摘要:

There is very strong evidence in the literature indicating that the presence of subthreshold depressive symptoms is not a benign clinical condition. At least 5 separate investigational groups, including our own, have confirmed that the presence of depressive symptomology not reaching the diagnostic threshold for a DSM-III-R mood disorder diagnosis is correlated with social dysfunction, work impairment and absenteeism, and the potential risk of future episodes of major depression.We have labelled this condition ‘subsyndromal symptomatic depression (SSD)’. A secondary analysis of the National Institute of Mental Health Epidemiological Catchment Area (ECA) Programme database has demonstrated that SSD has a 1-year prevalence of approximately 8% in the general population. The majority of those with SSD were female (approximately 63%) and they presented with a clinical symptom picture that closely resembled that of major depression. However, it was notable that the feature of 14 days of dysphoria/anhedonia, which is a required criterion for a mood disorder diagnosis in the DSM-III-R system, was absent from these patients. It was also noted that patients with SSD more frequently received social welfare and disability benefits than did the general population without depressive symptoms.We have concluded that SSD does represent a significant clinical problem that is not covered by any DSM-III, DSM-III-R or DSM-IV mood disorder diagnosis. Furthermore, this disorder is of considerable importance in public health. An ongoing clinical trial is investigating the efficacy of fluoxetine in SSD.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Antisense oligodeoxynucleotides (ODN) are short (15 to 30 bases) molecules of synthetic single-stranded DNA, complementary to strategically chosen sequences within a target messenger RNA (mRNA).Theoretical considerations and evidence obtained in tissue culture systems have long suggested the usefulness of this class of compounds for blocking the expression of specific gene products. However, antisense ODN had limitations that were likely to reduce their application outside the limited field of cellularin vitrostudies. These limitations include problems of cellular uptake andin vivostability, and high cost of synthesis.The automation of ODN synthesis has dramatically reduced the costs of production. This has led to a rapidly growing number of recent reports that have suggested potential uses for these agents. Emerging applications include their use as novel pharmacological tools in animal studies of brain systems thought to be involved in the pathophysiology of psychiatric and neurological disorders. While there are many obstacles to be overcome before antisense ODN can be considered as therapeutic agents, suggested future applications include the treatment of ischaemic brain damage, schizophrenia, anxiety and drug abuse.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

A number of drugs are available for the treatment of the symptoms of Parkinson's disease. Because monoamine oxidase B (MAO-B) inhibitors may have a neuroprotective action, starting treatment ofde novopatients with these agents may be the best approach. If this therapy is not sufficient to improve symptoms, addition of a levodopa preparation combined with a peripheral dopa decarboxylase inhibitor is the next treatment choice. Treatment can also be started with levodopa, a dopamine agonist, amantadine or an anticholinergic agent. When the treatment is started with a drug other than levodopa, levodopa should be added if the response to that drug is not satisfactory. Daily levodopa dosage should be titrated carefully according to the severity of the disease and the degree of patient satisfaction with this therapy.Successful long term drug treatment of Parkinson's disease requires meticulous management of various problems that may arise from therapy. Among these, levodopa-related motor fluctuations are the most frequent and important problem.Many approaches are now available to reduce the severity and frequency of motor fluctuations, such as the use of controlled release levodopa formulations, concomitant use of a dopamine agonist and/or a MAO-B inhibitor, frequent administration of levodopa, and administration of a protein redistribution diet. Although still at the stage of preliminary clinical investigation, catechol-O-methyltransferase inhibitors appear to have promise for reducing the severity and incidence of levodopa-induced motor fluctuations. On-off fluctuations to levodopa are still difficult to treat satisfactorily.Clozapine may suppress levodopa-induced hallucinations and delusions, without significant worsening of Parkinsonism. A mild degree of drug-related dyskinesias usually does not require special treatment. For more severe dyskinesias 2 approaches can be taken. First, a