these processes which can be defined as ‘activatory’, in terms of their mood elevating effects. The final effect of antidepressant therapy emerges as a result of transmitter interactions and disinhibitory processes. The ‘limbic modulatory neurotransmitter mechanism’ is thus suggested to be responsible for the effect of antidepressant treatment.
Performance effects of drugs of abuse: A methodological survey
Authors: Foltin Richard W. , Evans Suzette M.
Published: December 2004

This paper provides a methodological survey of research of 1253 experiments on the acute effects of drugs used for non‐medical purposes on human performance. 305 different tasks were tested, but only 118 tasks were used in more than two experiments. While the majority of experiments did have control conditions and measured drug effects at more than one time point after drug administration, they varied widely on other protocol details: (1) subject populations, (2) training on the tasks prior to drug administration, and (3) number of active test doses that were tested. Administration of stimulants either had no effect, or improved performance. In contrast, administration of marijuana, alcohol, or benzodiazepines had no effect, or impaired performance. In order to maximize comparability and utility, future protocols should use control groups, train subjects prior to participation, test more than one drug dose, and test performance before, and several times after, drug administration. A greater range of subject populations should also be studied. Finally, task standardization including type of instructions to subjects, duration of performance testing, feedback to subjects, motivational conditions, and inclusion of a benchmark task should also be used to enhance comparisons across studies.
The effects of brofaromine alone and in conjunction with alcohol on cognitive function, psychomotor performance, mood and sleep in healthy volunteers
Authors: Kerr J. S. , Fairweather D. B. , Hindmarch I.
Published: December 2004

Brofaromine is a novel antidepressant that functions by the inhibition of the A form of monoamine oxidase (MAO). This inhibition is reversible, making brofaromine both pharmacologically and structurally different from most of the currently available MAO inhibitors. The drug has been shown to be clinically effective and to have significantly fewer problems than other MAO inhibitors in terms of hepatic toxicity and interaction with tyramine and coadministered tricyclic antidepressants. The present experiment was designed to assess the behavioural toxicity of the drug. Seventeen normal volunteers received brofaromine 50 mg or 75 mg, amitriptyline 50 mg or placebo with and without alcohol in a double blind eight‐way crossover study. A psychometric test battery was administered at 3, 6 and 12 h post‐dose. The results show that brofaromine had little or no effect on the measures employed, compared to placebo. The amitriptyline verum (with and without alcohol) however lowered critical flicker fusion threshold compared to placebo at all test points, increased reaction time, increased tracking error, and slowed memory scanning. It is concluded that, in volunteers, acute doses of brofaromine are free from disruptive effects on cognitive function and psychomotor performance, in contrast to both amitriptyline and alcohol which showed debilitating effects on most of the measures employed.
Normal neuropathological findings after neuroleptic malignant syndrome
Authors: Koponen Hannu J. , Lepola Ulla , Leinonen Esa , Paljärvi Leo
Published: December 2004

Neuroleptic malignant syndrome (NMS) is a rare, life‐threatening complication of antipsychotic drug treatment. Its pathophysiology is controversial, and the same is true for the findings in post‐mortem studies on central nervous system pathology. In this report we present a patient who died two and a half months after suffering NMS. The findings in a thorough neuropathological examination were normal suggesting that the postulated dopamine receptor blockade in NMS is not associated with a structural central nervous system damage.
Cognitive functions in chronic schizophrenic patients with tardive dyskinesia
Authors: Soni Som. D. , Neill David , Sheffield Brian
Published: December 2004

Two groups of chronic stable schizophrenics matched on several parameters but differing only with respect to presence or absence of tardive dyskinesia (TD) were compared for cognitive function using the Bexley Maudsley Automated Psychological Screen and the Category Sorting Test. The results showed that although all schizophrenics performed poorly on the psychometric tests in this inventory, there was no difference between the two groups for any of the cognitive functions tested. Stepwise multiple regression analysis performed on patients with TD revealed that age and extrapyramidal symptom (EPS) score were the only variables consistently associated with oro‐facial TD where as EPS correlated inversely with TD of limbs and trunk. Our results did not support the hypothesis that tardive dyskinesia in schizophrenic patients is associated with additional or specific cognitive dysfunction.
State‐dependent retrieval and midazolam
Authors: File Sandra E. , Goodall Elizabeth M. , Mabbutt P. S. , Harris A. , Skelly Ann M.
Published: December 2004

