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Biomedical subjects

M Lader

Publications and source records attributed to M Lader.

At least 19 recordsLinked to original sources
PubMed2005

The effect of escitalopram on sleep problems in depressed patients.

The results from three 8-week escitalopram studies in major depressive disorder are presented with respect to efficacy and the effect on sleep quality, both in the full population and the subpopulation of patients with sleep problems at baseline. Analysis of pooled data from these randomized, double-blind, placebo-controlled, studies in which citalopram was the active reference, showed a significant improvement for escitalopram-treated patients (n = 52.0) in the Montgomery-Asberg depression rating scale (MADRS) item 4 ('reduced sleep') scores at weeks 6 and 8 compared with placebo (n=398; p < 0.01) and at weeks 4, 6 and 8 (n = 403; p < 0.05) compared with citalopram.Escitalopram-treated patients with sleep problems (MADRS item 4 score > or = 4; n = 254) at baseline showed a statistically significant improvement in mean MADRS item 4 scores at weeks 4, 6 and 8 compared with patients treated with placebo (n = 191; p < 0.05) or citalopram (n = 193; p < 0.01). These patients also showed a statistically significant (p < 0.05) and clinically relevant improvement in MADRS total score after escitalopram treatment compared with citalopram at weeks 1, 4, 6 and 8 (observed cases) and endpoint (-2.45; last observation carried forward [LOCF]). Statistical significance in favour of escitalopram versus placebo treatment was found at all visits, including endpoint (-4.2; LOCF).Thus, these post-hoc analyses suggest that escitalopram has a significant beneficial effect compared with placebo or citalopram in reducing sleep disturbance in patients suffering from major depressive disorder. The effect of escitalopram in improving 'reduced sleep' scores was clearly seen in patients with more severe sleep disturbance at baseline. A further prospective study is needed to establish this useful clinical effect in insomniac depressives.

Adolescent↗
PubMed2000

Social phobia: diagnosis and epidemiology, neurobiology and pharmacology, comorbidity and treatment.

Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure. The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs.

Adrenergic beta-Antagonists↗
PubMed1999

The influences of age and caffeine on psychomotor and cognitive function.

RATIONALE: The response to caffeine is affected by a number of factors, including age. Older subjects may be more sensitive to the objective effects than younger but report fewer subjective effects. OBJECTIVE: This study assessed the influence of age on the effects of caffeine on a variety of psychomotor, cognitive and subjective tests. METHODS: Forty-eight healthy subjects, male and female, were recruited, 24 in the age range 20-25 and 24 in the range 50-65 years. All subjects were regular moderate caffeine drinkers and were not withdrawn from caffeine before entry to the study. A double-blind parallel group design was used with two groups of 12 subjects in each age range. One group in each age range received placebo and the other 250 mg caffeine B.P. A range of tests was used to assess psychomotor, cognitive and subjective functioning before and 1 h post-treatment. RESULTS: Before treatment, young subjects generally performed better than older on psychomotor and cognitive tests. On the subjective tests, however, older subjects rated themselves as more alert and less tired than the younger ones. After placebo, performance and alertness improved in the younger group but declined in the older. After caffeine there were improvements in psychomotor performance and cognitive functioning in both groups, particularly in offsetting declining performance over time in the older subjects. It also produced subjective improvements in alertness. One factor to emerge was that on most assessments older subjects were better earlier in the day whereas in younger subjects performance did not show the same magnitude of decline throughout the day. CONCLUSIONS: Caffeine induced small but significant improvements in vigilance and psychomotor performance.

Adult↗
PubMed1999

The influence of drugs upon testimony.

A wide range of drugs (medicines) are used currently, many of which are designed to affect brain function. Others do so as a side-effect. The effects depend on how the body deals with the drug (pharmacokinetics) and how the drug affects the body, including the brain (pharmacodynamics). An extensive range of effects on the brain and psychological functioning can ensue, including effects on intellectual functioning, dexterity, memory, learning and subjective effects. Individual factors are important and can profoundly influence both the type and extent of drug effects. Relevant drugs can be divided into: 1. Those prescribed primarily to treat psychiatric disorders. These include sleeping tablets, tranquillizers, antidepressants and antipsychotics. 2. Those used to treat neurological disorders that have psychological side-effects. Examples are anticonvulsants and anti-parkinsonian drugs. 3. Those used to treat non-nervous disorders that may have psychological side-effects. 4. Illicit drugs used in the non-medical context by drug addicts. Drug-induced states that can influence testimony are mainly sedation, disinhibition, paradoxical reactions and alterations in memory. A list of pointers was given in this paper with respect to practical considerations in assessing the possible effects of drugs on testimony.

Cognition↗
PubMed1999

Brain uptake of iomazenil in cirrhotic patients: a single photon emission tomography study.

Brain uptake of 123I-iomazenil was studied in seven cirrhotic patients and eight normal controls using single photon emission computerized tomography. The highest concentration of the ligand was found in the occipital cortex, which corresponds to the brain region with the highest concentration of benzodiazepine receptors. The peak uptake was delayed in patients across all brain regions. The uptake in occipital cortex was higher in low albumin cirrhotics. Patients with low albumin also presented a more delayed peak uptake in occipital cortex and a higher volume of distribution of iomazenil in plasma, compared to patients with normal albumin levels and controls. The changes in brain uptake (delayed peak uptake and increased maximal uptake in occipital cortex) appears to reflect changes in the pharmacokinetics of the ligand, particularly in cirrhotics with low levels of plasma albumin. The curve of brain uptake of the tracer was modelled into a two compartments equation, which seems to provide a practical and reliable method to calculate the slopes of acquisition and decay, time to peak and maximal acquisition.

Adult↗
PubMed1999

Some adverse effects of antipsychotics: prevention and treatment.

Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent.

Antipsychotic Agents↗
PubMed1998

A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder.

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.

Adolescent↗
PubMed1998

The clinical relevance of treating social phobia.

Social phobia is an extreme fear of being scrutinized by others in social situations that often culminates in avoidance of those situations. Studies have demonstrated marked educational, occupational and social disabilities in patients with social phobia. However, many sufferers do not seek help and are not detected when seeking medical advice for other conditions. The advent of a range of effective treatments, in particular the selective serotonin reuptake inhibitors, has substantially improved the prognosis in these sufferers, both symptomatically and in terms of quality of life.

Humans↗
PubMed1998

Pharmacological prevention of relapse.

Relapse is the "return of a disease after partial recovery", and is a major feature of schizophrenia disorder. It can be defined in terms of need for change in treatment, including rehospitalization or crisis intervention, the re-emergence of florid psychotic features, or gross social decompensation. Relapse is best viewed as continuum of severity rather than as discrete "attacks". Factors influencing relapse include major life events and the family constellation. Antipsychotic drugs protect against the latter but not the former, and relapse may be mediated by non-specific arousal mechanisms. The efficacy of drug treatment in postponing rather than preventing relapse is well established. The interval between relapses is prolonged at least two-fold, but in the long run most patients relapse. Unwanted effects of antipsychotic drugs can be a burden to patients, impairing quality of life. In particular, movement disorders and subjective dysphoria may be marked, as may compliance. Of these EPS, tardive dyskinesia is the most serious on long term use. Non-EPS long term effects include weight gain and endocrine changes. Depot medication has advantages over oral medication in the more ill, less compliant patients. Side effects may, however, be more marked. The greatest pain is in improved compliance but the regular supervision of the patient is also helpful. Pharmacokinetic issues are poorly understood. High and mega-dose strategies have been advocated. High doses may be needed in some patients, but megadoses are rarely justified and may be hazardous. Low dose and intermittent therapy have been evaluated but are not as successful as hoped. Some less ill patients may benefit. These schedules depend on the identification of prodromata of relapse which is not always easy, nor are relapses necessarily preceded by prodromata. Newer drugs are being developed rapidly in the search for a safer clozapine, the only antipsychotic with definitely enhanced efficacy. Other drugs which have been re-evaluated include the benzodiazepines. However, the area of greatest priority in research is that of interactions, particularly potentiation, between drug and non-drug treatments.

Antipsychotic Agents↗
PubMed1997

Zopiclone: is there any dependence and abuse potential?

Both published and unpublished data concerning the rebound, withdrawal, dependence and abuse potential of zopiclone have been reviewed. As expected for an hypnotic drug of about 5 h elimination half-life, rebound has occasionally been detected but is substantially less frequent than with equivalent benzodiazepines. Tolerance to zopiclone does not occur regularly and cross-tolerance to the benzodiazepines may help in a regimen to withdraw from the latter drugs. Dependence on long-term use, as shown by either a characteristic withdrawal syndrome or by psychological craving, is rare considering the world-wide extent of usage. Abuse (addictive non-medical use) is documented but is also rare, in comparison with the widely abused benzodiazepines. It is concluded that zopiclone has substantial advantages over the benzodiazepines in terms of dependence and abuse potential.

Azabicyclo Compounds↗
PubMed1995

Encoding, remembering and awareness in lorazepam-induced amnesia.

The effects of lorazepam (1,2 mg) and placebo on encoding, remembering and awareness were assessed in a study with 54 healthy volunteers. All subjects studied stimulus materials in a levels of processing (L-o-p) task. Half the subjects were assessed on an explicit memory task of word recognition and the other half were given an implicit memory task of word-stem completion. Following the implicit task, awareness of retrieval was further investigated by questions and by subjects' recollective experience in recognising the actual words they had completed from stems. L-o-p effects and marked lorazepam-induced impairments were found in the implicit task of word-stem completion although the interaction between L-o-p and drug effects emerged only as a trend in the data. Lorazepam-induced impairments on stem-completion may then be explained at least in part as being due to contamination by explicit retrieval processes, but we cannot rule out the possible role of drug effects on perceptual processes at encoding. Results from responses to "awareness" questions and from analysis of subsequent recollective experience indicated that subjects were not aware of using explicit retrieval during the implicit task. Results also replicated previous findings showing that both lorazepam and L-o-p independently affect performance in an explicit memory task of word recognition. Thus drug-induced deficits at encoding persist regardless of the level at which information is initially processed.

Adult↗
PubMed1995

Differential effects of flumazenil in alcoholic and nonalcoholic cirrhotic patients.

Ligands to the benzodiazepine receptor (BZR) accumulate in hepatic encephalopathy; the benzodiazepine antagonist flumazenil can reverse some manifestations of this condition. This study was designed to explore the effects of flumazenil on cognitive function and anxiety levels in cirrhotic patients without hepatic encephalopathy. Twenty such patients--ten alcoholic, ten nonalcoholics--and ten normal volunteers matched for age and sex were randomly allocated to treatment order (flumazenil or placebo first) in a double-blind cross-over trial. Cognitive function was evaluated with a battery of psychological tests shown previously to be sensitive to the impairment induced by liver disease. Cirrhotic patients performed worse than controls on several tests: digit cancellation, digit symbol substitution, key tapping and Reitan's trail B test. Flumazenil did not reverse these cognitive impairments but it did induce anxiety in nonalcoholic cirrhotics. On one index of memory--delayed word recall--alcoholics performed worse than nonalcoholic cirrhotics. Flumazenil reversed this memory impairment in the alcoholic cirrhotic group. These results suggest that alcohol consumption induces changes at the BZR that are different from changes induced solely by liver impairment.

Adult↗