reduction of the maintenance dose of levodopa until the severity of dyskinesias becomes mild enough to be tolerated. Secondly, the concomitant use of a selective dopamine D2receptor antagonist, such as tiapride, if a reduction of levodopa dosage worsens Parkinsonism. However, tiapride may partially block the anti-Parkinsonian effects of levodopa.The most common adverse effects of other anti-Parkinsonian drugs are gastrointestinal [selegiline (deprenyl), dopamine agonists] and psychiatric (dopamine agonists, amantadine, anticholinergics) effects. Pleuropulmonary change and retroperitoneal fibrosis are rare complications of long term treatment with bromocriptine, and a controlled release formulation of the drug has been developed in an attempt to reduce the overall incidence of adverse effects. Because of their common adverse effects, anticholinergics should be used with care and are contraindicated in patients with narrow angle glaucoma and/or prostate hypertrophy with dysuria.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The somatic symptoms of anxiety cover a wide range of symptoms and diagnostic terms. It is only in recent years that it has been appreciated that many diagnoses formerly given a medical diagnosis (e.g. neurocirculatory asthenia, hyperventilation and irritable bowel syndrome) have a psychological basis that is rooted in anxiety. It is therefore to be expected that treatments that help to reduce any form of anxiety will also relieve somatic symptoms. Thus, standard anti-anxiety drugs, such as the benzodiazepines, other &ggr;-aminobutyric acid (GABA)-facilitatory drugs (e.g. clomethiazole), azaspirones (e.g. buspirone), and antidepressants at standard dosages are all effective in treating the somatic symptoms of anxiety in the short term.However, somatic symptoms tend to be associated with a prolonged course. As such many anti-anxiety drugs are contraindicated for regular treatment because of the risk of dependence associated with long term use. Consequently, other non-drug treatments, such as cognitive therapy and anxiety management, also play an important role in treating somatic symptoms.In addition to general anxiolytic therapies, some specific drugs are available to treat the somatic symptoms of anxiety. These appear to act directly on the organ systems concerned with generating the symptoms. Although there is no evidence that these agents are superior to the general anxiolytic drugs in terms of efficacy, they often have advantages because they have different adverse effect profiles. &bgr;-Adrenoceptor blocking drugs may be particularly helpful for patients who have cardiac symptoms or tremor as their main symptoms, ondansetron and codeine phosphate may reduce the frequency of bowel action in the irritable bowel syndrome, and prochlorperazine and low doses of other antipsychotics may relieve vestibular symptoms associated with anxiety.Because a patient's response to drug treatment can be idiosyncratic and somatic symptoms may be present in many organ systems simultaneously, all these drugs may have a place in management. Guidelines for treatment are suggested on the basis of existing knowledge. However, it is recognised that the extent of this knowledge is at present limited and there is still much to learn.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Tricyclic antidepressants (TCAs) act as antiarrhythmic drugs, with a pharmacology similar to quinidine and other class I antiarrhythmics. This characteristic has until recently been considered an advantage in patients with both depression and arrhythmia. However, developments in cardiology make this situation appear more complicated. Class I antiarrhythmic drugs given to patients with ventricular arrhythmias following myocardial infarction increase rather than decrease mortality. The mechanism behind this increased mortality is not a function of the arrhythmia, but rather of ischaemic heart disease. Because of the similarity of TCAs to class I antiarrhythmic agents, TCAs may carry a similar risk. Recognition of this fact complicates the treatment of depression in patients with ischaemic heart disease.The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRI) have fewer effects on the cardiovascular system than TCAs. Therefore, these agents would appear to be a safer alternative to TCAs in patients with cardiovascular disease. However, their relative efficacy compared with the TCAs is poorly established in the elderly, a patient group that often presents with cardiovascular disease.If a patient with ischaemic heart disease presents with mild to moderate depressive symptoms and a pharmacological treatment for depression is indicated, we would begin with an SSRI. A TCA would only be considered if the patient failed to respond to an adequate trial of the SSRI. In patients with severe, melancholic depression, but mild to moderate ischaemic heart disease, we prefer treatment with a TCA. In patients with severe, melancholic depression and severe ischaemic disease, electroconvulsive therapy (ECT) is a safe alternative to drug treatment.