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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 55 records · Page 3Linked to original sources
PubMed1993

The effects of nefazodone, imipramine and placebo, alone and combined with alcohol, in normal subjects.

Nefazodone (200 mg, 400 mg/day) imipramine (150 mg/day) and placebo were administered to 12 normal, healthy volunteer subjects for a period of 8 days each. A measured dose of alcohol was consumed with the drug on day 8. A battery of physiological, psychomotor, cognitive and subjective tests was carried out before drug administration and 2 h after drug administration on days 1, 7, and 8. Nefazodone had little effect on heart rate and blood pressure whereas imipramine increased both heart rate and diastolic blood pressure. Nefazodone 400 mg impaired the critical flicker fusion threshold. Dose-dependent improvements in psychomotor performance (Gibson Spiral Maze) and complex memory performance (learning, pursuit rotor, and visual working memory) were produced by nefazodone while imipramine administration impaired performance on these tasks. Subjective changes in alertness and bodily symptoms were produced by all active compounds. While nefazodone failed to potentiate the sedative-hypnotic (depressant) effects of alcohol, imipramine tended to enhance them for psychomotor performance, memory assessments, and some subjective ratings. Thus, nefazodone, particularly at lower dose levels, causes less disruption of human performance than imipramine. This effect probably reflects the lack of anticholinergic activity of nefazodone. Also, nefazodone failed to potentiate the depressant effects of alcohol, perhaps because of its minimal alpha-blockade.

Adolescent↗
PubMed1993

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

Chronic normal-dose benzodiazepine users requesting drug withdrawal were allocated to substitution with either the new anxiolytic alpidem (n = 13) or placebo (n = 12). During the first 2 weeks of the tapering programme, the dose of benzodiazepine was kept constant; for the next 2 weeks it was halved and half-dose alpidem (25 mg twice daily) or placebo substituted; for weeks 5 and 6, the benzodiazepine was discontinued and full-dose alpidem or placebo given; next alpidem or placebo were tapered to half-dose and then finally discontinued. Regular anxiety and tranquillizer withdrawal ratings were made. Nine of 12 patients given placebo withdrew successfully compared with four of 13 alpidem-treated patients. Anxiety and other symptom levels increased in the alpidem but not the placebo patients. It was concluded that alpidem is not helpful in helping patients withdrawing from a benzodiazepine withdrawal perhaps because of partial agonist properties. These actions may imply a lesser propensity to induce dependence on long-term use.

Adult↗
PubMed1992

Anxiogenic effects of caffeine in patients with anxiety disorders.

The effects on measures of anxiety from two doses of oral caffeine (250 and 500 mg) and placebo were compared in 12 patients with generalized anxiety disorder (GAD), 12 patients with panic disorder, and 12 normal subjects. Caffeine produced significantly less decrease in electroencephalographic alpha wave activity, greater decrease in N1-P2 auditory evoked potential amplitude, and greater increased in skin conductance level, systolic and diastolic blood pressure, critical fusion flicker frequency, and self-ratings of anxiety and sweating in patients with GAD than in normal patients. Patients with panic disorder showed different reactivity than normal patients did with respect to electroencephalographic alpha waves, N2 latency, N2-P2 auditory evoked potential amplitude, and physical tiredness but were less reactive than patients with GAD on several variables. It is concluded that patients with GAD are abnormally sensitive to caffeine and that the data support the view that panic disorder is a separable disorder from GAD.

Alpha Rhythm↗
PubMed1992

The interactions of ethanol with single and repeated doses of suriclone and diazepam on physiological and psychomotor functions in normal subjects.

The effects of diazepam (5 mg t.i.d.), suriclone (0.2 and 0.4 mg t.i.d.) and placebo (t.i.d.) were assessed in 12 normal, healthy volunteer subjects after a single dose and after treatment for a period of 8 days. A battery of physiological, psychomotor and subjective tests was administered on days 1 and 8 both before and after drug and after a measured dose of ethanol. The effects of diazepam on the EEG were characteristic of benzodiazepines-a decrease in the slow frequency wave-bands, an increase in fast frequency wave-band and diminished evoked response amplitude. Suriclone had similar effects on fast frequency activity and evoked response amplitude but, in contrast to diazepam, also increased the slow frequency wave-bands after 7 days treatment. Some improvements in performance were seen with suriclone on critical flicker fusion, tapping speed, spiral maze and digit cancellation. In contrast, suriclone impaired performance to a greater extent than diazepam on digit symbol substitution and symbol copying. Body sway was also enhanced by suriclone to a greater extent than diazepam. Subjective ratings for mood and adverse-effects showed few differences between suriclone or diazepam. However, suriclone caused greater gastro-intestinal disturbances than diazepam, especially after ethanol, and subjects rated themselves as more antagonistic and more irritable on suriclone. Ratings for calmness suggested that in contrast to diazepam, suriclone had no anxiolytic effect. Several of the parameters tested showed a build up of effect with diazepam over the treatment period which was not seen with suriclone. It is suggested that this difference may be due to differences in elimination rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Rebound insomnia and newer hypnotics.

