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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 127 records · Page 7Linked to original sources
PubMed1983

Correlations among measures of response to benzodiazepines in man.

A retrospective analysis of five studies using benzodiazepines and one using a benzodiazepine-like drug, zopiclone, and involving 61 subjects in toto was carried out. All used a placebo control and all acute studies incorporated pre-treatment values as well. Eight variables which have previously been shown to be sensitive to benzodiazepine action and which covered a range of physiological, psychological and subjective measures were chosen. Within-subject correlations between drug minus placebo values for these variables were computed to examine relationships between the measures while the subjects were taking benzodiazepines. It was found that closely related measures within system were significantly correlated but other correlations were sparse. However under limited conditions, i.e., several doses of one drug in the same subjects as in the zopiclone study, a consistent pattern of effects was shown across measures, resulting in half of the possible correlations showing statistical significance. A similar pattern was shown in patients after 2-4 weeks treatment with benzodiazepines.

Anti-Anxiety Agents↗
PubMed1983

A double-blind study to establish the residual effects of zopiclone on performance in healthy volunteers.

A double-blind study was designed to establish the residual effects of zopiclone on performance in healthy volunteers. 10 healthy male volunteers aged 22-45 years (mean age 27.4 years) were included in this study. 6 of the volunteers were cigar/cigarette smokers and were asked to smoke as little as possible on the study days. The subjects were randomly allocated to a balanced design in which each subject received single oral doses of placebo, 2.5-, 5-, 7.5- and 10-mg tablets of zopiclone under double-blind conditions. A battery of tests were performed 10 and 13 h after overnight ingestion of the drug. The tests comprised: EEG, auditory reaction time, tapping rate, digit symbol substitution test, symbol copying test, mood rating scales, side effects rating scales, and subjective assessments of sleep and performance. Zopiclone is shown to have useful hypnotic properties but residual effects are detectable using EEG and psychological tests both 10 and 13 h after ingestion. The 10-mg dose significantly impairs performance the next day; the 5-mg dose is almost devoid of residual psychomotor effects but is only marginally effective in hastening onset of sleep and does not improve sleep quality. The 7.5-mg dose has definite effects on sleep and limited residual effects the next day. No significant side effects were reported. In this study, using single doses in healthy subjects, the best balance between wanted hypnotic effects and unwanted residual effects the next day was provided by the 7.5-mg dose of zopiclone. It is recommended that further studies with repeated doses in healthy volunteer subjects and in insomniac patients use the 7.5-mg dose as the reference point.

Adult↗
PubMed1983

Rational use of anxiolytic/sedative drugs.

The benzodiazepines are the most effective, safest, and most widely used antianxiety drugs. As a class of drugs, there are few major differences between the various benzodiazepine derivatives. The main distinguishing features are different plasma half-lives and the presence or absence of pharmacologically active metabolites. Plasma half-lives vary considerably, from 2 to 3 hours to more than 100 hours. All benzodiazepines are equally effective in the short term management of anxiety and insomnia, and their classification into 'anxiolytics' and 'hypnotics' is not justified. There are numerous other indications for benzodiazepine use, such as muscle spasm in osteoarthritic conditions, and acute alcohol withdrawal, but the benzodiazepines have no antidepressive or analgesic effects. While there is no good evidence for their long term efficacy in the treatment of anxiety and insomnia, the benzodiazepines are more effective and safer than their main predecessors, the barbiturates. Some of the benzodiazepines, particularly those with long plasma half-lives which are commonly used as hypnotics, have a prolonged duration of action and cause marked 'hang-over' effects. Alcohol enhances the effects of these drugs, and thus can also increase their side effects. Adversely effects such as oversedation, tremor, ataxia and confusion are much more common in elderly patients. Ever since the benzodiazepines were first marketed 20 years ago their use has increased rapidly, and it is now estimated that between 12 and 16% of the adult population in developed countries use tranquillisers at some time each year. However, their overall use has probably diminished somewhat in the last few years. Although their indications are very common, it is possible that some of this extensive usage may be the result of dependence. Until recently, published reports of such dependence were comparatively few. However, withdrawal symptoms have now been demonstrated in a substantial proportion of patients on long term, normal dose benzodiazepine treatment. The abstinence syndrome usually lasts for 8 to 10 days, and is characterised by insomnia, anxiety, loss of appetite and bodyweight, tremor, perspiration, and a host of perceptual disturbances. More serious developments such as epileptic fits and psychosis are probably infrequent during withdrawal from therapeutic doses. The overall incidence of benzodiazepine dependence remains unknown.

