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Biomedical subjects

H Petursson

Publications and source records attributed to H Petursson.

53 records · Page 3Linked to original sources

Psychometric performance during withdrawal from long-term benzodiazepine treatment.

Twenty-two patients were withdrawn from normal-dose, long-term benzodiazepine treatment and their data compared with those of two control groups. Patients and controls were assessed repeatedly on the Digit Symbol Substitution Test (DSST), Symbol Copying Test (SCT), Cancellation Task (CT), Auditory Reaction Time (RT) and Key Tapping Rate (KTR). A substantial and prolonged practice effect was found on all the tests except RT and KTR. Prior to withdrawal the patients did not show the performance decrement on the CT, RT and KTR customarily associated with the initial phases of benzodiazepine therapy. A rebound performance increment was observed on KTR during the withdrawal. Patients demonstrated impaired performance on tasks requiring the combined use of sensory and fine motor skills.

Adult↗

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↗

Monoamine metabolism during chronic benzodiazepine treatment and withdrawal.

Long-term normal-dose benzodiazepine treatment in seven patients was associated with reduced urinary excretion of MOPEG (4-hydroxy-3-methoxy-phenylglycol). Following the discontinuation of the drugs a characteristic withdrawal reaction occurred, with an increase towards normal values of the MOPEG excretion levels and changes in the excretion of 5-HIAA (5-hydroxyindoleacetic acid). No significant changes in the 24-hr urinary excretion of free cortisol or HMMA (3-methoxy-hydroxy-mandelic acid) were detected.

Adult↗

Withdrawal from long-term benzodiazepine treatment.

Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety.

Anti-Anxiety Agents↗

Urinary MAO inhibitor in psychiatric illness.

Normal human urine contains an endogenous monoamine oxidase inhibitor. We have now investigated its activity in urine samples from psychiatric patients in various diagnostic categories. Significantly higher values were observed in alcoholics recently withdrawn from ethanol, compared with controls. Inhibitory activity was not specifically related to primary affective disorders. Inhibitor output may be positively related to certain symptom clusters rather than to disease entities (i.e. alcohol withdrawal, agitation, and hyperkinesis). Significantly lower inhibitor output was also found in a small group of patients with chronic schizophrenia.

Adolescent↗

Benzodiazepine derivatives--side effects and dangers.

The benzodiazepines are generally safe and effective drugs with usually only minor side effects, dose-related sedation being the most common. A range of paradoxical effects can occur of which release of aggressive and hostile feelings has excited most attention. These responses are idiosyncratic however, as most patients report decrease of such feelings while taking benzodiazepines. Dependence on benzodiazepines with escalation of dosage and/or social abuse is uncommon set against their widespread use. Recently though, evidence has accumulated that patients on normal doses for prolonged periods can commonly experience withdrawal symptoms, often unpleasant and even severe. These drugs should be reserved for patients suffering from defined clinical anxiety syndromes and not used indiscriminately in patients with normal stress responses.

Aggression↗

Diethylpropion and paranoid psychosis.

The case of a 36-year old woman who developed a paranoid psychosis while abusing diethylpropion is reported. It is suggested that the newer appetite-suppressing drugs have a bigger abuse potential than eas previously thought and may therefore be a hazard for a minority of susceptible subjects. The need to test separately for diethylpropion in cases of suspected drug-induced psychosis is emphasized.

Adult↗

Lithium treatment of a patient with periodic catatonia.

This case report describes successful lithium treatment in a patient with long-standing periodic catatonia. Various medical treatments had been tried with meager results. Since 1955, a number of phenothiazines had been tried, also with little improvement. The institution of lithium treatment in 1964 caused a dramatic improvement in the patient's condition. For 9 years the patient remained totally asymptomatic. Lithium treatment was terminated in 1975 because of lithium intoxication with a diabetes insipidus-like syndrome. The patient then became psychotic again and has since experienced periodic phases similar to the previous illness. The diagnostic validity of the case is discussed, and some possible explanations of the favourable response to lithium are mentioned briefly.

Catatonia↗

Molecular genetic evidence for heterogeneity in manic depression.

Manic depression is a severe cyclic mental illness that can be unipolar or bipolar and has a lifetime risk of approximately 7 per 1,000 in most populations. Families with multiple cases of manic depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission. Psychoactive antidepressant and stimulant drugs that help to ameliorate depression and mania are thought to act by affecting catecholamine neurotransmitter systems such as adrenaline, noradrenaline and dopamine, amongst others. Mutations affecting the tyrosine hydroxylase (TH) gene, which encodes the rate-limiting enzyme for the synthesis of these three neurotransmitters, might therefore be responsible for causing the manic depressive phenotype. We have studied three Icelandic kindreds amongst whom it appears that a single autosomal dominant disease allele is segregating. In these families there were 44 cases amongst 73 individuals at risk. Genetic linkage studies were carried out using clones encoding tyrosine hydroxylase the variable portion of the Harvey-ras-1 (HRAS1) locus and the variable region of the insulin gene (INS). All three markers are closely linked on chromosome 11 and were used to observe the segregation of restriction fragment length polymorphisms (RFLPs) in the three affected kindreds. We found no evidence for linkage to these markers in any of the three families. In contrast, Gerhard et al. found linkage between manic depression and HRAS1 in a single large Amish kindred. We conclude that there is genetic heterogeneity of linkage in manic depression. Therefore mutations at different loci are responsible for the manic depressive phenotype in the Amish and in Iceland.

Bipolar Disorder↗

Linkage analysis of manic depression (bipolar affective disorder) in Icelandic and British kindreds using markers on the short arm of chromosome 18.

Attempts were made to follow up results of a previous linkage study which suggested that a locus-modifying susceptibility to bipolar and related unipolar affective disorder might be present in the pericentromeric region of the short arm of chromosome 18. Twenty-three multiply affected pedigrees collected from Iceland and the UK were genotyped using three highly polymorphic microsatellite markers at D18S37, D18S40 and D18S44 which span the region implicated. Lod score analyses under the assumption of heterogeneity and non-parametric linkage analyses were performed. The total lod scores obtained were strongly negative, and analysis allowing for heterogeneity did not suggest that any subgroup of the families was linked. Model-free linkage analysis using extended relative pair analysis and MFLINK also failed to detect any evidence for linkage. Our study provides no support for the presence of a locus-modifying genetic susceptibility to bipolar affective disorder in the pericentromeric region of chromosome 18q11. Further analyses in independent samples should help to reveal whether our negative results are due to locus heterogeneity or whether the original results were false-positive.

Alleles↗