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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 91 records · Page 5Linked to original sources
PubMed1987

Differential amnesic properties of benzodiazepines: a dose-response comparison of two drugs with similar elimination half-lives.

The effects on memory and psychomotor functions of oxazepam (15, 30 mg) were compared with those of its chlorinated derivative lorazepam (1, 2 mg) and placebo. Forty five volunteers took part in a double-blind, independent groups design. Subjects completed a battery of tests before and 1.5 and 3 h after drug administration. Lorazepam and oxazepam had similar dose-related effects on tests of attention, manual motor speed and recoding skills and all active treatments produced similar levels of subjective sedation. Both drugs caused anterograde impairments of long-term verbal memory and had no effects on short-term verbal span or recency. Neither drug produced retrograde amnesia for material learned before drug administration nor affected retrieval from semantic memory. The high (2 mg) dose of lorazepam positively facilitated recall of pre-drug information. The magnitude of anterograde amnesia produced by the two benzodiazepines was not linearly dose-related in that the two low doses had similar effects whereas the high dose of lorazepam produced impairments many times greater than oxazepam 30 mg. We conclude that drugs with similar half-lives may have similar effects on some cognitive and mood factors but be completely different in terms of amnesic effects. Differing potencies of the two drugs may be a more important factor determining amnesic side-effects.

Adult↗
PubMed1987

Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects.

The purpose of the study was to ascertain whether the new hypnotic, zopiclone, was likely to produce rebound problems after short-term use, in comparison with placebo and a standard hypnotic, temazepam, and whether tapering the dosage lessened any such effects. Ten normal v olunteer subjects were administered 5 treatment sequences, each lasting 4 weeks, using a balanced design, with at least 2 weeks between sequences. The treatment sequences were: (table: see text) Each drug was given at night before retiring to bed. Daily ratings comprised a Sleep Questionnaire, Mood Rating Scales, the Spielberger State Anxiety Inventory and Bodily Symptom Scales. Both drugs improved quality of sleep but their discontinuation was followed by some worsening which was postponed but not avoided by halving the dosage for a week. Speed of, and feeling on, awakening showed discontinuation effects with temazepam but not with zopiclone. Zopiclone was associated with feelings of being troubled, tense, antagonistic and bored whereas temazepam produced drowsiness, clumsiness, dreaminess and sadness. Some increase in these ratings was noted after stopping temazepam and these were less after having the dosage. Zopiclone was associated with minimal such effects. For bodily symptoms, zopiclone produced some headache, a metallic taste, and some blurring of vision; temazepam induced nausea, memory impairment and pins and needles. Withdrawal effects on bodily symptom ratings were inconsistent and not affected by tapering off the dose. In conclusion, the administration of zopiclone tends to be associated with some dysphoric effects, temazepam with sedation. Rebound effects are minimal with zopiclone and reducing the dosage gradually does not seem necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

A follow-up study of patients treated for benzodiazepine dependence.

By interviewing and administering questionnaires to 63 patients one to five years after treatment for benzodiazepine dependence the long-term success rate was examined together with factors associated with outcome. Fifty-four per cent of patients had permanently withdrawn from medication at follow-up. Most of those who were successful continued to experience psychiatric symptoms after discharge. Significantly more women than men managed to withdraw from medication. Outcome was not related to previous benzodiazepine regimen, psychiatric history or experiences of withdrawal. It is argued that psychological adjuncts should be included in the treatment of benzodiazepine dependence in order to prevent relapse.

Adult↗
PubMed1987

Clinical pharmacology of benzodiazepines.

The benzodiazepines are the most widely used anxiolytic drugs. Their pharmacokinetic properties differ widely. Side effects are usually mild but dependence can supervene after long-term administration, even if normal therapeutic doses are not exceeded. Careful monitoring of use is essential.

Benzodiazepines↗
PubMed1987

Recent experience with trazodone.

Trazodone is an atypical antidepressant with additional anxiolytic effects. Recent European experience with trazodone is reviewed with respect to antidepressant efficacy, side effects (particularly anticholinergic), anxiolytic actions, cardiotoxicity, overdosage, and use in the elderly. From the data presented in this paper it is concluded that trazodone is effective both as an antidepressant and as an anxiolytic agent, with few side effects and low cardiotoxicity. It is safer than tricyclic antidepressant agents in overdosage and better tolerated in the elderly patient.

Clinical Trials as Topic↗
PubMed1987

A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms.