The prescription of hypnotics, mostly benzodiazepines, continues at a high level. One problem with their use is rebound insomnia: upon discontinuation sleep worsens compared with pretreatment levels. Factors influencing rebound include the type of subject, the duration of action of the hypnotic, the dosage and perhaps duration of treatment. The detection of rebound requires both sleep-laboratory and clinical studies with night-by-night analyses of individual patient data. This review concentrates on the newer compounds, (quazepam and zolpidem) which act selectively on subtypes of benzodiazepine receptors or bind atypically (zopiclone). It concludes that present evidence, while limited, is consistent with claims of less rebound potential than older benzodiazepine hypnotics of equivalent duration of action. Nevertheless, further rigorous studies are essential before these claims can be totally accepted.

Humans↗
PubMed1992

Alpidem and lorazepam in the treatment of patients with anxiety disorders: comparison of physiological and psychological effects.

The physiologcal and psychological effects of the novel imidazo-pyridine alpidem were compared with those of the benzodiazepine lorazepam in the context of a clinical trial. Twenty-three psychiatric out-patients with generalised anxiety disorder received alpidem (mean dose 112.5 mg daily) or lorazepam (mean 3.5 mg daily) in doses adjusted to clinical need under double-blind conditions. A battery of tests was performed before and after four weeks treatment. Anxiety scores improved very significantly in both groups with no subjective sedation nor other particular side-effects noted in either group. However, lorazepam reduced the EEG averaged evoked response and produced significant impairment in the reaction time and memory tests whereas alpidem had no such effects. Alpidem therefore shows promise as an effective anxiolytic devoid of the adverse psychomotor and cognitive effects often associated with the benzodiazepines.

Adult↗
PubMed1992

Rapid tranquillisation. A survey of emergency prescribing in a general psychiatric hospital.

Rapid tranquillisation--giving a psychotropic to control behavioural disturbances--is common in medical practice, yet few surveys describe its use in psychiatric populations. Over five months, 102 incidents, involving 60 patients, were retrospectively surveyed. Patients most often involved were young white men. The commonest diagnosis was affective disorder (manic phase) (39%) followed by schizophrenia (33%). Fifteen patients were involved in 57% of the incidents. The majority of incidents involved injury to people or damage to property. The most frequently used drugs were diazepam and haloperidol, alone or in combination. Droperidol, chlorpromazine, sodium amytal and paraldehyde were rarely used. Diazepam alone or in combination with haloperidol delivered intravenously was most rapidly effective and was associated with greatest staff satisfaction. Serious side-effects were rare.

Aggression↗
PubMed1991

The effects of repeated doses of clomipramine and alprazolam on physiological, psychomotor and cognitive functions in normal subjects.

The effects of a 10 day administration of clomipramine (25-50 mg t.i.d.), alprazolam (0.25-0.75 mg t.i.d.) and placebo were assessed in normal volunteers in a double-blind cross-over study. A battery of physiological, psychomotor and cognitive tests was administered both before and 3 h after drug on days 1, 5 and 10. The effects of alprazolam on EEG and evoked potentials were characteristic of benzodiazepines; clomipramine had little effect. In contrast, reaction speed was markedly slowed by clomipramine but little affected by alprazolam. Neither drug produced any accumulation of effect on a verbal recall task but neither did tolerance develop to the acute impairments produced by active treatments. Alprazolam produced an increase in levels of forgetting, especially on day 5. Subjective ratings for mood and bodily symptoms were adversely affected by clomipramine but little altered by alprazolam. It is suggested that some of the differences between drug treatments may be due to differences in the speed of onset of tolerance.

Adult↗
PubMed1991

Does tolerance develop to the sedative and amnesic effects of antidepressants? A comparison of amitriptyline, trazodone and placebo.

The psychomotor, sedative and memory effects of a sedative, anticholinergic antidepressant (amitriptyline), a sedative antidepressant (trazodone) and placebo were compared in a double-blind, cross-over study with 12 healthy volunteers. Amitriptyline (37.5 mg) and trazodone (100 mg) were administered for the first 7 days of treatment and in double-dosage for the next 7 days of treatment. Subjects completed a battery of tests before and 2 h after drug administration on days 1, 8 and 14. Over the 2 weeks of treatment, there was no accumulation of effects but subjects experienced marked sedation and psychomotor impairments following a daily dose of both active drugs. Although both amitriptyline and trazodone produced impairments on memory tasks, the effect of amitriptyline was significantly greater and may reflect its anticholinergic action over and above global sedative effects. Tolerance to the effects of amitriptyline built up differentially over measures of sedation, psychomotor function and memory.

