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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 73 records · Page 4Linked to original sources
PubMed1990

Studies with alpidem in normal volunteers and anxious patients.

Alpidem, an imidazo-pyridine compound, has been evaluated as an anxiolytic in comparison with placebo and lorazepam. In the first of our normal volunteer studies, we compared single doses of alpidem, 25, 50 and 100 mg with lorazepam 2 mg and placebo on a range of cognitive, psychomotor and EEG variables. Lorazepam and the highest (100 mg) dose of alpidem impaired performance on a range of psychomotor tasks, the effects of the benzodiazepine being more severe and more prolonged. No impairment of performance was observed with the 25 and 50 mg doses. In the second study, the focus was on memory functions. Lorazepam, 2 mg, caused anterograde amnesia which was most apparent 1 h post-drug but persisted until 4 h: sedation was marked. By contrast, single doses (25, 50 mg) of alpidem had little effect on either memory or alertness. The third study compared the effects of alpidem (25, 50 mg) and lorazepam (1 mg) with placebo, each given twice-daily for 8 days to normal volunteers. On the final day, a test dose of ethanol was given. Lorazepam impaired many tests of cognitive and psychomotor function, and this impairment was enhanced by ethanol. By contrast, alpidem produced less impairment with less interaction with alcohol. In a fourth, clinical, study, 24 patients with a DSM III primary diagnosis of generalised anxiety disorder were treated, under double blind conditions, with doses adjusted according to clinical need of either alpidem 25-150 mg daily or lorazepam 1-6 mg daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Anxiety Agents↗
PubMed1989

Caffeine abstention in the management of anxiety disorders.

Caffeine toxicity remains a rarely reported condition, which may mimic anxiety disorders. Anxiety disorder patients do not consume toxic amounts of caffeine. However, increased sensitivity to caffeine in these patients has been suggested as contributing to their symptoms. Six cases of anxiety disorder are presented who improved with only caffeine abstention, and remained well for at least a six-month follow-up period.

Adult↗
PubMed1989

The cardiovascular effects of antidepressants.

This monograph comprises a review of the cardiovascular effects of the various types of antidepressant drugs in clinical use. The frequency, severity and clinical importance of these effects are placed in perspective. Most antidepressants can cause changes in blood pressure. Both the tricyclic type (TCA) and the monoamine oxidase inhibitors (MAOIs) can produce postural hypotension which may be dose-limiting. In addition, the MAOIs may be associated with severe hypertension when amine-containing foods or medicines are ingested. It is unlikely that therapeutic doses of any available antidepressant drug could impair cardiac contractility. Typical TCAs can cause abnormalities of cardiac conduction and arrhythmias, but this affects less than 5% of patients, mostly to a clinically insignificant extent. Newer compounds such as lofepramine, mianserin, trazodone and viloxazine seem safer in this respect. Reports of an association between therapeutic use of TCAs and sudden death are far from convincing. Overdosage with the MAOIs, lithium and carbamazepine is dangerous but not common; overdose with a TCA is a major source of morbidity and mortality. Lofepramine, mianserin and trazodone are relatively safe in overdose. The use of various antidepressants in patients with hypertension, cardiac failure, angina pectoris, myocardial infarction, or cardiac arrhythmias is discussed and guidelines suggested for the selection and use of antidepressant medication.

Antidepressive Agents↗
PubMed1989

Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects.

Amitriptyline (up to 75 mg/day), fluoxetine (up to 40 mg/day) and placebo were administered to 12 normal, healthy subjects for a period of 7 days. Subjects received each drug in random order and a minimum of 28 days was left between drug treatments. A battery of physiological, psychomotor and subjective tests was administered before drugs (day 1) and on days 4 and 8. On day 8 a measured dose of alcohol was given and the tests repeated at 1 and 3 h after alcohol. Tests before alcohol showed little effect on physiological or psychomotor activity either between drugs or between drugs and placebo. Subjective ratings did show some differences between drugs and in general amitriptyline was tolerated less well than fluoxetine. There were few differences between drugs after alcohol but with some measures the interaction with amitriptyline was subjective rather than additive or potentiating. This reflected the already substantial effects of amitriptyline alone.

Amitriptyline↗
PubMed1988

Long-term treatment of anxiety: benefits and drawbacks.

Anxiety disorders are common conditions, often chronic, occurring in the general population with a prevalence of about 3%. Long-term use of tranquilizers varies from 0.5% of the total adult population in Sweden and 1.3% in Denmark to 3.1% in Great Britain and 5% in France. This use is tending to become more and more long-term. Long-term efficacy of benzodiazepine medication has not been established. Adverse effects include psychomotor and cognitive impairment, especially in the elderly; some, but not all, effects show tolerance. Some impairment can be demonstrated even after years of use. Rebound and withdrawal reactions after long-term use are common. Practical guidelines to minimize long-term use are suggested.

Anti-Anxiety Agents↗
PubMed1988

Antidepressants and human memory: an investigation of four drugs with different sedative and anticholinergic profiles.