Buspirone is a new antianxiety compound of a totally new type which may avoid the dependence problems of its predecessors. This study was designed to evaluate any possible cross-tolerance to the benzodiazepines. Twenty-four outpatients on long-term therapeutic dose benzodiazepine treatment, who wished to discontinue treatment, were allocated randomly to placebo substitution or buspirone substitution and then withdrawal over a total of 10 weeks. Assessments were made at weekly intervals. Of the 24 patients entered into the trial, 13 received buspirone and 11 placebo. Only five of the buspirone and six of the placebo patients successfully completed withdrawal. Some anxiolytic action of buspirone was detected, but it was insufficient to materially assist the withdrawal. No evidence was found that buspirone was cross-tolerant to the benzodiazepines. It was concluded that buspirone does not help benzodiazepine withdrawal and does not suppress benzodiazepine withdrawal symptoms.

Adult↗
PubMed1987

A comparison of buspirone, diazepam, and placebo in patients with chronic anxiety states.

Buspirone is an antianxiety compound that has been extensively evaluated in clinical trials: it has proved superior to placebo and comparable to diazepam in the treatment of patients with generalized anxiety disorder. In this study, 33 outpatients with generalized anxiety disorder were entered into a crossover study of 3 weeks each of placebo, buspirone 10 to 30 mg daily, and diazepam 10 to 30 mg daily. Psychiatrist and patient ratings were made, together with psychological tests and EEG and skin conductance measures before and after each treatment. Of the nine dropouts, six were on buspirone at the time of dropout. For the remaining 24 patients, the mean daily doses attained of buspirone and diazepam were both 20 mg. On most clinical ratings diazepam was superior to buspirone and placebo, which did not differ. Diazepam produced minor psychomotor changes and the expected major effects on the EEG. Buspirone was without effect. Side effects on buspirone were mainly nausea and giddiness and on diazepam, drowsiness. The lack of efficacy of buspirone is discussed in terms of the previous benzodiazepine exposure--23/24 patients had had previous exposure and only 10 were able to tolerate a pretrial placebo washout period. The implications are considerable for the introduction of any new antianxiety agent not cross-tolerant with the benzodiazepines into a chronically anxious group of patients with previous long-term benzodiazepine therapy.

Adult↗
PubMed1987

Long-term anxiolytic therapy: the issue of drug withdrawal.

Although widespread use has confirmed their efficacy as anxiolytic agents, the benzodiazepine drugs are indicated only for short-term or intermittent therapy at as low a therapeutic dose as possible because of their liability for causing dependence or abuse. When first introduced, benzodiazepine drugs appeared to be therapeutically equal or superior to barbiturate agents, while causing fewer side effects, being safer in overdose, and producing fewer dependence and abuse problems. Although benzodiazepine drugs have become the most commonly prescribed anxiolytic agents, evidence has emerged that their use in long-term therapy can cause severe withdrawal problems, even when relatively low doses are used or when the drug is discontinued gradually. Based on results from both animal models and clinical investigations, buspirone appears to be as effective in treating anxiety as the benzodiazepine drugs while causing fewer withdrawal problems. Data suggest no appreciable propensity to cause physical dependence or abuse associated with buspirone therapy. The drug demonstrates no cross-tolerance with either the barbiturate agents or the benzodiazepine drugs and seems to be a dysphoriant at high doses rather than a euphoriant. Although buspirone seems to be an appropriate drug for patients requiring longer-term anxiolytic therapy, careful monitoring for withdrawal problems and other adverse side effects is essential as buspirone is introduced to successive markets.

Anti-Anxiety Agents↗
PubMed1986

Management of benzodiazepine dependence.

Dependence is a recognized problem in a significant number of patients taking therapeutic doses of benzodiazepines. A characteristic withdrawal syndrome has been described. These patients are best managed as outpatients with gradual dosage reduction over 4-12 weeks. Pharmacological adjuncts such as propranolol and non-benzodiazepine hypnotics are useful for certain specific symptoms, but so far no single substance has proved useful in attenuating the majority of symptoms. Psychological and social support should be maximized, but here again no single technique has been shown to be more than moderately successful. The best treatment is thoughtful prescribing ab initio.

Barbiturates↗
PubMed1986

Effects of repeated doses of fluvoxamine, mianserin and placebo on memory and measures of sedation.

The effects on memory and learning of fluvoxamine 50 mg twice a day were compared with those of mianserin 20 mg twice a day and placebo, each given for 8 days in a double-blind cross-over design to nine healthy human volunteers. At least 1 week was left between the 8-day courses of drugs. Subjects were given a learning task (three trial recall of categorisable word lists) before and 3.5 h after a morning dose on day 1 and before their morning dose on day 8. Delayed recall was assessed on days 1, 4 and 8. Fluvoxamine had no effect on memory performance. Mianserin reduced learning and recall after a single dose but had no effect on day 8 of treatment. The single dose of mianserin had no retrograde effect on memory, affected primacy and middle position items but not recency in the serial position curve, and was seen in reduced inter-trial subjective organisation of recall. Subjects' performance on the first trial of the memory task correlated significantly with their performance on a simple reaction time task, with finger tapping speeds and with their subjective ratings of alertness. It was concluded that the impairments of memory produced by one dose of mianserin are partially by-products of the sedative effects of the drug. Tolerance to both memory impairments and sedative effects built up over the 8-day treatment of mianserin.