This experiment investigated the phenomenon of state‐dependent retrieval with midazolam by comparing performance after midazolam + placebo with that after reversal with the benzodiazepine antagonist flumazenil, in tests of explicit and semantic memory and judgements of recency. The subjects completed analogue rating scales and psychomotor tests to provide measures of sedation. Midazolam (0.05 mg/kg) impaired recall and recognition of pictures and performance in the digit‐symbol substitution task. There were no significant state‐dependent effects with this dose. Midazolam (0.075 mg/kg) impaired recall and recognition of words and pictures and recognition of coloured slides of complex scenes. There were significant state‐dependent effects on all the recognition tests, i.e. the group tested after reversal with flumazenil (0.5 mg) performed worse than that tested after placebo. Midazolam (0.075 mg/kg) also impaired recency judgements and performance in the number cancellation and digit‐symbol substitution tests, but there were no state‐dependent effects in these tests. To determine whether subjects had insight into their memory impairments, for each task they were asked to rate on an analogue scale whether they thought their memory would be ‘better or worse than usual’. Those tested with midazolam (0.075 mg/kg) showed no insight into their memory impairments and there were negative correlations between actual and estimated performance. However those reversed with flumazenil were aware their memory was worse than usual and had positive correlations between actual and estimated performance, similar to those shown by subjects tested undrugged.
Effects of discontinuation of individual antiepileptic drugs on mood
Authors: Kendrick Anna M. , Duncan John S. , Trimble Michael R.
Published: December 2004

Forty‐four patients undergoing withdrawal of phenytoin, carbamazepine or sodium valproate and 21 patients on stable medication were assessed using standardised, objective ratings of mood, notably the Mood Adjective Checklist and the Middlesex Hospital Questionnaire. The study followed a prospective, double‐blind, placebo‐controlled design. Patients' mood was assessed before and after drug withdrawal with an additional assessment being made four weeks after the completion of withdrawal. The number of seizures, serum anticonvulsant levels and EEGs were assessed at the same time as the mood assessments. In addition, the potential influence of life events on mood was monitored.

Anxiety, as measured by the Middlesex Hospital Questionnaire, increased on withdrawal of carbamazepine. This change was not related to seizure rate. Withdrawal of phenytoin or sodium valproate did not appear to have an impact on mood. Concomitant changes in serial EEGs are discussed in relation to the changes in mood.
A double‐blind, placebo‐controlled study of the effects of eptastigmine on scopolamine‐induced cognitive deficits in healthy male subjects
Authors: Lines C. R. , Ambrose J. H. , Heald A. , Traub M.
Published: December 2004

This double‐blind, placebo‐controlled, crossover study examined the effects of two single doses of eptastigmine, a novel cholinesterase inhibitor, on scopolamine‐induced cognitive deficits in 24 healthy male volunteers. Each subject received the following treatment sequences, separated by at least 1 week, in a randomly assigned order:

0h
2h

PlaXcebo (p.o.) Placebo
(i.m.)

Placebo (p.o.)
Scopolamine (0.4 mg i.m.)

Eptastigmine (20 mg p.o.)
Scopolamine (0.4 mg i.m.)

Eptastigmine (32 mg p.o.)
Scopolamine (0.4 mg i.m.)

A battery of computerized cognitive tests, lasting approximately 1 h, were administered 30 min after the i.m. scopolamine/placebo injection. Subjective visual analogue scale ratings were undertaken immediately prior to the first treatment (eptastigmine/placebo) and on completion of the cognitive test battery. In addition, blood samples were taken immediately following the subjective ratings, and at 2 h (prior to the scopolamine/placebo injection), to determine peripheral acetylcholinesterase and butyrylcholinesterase activity.

Scopolamine‐induced deficits were found on a number of the cognitive tests and subjective ratings. Neither dose of eptastigmine significantly reversed or diminished these impairments. The two doses of eptastigmine produced the anticipated mean levels of red blood cell acetylcholinesterase inhibition (20 mg = 23 per cent; 32 mg = 37 per cent).
Pilot study of flesinoxan, a 5‐HT1A agonist, in major depression: Effects on sleep REM latency and body temperature
Authors: Ansseau Marc , Pitchot William , Moreno Antonio Gonzalez , Wauthy Jacques , Papart Patrick
Published: December 2004