The effects on memory and psychomotor functions of four antidepressants which differ in sedative and anticholinergic properties were assessed. Amitriptyline (37.5, 70 mg), trazodone (100, 200 mg) viloxazine (100, 200 mg), protriptyline (10, 20 mg) or placebo were administered in a double blind, independent groups design in which 90 subjects participated. Subjects completed a battery of tests before and 2 and 4 h after drug administration. The different antidepressants produced different patterns of effects across tasks. The relatively non-sedating compounds viloxazine and protriptyline produced very similar profiles and did not impair psychomotor or memory functions. In contrast, the two more sedative antidepressants produced global impairments on test of attention, manual motor speed, recording skills and primary memory. Although both amitriptyline and trazodone impaired performance on episodic memory tasks, the effect of amitriptyline was significantly greater and this may reflect specific anticholinergic action over and above global sedative effects.

Adult↗
PubMed1988

Differential effects of oxazepam and lorazepam on aggressive responding.

Two doses of two very similar benzodiazepines (oxazepam 15 and 30 mg: lorazepam 1 and 2 mg) and placebo were compared 4 h post-administration on a competitive reaction time task designed to measure behavioural aggression. Forty-five subjects were assigned randomly to five independent drug groups. Subjective ratings of mood, anxiety and aggression were completed pre- and post-drug and post-task. Oxazepam and lorazepam had very similar subjective effects, but the higher dose of lorazepam increased aggressive responding on the task more than any other treatment. This may be related to the different ceiling efficacies of the two benzodiazepines.

Adult↗
PubMed1988

Clinical pharmacology of non-benzodiazepine anxiolytics.

Non-benzodiazepine anxiolytics can be conveniently divided into those which are not primarily used as anxiolytics, those which pharmacologically but not chemically resemble benzodiazepines, and those which are novel both chemically and pharmacologically. The former include antidepressants, antipsychotic drugs, antihistamines and beta-adrenergic antagonists. The second group comprises a variety of compounds which act on the benzodiazepine/GABA complex and include alpidem and zuriclone. The most important of the non-benzodiazepine anxiolytics is buspirone, which seems to act on 5-HT mechanisms. The field of anxiolytic therapy is changing rapidly. New drugs are being introduced and the use of old ones questioned. It is hoped that drugs will be developed which are not only effective and safe with no sedation, but also with little or no propensity to dependence and abuse.

Anti-Anxiety Agents↗
PubMed1988

A comparative study of the interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects.

1. Twelve normal volunteer subjects were given amitriptyline, fluoxetine and placebo in clinically relevant doses, each for a period of 7 days. A minimum of 28 days intervened between each drug treatment. 2. A battery of physiological, psychomotor and subjective tests was administered before drugs and on days 4 and 8. 3. On day 8 a measured dose of alcohol was given and the tests repeated 1 hour and 3 hours later. 4. Before alcohol, little effect was shown on physiological or psychomotor activity. Subjective ratings indicated that amitriptyline was less-well tolerated than fluoxetine. 5. Significant differences were found for many measures after alcohol but there were few differences with respect to the drugs.

Alcohol Drinking↗
PubMed1988

Cognitive impairment in long-term benzodiazepine users.

In view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in long-term benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function.

Anti-Anxiety Agents↗
PubMed1988

The natural history of tolerance to the benzodiazepines.

Dependence on benzodiazepines following continued use is by now a well-documented clinical phenomenon. Benzodiazepines differ in their dependence potential. The present studies were aimed at examining the possibility that differential rates of tolerance development might account for differences in dependence risk. Four studies are reported. The first three studies concerned normal subjects. The development of tolerance over a fifteen day period was demonstrated for three different benzodiazepines (ketazolam, lorazepam and triazolam) using two paradigms. Tolerance in terms of a reduction in effectiveness of a repeated given dose was most notable for the benzodiazepine with a medium elimination half-life (lorazepam) for physiological, behavioural and subjective measures. In the case of the drug with the longest elimination half-life (ketazolam) reduction in effectiveness could only be assumed to be occurring if account was taken of the steady increase in plasma concentrations of active metabolites. For this drug it seemed that the physiological measures were those most likely to demonstrate the development of tolerance. Although triazolam showed few significant drug effects on this paradigm (testing being 12 hours after ingestion of this short half-life benzodiazepine), tolerance was seen to develop on some subjective measures. Using an alternative method of testing tolerance, assessing responses to a diazepam challenge dose, a high degree of tolerance on two-thirds of the measures was observed in subjects when pretreated with the benzodiazepine with the most marked accumulation of active metabolites (ketazolam). The other two drugs also led to tolerance development on a range of measures; this was more marked for lorazepam than triazolam. Blunting of the growth hormone response to diazepam was the most sensitive and reliable method of detecting tolerance to the benzodiazepines. Symptoms on discontinuation of the two weeks' intake of the benzodiazepines were marked for all the drugs but unrelated to either the tolerance induced or the elimination half-life of the particular drug. A further clinical study revealed that tolerance persisted in a group of long-term benzodiazepine users for between four months and two years following complete abstinence from the drug. These patients appeared to be less affected by diazepam in terms of its commonly observed subjective effects, regardless of their original medication. These ex-long-term users of benzodiazepines were, however, more likely to manifest two specific types of effects--immediate 'symptom' reduction and exacerbation of 'withdrawal symptoms' over the subsequent week.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers.