Adult↗
PubMed1986

The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects.

Citalopram, a selective 5-HT uptake inhibitor with antidepressant properties, was assessed in three studies in 12 healthy subjects using a battery of EEG, psychological, subjective and symptomatic measures. Study A involved the administration of citalopram, 20 mg and 40 mg, amitriptyline 50 mg and placebo in single dose using a balanced cross-over design. The test battery was applied before, and 1 and 3 h after each drug. Citalopram decreased slow-wave EEG activity whereas amitriptyline increased power in most EEG wavebands. Citalopram increased tapping rate and symbol copying whereas amitriptyline impaired these and other psychomotor tasks. Subjectively, amitriptyline was much more sedative than citalopram and produced more complaints of dry mouth. Study B comprised the administration of citalopram in the usual clinical dose of 40 mg, amitriptyline in the low clinical dose of 75 mg and placebo, each given for 9 nights using a balanced cross-over design. The test battery was applied on the first morning (pre-drug) and on the morning after the last nightly dose. None of the physiological tests showed any drug effects. Subjectively, citalopram was associated with feelings of shaking, nausea, loss of appetite and physical tiredness; amitriptyline produced feelings of shaking, nausea, loss of appetite, dryness of mouth, irritability, dizziness and indigestion; in general, amitriptyline effects were more marked than those of citalopram. Plasma samples were taken on the last day and plasma concentrations of both drugs and their metabolites were found to be in the expected range for the regimens used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The psychopharmacological effects of repeated doses of fluvoxamine, mianserin and placebo in healthy human subjects.

The psychopharmacological effects of fluvoxamine, 50 mg twice a day, were compared with those of mianserin, 20 mg twice a day, and placebo, each given for 8 days in a double-blind crossover design to 9 healthy human volunteers. At least one week was left between the 8-day courses of drugs. Testing was carried out before and 3 h after taking the morning dose on Days 1 (pre-drug), 4, and 8, and comprised EEG, cognitive and psychomotor tasks, and self-ratings of mood and bodily symptoms. Fluvoxamine had no effect on any of the EEG wavebands, but mianserin increased voltages in the slow wavebands as compared with placebo. This effect was particularly pronounced on Days 4 and 8. Mianserin significantly decreased critical flicker fusion frequency and speed of reaction time, and slowed down tapping rate; digit symbol substitution and symbol copying test performances were also impaired by mianserin. These effects were most marked after the first dose and had lessened somewhat later in the week. Symbol copying was the only task impaired by fluvoxamine as compared with placebo. Mianserin caused drowsiness after the first dose but this effect declined by Day 8. By contrast, fluvoxamine induced feelings of anxiety, sweatiness, trembling, nausea, loss of appetite, restlessness, muscle tension, irritability, tiredness, headache, and dizziness; these effects were most evident in the middle of the week and relatively reduced at the end of the week. Mianserin produced a few of these effects but they tended to be maximal on Day 1 or 4 and then to wear off.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects.

Ro 15-1788 is an imidazodiazepine which was initially described as a pure benzodiazepine antagonist lacking in intrinsic actions. Although recent animal work has shown the drug to have differing intrinsic actions depending on the dose, the majority of studies on human subjects conclude that it is a pure antagonist of benzodiazepines. Two oral doses of Ro 15-1788 (30 mg and 100 mg) were compared with 5 mg diazepam and placebo in their intrinsic effects on a range of psychophysiological, performance and subjective measures in 12 healthy adult subjects. At both these doses Ro 15-1788 showed a mixture of agonist (benzodiazepine-like) effects and other non-benzodiazepine-like effects on the variables measured. Although there was no clear-cut dose-response relationship, the results suggested a predominance of benzodiazepine-like effects at the higher dose on physiological measures whilst the lower dose was observed to have greater effects on a number of behavioural and subjective dimensions. The subjective changes were the opposite of those normally found for benzodiazepines.

Adult↗
PubMed1986

A method to elicit aggressive feelings and behaviour via provocation.

A technique is described which elicits hostility via provocation in a competitive reaction time task incorporating a predetermined failure rate of 50%. When the subject loses he is exposed to a white noise which increases in intensity through the experiment. When he wins he is able to administer one of 8 levels of noise to his opponent. Heart rate and skin conductance level and fluctuations were monitored throughout the experiment. Self-ratings of mood, aggression and anxiety were completed both pre and post task. It was found that the task elicited hostility which could be measured behaviourally, physiologically and emotionally.

Adult↗