Flesinoxan is a highly potent and selective 5‐HT1A full agonist, active in several models of depression. In this pilot open study, flesinoxan (4 mg/d) was administered orally for 4 weeks in 16 major depressive, mostly treatment‐resistant inpatients exhibiting a score of at least 19 on the Hamilton depression sale. Weekly ratings included Hamilton depression scale, Montgomery and Asberg depression scale (MADRS), and Clinical Global Impressions (CGI). Results showed considerable improvement in depressive symptomatology with mean MADRS scores (SD) dropping from 35.7 (10–40) to 13.0 (11.9) and CGI‐illness severity from 5.69 (1.14) to 2.73 (1.62) after 4 weeks of treatment. Moreover, 13 patients were classified as much or very much improved on the CGI‐global improvement. The tolerance of flesinoxan was excellent, with only four patients exhibiting side‐effects. In contrast to acute studies with 5HT1A agonists, flesinoxan induced no significant decrease in daily oral temperature over the 4‐week period. In eight melancholic patients, the mean REM latency (SD) of respectively 35.6 (15.9) and 40.2 (17.9) min during two baseline nights significantly increased to 51.9 (20.9) min during a double‐blind challenge night with flesinoxan 1 mg as compared to 42.0 (16.1) min with placebo, and to respectively 55.6 (29.9) and 55.6 (30.2) min during the last two treatment nights. All these findings encourage further developments of flesinoxan as a promising antidepressant.
Antidepressant therapy with moclobemide in primary care practice
Authors: Angst J. , Gachoud J.‐P. , Gasser U. E. , Köhler M.
Published: December 2004

A Swiss, open, multicentre clinical study was conducted in collaboration with 176 general practitioners and internists to evaluate the efficacy and tolerability of moclobemide, an antidepressant belonging to a class of novel reversible MAO‐A inhibitors called RIMAs. Six hundred and fifty‐four outpatients satisfying the DSM‐III criteria of major depression were recruited and treated for at least four weeks. Efficacy was assessed with the Hamilton Depression Rating Scale (HDRS) and the Hospital Anxiety and Depression (HAD) self‐rating scale. Subjects were grouped according to depression subtype, history, age and seveerity of depression and were evaluated individually.

The global efficacy was assessed by the HDRS and Clinical Global Impression (CGI). The HDRS‐score was reduced significantly after four weeks of treatment (p < 0.001). Moclobemide was effective in depression associated with anxiety or psychomotor retardation, in neurotic and agitated depression, in recurrent and chronic depression as well as initial depressive episodes, and in both young and old patients. According to the patients' self‐ratings (HAD), moclobemide provided rapid relief of depressive and anxiety symptoms. The drug was well tolerated, as evidenced by the low incidence of side‐effects.
Effects of smoking on cognitive performance and psychophysiological parameters as a function of smoking state
Authors: Hasenfratz M. , Bättig K.
Published: December 2004

Twenty female regular smokers were tested in four sessions while performing a 20‐min rapid information processing task (RIP) twice. According to a 2 × 2 crossover design they were required to abstain from smoking or not on the mornings before the session and allowed to smoke between the two RIP trials. Pre‐session abstinence, as compared with non‐abstinence, showed the expected withdrawal symptoms in terms of decreased cognitive performance, electrocortical and cardiovascular arousal, increased pre‐session anxiety, craving to smoke and ratings of cigarette strength, nausca and dizziness after smoking a cigarette during the session. Smoking during the session, as compared with non‐smoking, on the other hand, showed some beneficial effects in terms of increased cognitive performance electrocortical and cardiovascular arousal. Whereas these effects were antagonistic for most of the assessed parameters, there were also some significant interactions. The increases in processing rate, heart rate and stroke volume and the decreases in finger pulse amplitude, left‐ventricular ejection time and state anxiety due to smoking were greater after preceding abstinence than non‐abstinence. This reflects the great impact of the acute tolerance to nicotine. Finally, no positive effects of smoking on the RIP‐task‐induced physiological stress reactions were found, suggesting that smoking as a coping aid is of only restricted value.
Benzodiazepine associated reversal of the effects of experimental sleep fragmentation
Authors: Roehrs Timothy , Merlotti Lori , Rosenthal Leon , Roth Thomas
Published: December 2004

Thirty‐six healthy young men and women (age 21–35) received 0.00, 0.25, or 0.50 mg triazolam (n = 12 per group) while undergoing experimental sleep fragmentation in which sleep was disrupted by presenting tones to produce brief EEG arousals (without shortening sleep time). The following day subjects' daytime function was assessed using the Multiple Sleep Latency Test and a divided attention performance task. The fragmentation of sleep produced significant disruption of nocturnal sleep and it reduced daytime alertness. Both active drug doses, relative to placebo, reversed the experimentally produced sleep disturbance and they restored daytime alertness.
Paralytic ileus as a prodromal symptom of the neuroleptic malignant syndrome
Authors: Tanaka Osamu , Otani Koichi , Kondo Tsuyoshi , Kaneko Sunao , Fukushima Yutaka
Published: December 2004

A schizophrenic patient receiving neuroleptic treatment developed paralytic ileus followed by the neuroleptic malignant syndrome (NMS). The patient had previously experienced two NMS episodes, one of which was also accompanied by paralytic ileus. It is suggested that paralytic ileus can occur as a prodromal symptom of NMS. Therefore, if this symptom is observed in patients receiving neuroleptic treament, especially those with a past history of NMS, careful attention should be paid to the possible development of NMS.