Quazepam 15 mg, triazolam 0.25 mg and placebo were administered to 12 healthy volunteers. Each drug was given for 14 nights using a balanced design with at least 28 days between drug administrations. A test battery of physiological, psychological and subjective measures was administered on the mornings of days 1, 8, 14, 15 and 22 of the drug and post-drug periods. Seven days prior to and on days 1 to 28 of the drug and post-drug periods, sleep and self evaluation questionnaires were completed. Quazepam was associated with definite EEG effects, an unexpected improvement in simple motor performance and an increase in several bodily symptoms and ratings of sedation. Triazolam-impaired performance and also increased ratings of bodily symptoms and sedation. Two symptom increases with triazolam--metallic taste and touch sensitivity--might reflect day-time rebound. Sleep quality was improved by both drugs. There was little evidence of tolerance to drug effects on EEG or psychomotor tests. However tolerance was seen to the bodily symptoms and mood ratings. Rebound after drug discontinuation was not convincingly detected.

Adult↗
PubMed1988

A comparative study of the interaction of alcohol with alpidem, lorazepam and placebo in normal subjects.

Twelve healthy volunteers took part in a double-blind, cross-over comparison of the effects of lorazepam and alpidem on a battery of physiological, psychomotor and subjective tests before and after alcohol. Each subject received each treatment for 8 days and alcohol was given on day 8. Tests were carried out on days 1 and 4 and on day 8 before and after alcohol. Before alcohol the effects of alpidem on most tests were generally similar, but considerably less marked than those seen with lorazepam. There were some interesting differences between the two drugs in the effects on EEG and memory. In line with the effects seen with other anxiolytic drugs, lorazepam decreased the amplitude of auditory evoked potential. In contrast, alpidem was associated with an increase or a significantly smaller decrease. This suggests that there is no attenuation of input or central processing of the auditory stimuli. Both lorazepam and the higher dose of alpidem (50 mg) reduced the number of words recalled but the lower dose of alpidem (25 mg) had significantly less effect on both immediate and delayed recall. These differences persisted after alcohol. On most of the tests the depressant effects of the drug before alcohol were enhanced after alcohol. However, the depressant effects of alcohol combined with active drug were in general no greater than those with alcohol with placebo, suggesting some degree of cross-tolerance.

Affect↗
PubMed1988

Psychotropic effects of repeated doses of enalapril, propranolol and atenolol in normal subjects.

1 Enalapril 20 mg, propranolol 160 mg, atenolol 50 mg and placebo each were given once a day for 8 days to 12 normal volunteers, using a Latin-square design and double-blind procedures. A battery of tests was applied before, 2 and 4 h after the dose on day 1 and 8. 2 EEG effects were detected on day 8 with propranolol but not consistently after atenolol or enalapril. 3 Reaction-time, symbol copying and memory were impaired with propranolol; only memory was marginally affected by atenolol. Enalapril impaired memory but improved tapping ability. 4 Subjectively, propranolol was associated with drowsiness, enalapril with calmness and perhaps contentedness. Ratings of headache were increased with enalapril. 5 It is concluded that the apparent beneficial subjective effects of enalapril in clinical practice are attributable partly to intrinsic central effects but mainly to the contrast with beta-adrenoceptor blockers such as propranolol.

Adult↗
PubMed1988

Beta-adrenoceptor antagonists in neuropsychiatry: an update.

Although beta-adrenoceptor antagonists such as propranolol have been used in neuropsychiatry for more than 20 years, their indications, extent of efficacy, and place in therapy remain unclear. In this overview, which concentrates on the recent literature, four indications for use of the drugs are reviewed, with particular reference to efficacy, mode of action, and clinical utility. The indications are anxiety disorders, including performance anxiety; schizophrenia; aggressive behavior; and akathisia. The author concludes that beta-blockers are useful in some forms of anxiety disorder, perhaps those characterized by somatic symptoms and by performance anxiety, and that akathisia seems to be responsive to those drugs. However, the use of high doses of beta-blockers in schizophrenia remains unestablished, and insufficient data are available with respect to their use in aggressive behavior.

Adrenergic beta-Antagonists↗
PubMed1987

Assessing the potential for buspirone dependence or abuse and effects of its withdrawal.

Benzodiazepine anxiolytics are known to pose risks associated with drug dependence, abuse, and withdrawal symptoms. Recently, a new antianxiety agent, buspirone, was introduced in the United States. Buspirone appears to lack abuse liability and does not lead to drug dependence or withdrawal symptoms. This article reviews the results of animal and clinical studies in which the potential for buspirone dependence or abuse and the effects of its withdrawal were assessed.

Animals↗