Anti-Anxiety Agents↗
PubMed1983

Dependence on benzodiazepines.

Psychotropic drugs are widely prescribed and tend to be used on a long-term basis. The barbiturates are known to induce tolerance and dependence, with a well-defined and often severe withdrawal syndrome from high doses. By contrast, the benzodiazepines are infrequently associated with tolerance and dependence at high doses. Recent work, however, has suggested that a definite withdrawal syndrome can supervene on discontinuation of long-term normal doses of benzodiazepines. In view of the widespread and chronic use of the benzodiazepines, this may represent a major problem. The theoretical implications of such normal-dose dependence are discussed.

Adult↗
PubMed1983

The psychophysiology of anxiety.

Psychophysiology is the study of physiological measures in the human for information about behavioral concomitants. Measures used include heart-rate, blood-pressure, palmar sweating (skin conductance), salivation, pupil size, electromyogram, respiration, electroencephalogram and averaged evoked response. States of anxiety are accompanied by physiological changes which can be regarded as high "arousal". Such measures are useful as monitors of emotional change, both during the induction and alleviation of anxiety. Finally, psychophysiology provides some insights into the complex nature of anxiety and its relationship to brain mechanisms.

Anti-Anxiety Agents↗
PubMed1983

Combined use of tricyclic antidepressants and monoamine oxidase inhibitors.

Combined treatment with tricyclic antidepressants and MAO inhibitors has been an area of some controversy. The efficacy of the combination approach is not established; the only controlled trail showed trimipramine alone to be superior to an MAOI alone and to the combination of trimipramine with an MAOI in treating depressed outpatients not selected for a history of treatment refractoriness. The safety of the combination varies according to the specific drugs used; tranylcypromine and clomipramine are not recommended, and recent pharmacologic studies suggest that specific serotonin reuptake inhibitors are dangerous in combination with MAOIs. Further controlled clinical studies are clearly needed before combined therapy can be recommended for routine clinical use.

Adult↗
PubMed1983

The problems of safety and compliance with conventional antidepressant drugs.

The incidence of unwanted effects with tricyclic antidepressants usually ranges between 15% and 30%. Adverse effects particularly involve the autonomic nervous system and the cardiovascular system, and sedation is common. Tricyclics interact with many other drugs including antihypertensive agents, monoamine oxidase inhibitors (MAOIs), anticholinergic drugs, antihistamines and sedatives (especially alcohol). Overdoses of tricyclics are hazardous, producing respiratory and cardiac depression, fits and coma. Compliance is poor with tricyclic antidepressants, mainly due to the side-effects, particularly sedation and dry mouth, and to a failure in doctor-patient communication. The range of pharmacological effects, wanted and unwanted, reflects the relative lack of selectivity of these drugs: more selective drugs should be advantageous in the treatment of depression.

Antidepressive Agents, Tricyclic↗
PubMed1983

Behavior and anxiety: physiologic mechanisms.

The distinction between "normal" and clinical anxiety and the theories put forth to explain the etiology and nature of both experiences are described. Research directed toward elucidation of the psycho- and neurophysiology of anxiety is reviewed; two major neurophysiologic models based on animal studies are presented. None of the various models proposed to date adequately explains human anxiety. Further clinical studies on the symptoms and natural history of anxiety are suggested.

Animals↗
PubMed1982

A comparison of the psychotropic profiles of tofisopam and diazepam.