Adult↗
PubMed1991

Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood.

The effects on memory, psychomotor functions and mood of intramuscular scopolamine (0.3 mg, 0.6 mg) were compared with those of oral lorazepam (2 mg) and placebo. Thirty-six volunteers took part in a double-blind, independent groups design. Subjects completed a battery of tests 1 and 3 h after drug administration. Both doses of scopolamine produced levels of sedation comparable to that produced by lorazepam. The time course of effects of scopolamine and lorazepam differed but the pattern of psychomotor impairments and amnestic effects produced was very similar. In terms of mood, lorazepam had an anxiolytic effect whereas scopolamine increased ratings of anxiety. Levels of sedation, indexed by either subjective ratings or motor retardation (tapping speed), were related more to psychomotor performance than to performance on memory tasks. The results suggest that benzodiazepines and scopolamine have similar amnestic and sedative effects and as such may not offer distinct models of memory dysfunction.

Adult↗
PubMed1991

History of benzodiazepine dependence.

The benzodiazepines were developed in the 1950s, some introduced in the 1960s, and many more since then. Pharmacologically, they are sedative/hypnotics akin to alcohol, chloral, the barbiturates, and meprobamate. All have been widely used both within and outside the licit medical context. Usage of benzodiazepines increased dramatically during the 1960s and early 1970s; tranquilizer but not hypnotic usage has since declined. Both abuse and misuse were documented early, but the incidence was deemed low in view of the widespread prescription. Normal-dose physical dependence was first suspected in the early 1970s but it was not until the early 1980s that scientific evidence was adduced to establish its reality and frequency. Further studies have revealed the complex nature of the withdrawal syndrome. A reaction has set in against these drugs, with attempts to limit them to short-term use.

Anti-Anxiety Agents↗
PubMed1991

Benzodiazepine problems.

Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.

Anti-Anxiety Agents↗
PubMed1991

Can buspirone induce rebound, dependence or abuse?

Buspirone is a newer anxiolytic which differs chemically and pharmacologically from the benzodiazepines. The question as to whether buspirone can induce rebound, dependence, or abuse can be examined through a variety of clinical and control studies, as well as animal studies, together with meticulous follow-up of adverse reports. It is concluded that, on present evidence, the short-term use of buspirone is unlikely to be followed by rebound or long-term use through dependence; nor is abuse likely to be a problem.

Anxiety Disorders↗
PubMed1991

Does alcohol modify responses to reward in a competitive task?

Alcohol in two doses (0.75g/kg and 0.25/kg) and a placebo were administered to three matched groups of subjects. Subjective ratings and breath alcohol levels were completed pre-intake and at 30 min intervals up to 2 hr after intake. At 1 hr post-intake, the subjects took part in a competitive task with increasing rewards during which cardiac and electrodermal activity were monitored. Alcohol had very little effect. It did not affect the level of reward administered nor the physiological parameters measured. The only mood effect was sedation. There was no evidence of tension reduction or response disinhibition.

Adult↗
PubMed1990

Drug development optimization--benzodiazepines.

The benzodiazepines are among the most widely-used of drugs. Sedative effects are common but tend to lessen after a few days, although cognitive effects may persist. Car accidents and falls in the elderly are the most serious practical consequences. On discontinuation, a variety of syndromes are encountered, including relapse, rebound, and withdrawal. Anxiety disorders tend to be remitting and relapsing rather than chronic. Withdrawal follows a characteristic course and symptom pattern, perceptual hypersensitivity being common and distressing. The syndrome is worse after stopping shorter-acting than longer-acting benzodiazepines. Benzodiazepines are prescribed for many different mental and physical conditions, sometimes inappropriately. Chronic use for twelve months or more ranges from 0.5% of the adult population in Sweden through 1.8% in the U.S.A., 3.1% in the U.K., and 6.8% in Belgium. Benzodiazepines differ with respect to elimination half-life and potency. High-potency compounds may be particularly likely to induce sedation, memory disturbance and perhaps dependence. Partial agonists may be less of a problem in these respects. Newer compounds include benzodiazepines with selectivity on one or other of the putative subclasses of receptor, partial inverse agonists and antagonists, compounds acting near the benzodiazepine complex, and new drugs, such as buspirone, believed to act primarily on 5-HT pathways.

Benzodiazepines↗