Twelve normal subjects were tested on a number of measures both before and 1,3 and 5 h after 10 mg diazepam, 100 and 200 mg tofisopam and a placebo. The measures included self-ratings of mood, bodily symptoms, hostility and sleep, the electroencephalogram (EEG), reaction time, tapping, digit symbol substitution, the symbol copying test, and plasma levels. Diazepam showed a clear profile of action, producing EEG changes, pronounced sedation and psychological impairment. The last two effects were maximal at 1 h and had worn off by 5 h. The EEG was recorded at 3 h only. Tofisopam in no way resembled diazepam. It produced no changes on the EEG or psychological tests and a very mild stimulant effect was apparent on the ratings. While diazepam was easily detectable in the blood, tofisopam did not bind to benzodiazepine receptors.

Adult↗
PubMed1982

Residual effects of repeated doses of 0.5 and 1 mg flunitrazepam.

9 normal subjects were tested on a large battery of tests the morning after a hypnotic dose of flunitrazepam (0.5 mg and 1 mg) and a placebo. Each drug was given for 8 nights and assessments were made 10 and 13 h later on days 1, 4 and 8. Self-ratings of sleep were made every morning. The tests comprised mood and bodily symptom self-ratings, taping rate, visual reaction time, symbol copying and substitution tests, critical flicker fusion threshold, digit span and cancellation test. The EEG was recorded under eyes open and eyes closed conditions and analysed using broad waveband filters. Subjectively, the 0.5 mg dose was associated with increased alertness, contentment and calmness, the 1 mg dose with minimal decrease in alertness and contentment. Sleep onset was accelerated by flunitrazepam initially but effects on quality of sleep were not major due to subject selection. The 1 mg dose occasionally impaired performance on tapping, symbol copying and substitution and critical flicker fusion. The 0.5 mg dose marginally impaired symbol substitution and improved symbol copying. The EEG showed definite dose-related effects which tended to increase over the 8 nights of ingestion of the drug. It is concluded that whereas the 1 mg dose may sometimes be associated with definite residual effects the next day, the 0.5 mg dose possesses positive qualities in producing useful subjective effects the next day without appreciable impairment of psychological performance.

Adult↗
PubMed1982

Psychological effects of buspirone.

Chief among the drawbacks of the benzodiazepines is the risk of a withdrawal syndrome when the drugs are discontinued after prolonged periods of use, even at therapeutic dosages. Another disadvantage, common to sedative, tranquilizer, and hypnotic drugs, is psychological impairment or inappropriate behavioral effects. The psychological effects and impairments associated with benzodiazepines will be presented as a standard against which to assess new drugs. Results of objective tests confirmed that buspirone showed similar effects to diazepam in terms of self-rated mental sedation, but less physical sedation. Buspirone had little physiologic effect and produced less impairment in psychological performance.

Adult↗
PubMed1982

A double-blind study to establish the residual effects of zopiclone on performance in healthy volunteers.

A double-blind study was designed to establish the residual effects of zopiclone on performance in healthy volunteers. 10 healthy male volunteers aged 22-45 years (mean age 27.4 years) were included in this study. 6 of the volunteers were cigar/cigarette smokers and were asked to smoke as little as possible on the study days. The subjects were randomly allocated to a balanced design in which each subject received single oral doses of placebo, 2.5-, 5-, 7.5- and 10-mg tablets of zopiclone under double-blind conditions. A battery of tests were performed 10 and 13 h after overnight ingestion of the drug. The tests comprised: EEG, auditory reaction time, tapping rate, digit symbol substitution test, symbol copying test, mood rating scales, side effects rating scales, and subjective assessments of sleep and performance. Zopiclone is shown to have useful hypnotic properties but residual effects are detectable using EEG and psychological tests both 10 and 13 h after ingestion. The 10-mg dose significantly impairs performance the next day; the 5-mg dose is almost devoid of residual psychomotor effects but is only marginally effective in hastening onset of sleep and does not improve sleep quality. The 7.5-mg dose has definite effects on sleep and limited residual effects the next day. No significant side effects were reported. In this study, using single doses in healthy subjects, the best balance between wanted hypnotic effects and unwanted residual effects the next day was provided by the 7.5-mg dose of zopiclone. It is recommended that further studies with repeated doses in healthy volunteer subjects and in insomniac patients use the 7.5-mg dose as the reference point.

Adult↗