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The treatment of patients with malignant gliomas is palliative and encompasses surgery, radiotherapy and chemotherapy.Outcome measures have demonstrated an improvement in both survival and neurological performance in patients undergoing complete or near complete tumour resection. Following surgery, involved-field radiotherapy (radiotherapy administered to the tumour and to the tissue in a 3cm radius of the tumour) given to a total dose of 60 to 65Gy is administered. Survival is further improved by the coadministration of the chemoradiopotentiator, hydroxycarbamide (hydroxyurea).Adjuvant chemotherapy has been shown to improve survival in approximately one-quarter of patients with glioblastoma multiforme and the majority of patients with anaplastic astrocytoma. However, noa priorimethod exists to predict which patients will benefit from adjuvant chemotherapy. As a consequence, all physiologically young patients with good performance status (or limited neurological disability) are treated with chemotherapy.The best results of adjuvant chemotherapy are achieved with the combination of procarbazine, lomustine (CCNU) and vincristine, so called PCV-3 therapy. Salvage chemotherapy is reserved for patients with tumour progression. The most durable responses (in decreasing order of effectiveness) have been observed with high dose oral procarbazine, cyclophosphamide-vincristine and platinum-containing regimens.In conclusion, chemotherapy has a well defined role in both the adjuvant and salvage settings in patients with malignant gliomas. Although such treatment is palliative, it improves survival in a meaningful proportion of patients.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Lithium is used for the treatment of a number of psychiatric disorders. The effectiveness of the agent for treating mania and for the long term treatment of bipolar and major depressive disorders is well established. It is also of value in bipolar depression, schizoaffective disorder and aggression, and as an augmenting agent in treatment-resistant depression. Lithium has also been tried in numerous other psychiatric and nonpsychiatric conditions.The chemical characteristics of lithium mean that blood concentration monitoring is a simple and useful component of the clinical use of this agent.Adverse effects to lithium are common, but usually tolerable during the course of therapy. Postural tremor sometimes requires treatment with &bgr;-adrenoceptor blockers or primidone. Both hypothyroidism and goitre are common complications that can usually be managed by supplemental thyroid hormone. Cardiovascular adverse effects are uncommon, but occasionally lithium-induced sinus node dysfunction limits treatment. Bodyweight gain can also occur and is difficult to treat. Adverse effects on the kidneys include polyuria and impaired concentrating ability, and, rarely, nephrotic syndrome and reduced glomerular filtration rate (GFR).Lithium intoxication is predominantly a neurotoxicity that is often reversible, but sometimes causes permanent neurological damage or results in death. Haemodialysis is recommended for severe intoxication.Dietary and drug interactions with lithium can be dangerous. Low sodium intake results in reduced renal lithium clearance. Elevated blood lithium concentration can be caused by some diuretics, nonsteroidal anti-inflammatory drugs and angiotensin converting enzyme inhibitors.Despite some imperfections, lithium remains the treatment of choice for bipolar disorder, and is often useful for several other psychiatric conditions.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

There is increasing interest in evaluating the health outcomes and effectiveness of new pharmaceutical treatments for psychiatric disorders, such as depression, anxiety and schizophrenia. There is also increased emphasis on understanding the affect of treatment on patient quality of life.Few comprehensive health-related quality of life (HRQL) studies have been performed to examine social, occupational and functional outcomes in patients with chronic schizophrenia. The most widely used scales include the Social Adjustment Scale, the Quality of Life Scale and the Quality of Life Interview. New scales, such as the Quality of Life Index for Mental Health, are under development and there is increasing interest in evaluating more broadly the impact of treatment of patient indices of functioning and well-being in schizophrenia. Research, over the last few years, has focused on understanding the impact of major depression and anxiety and treatment for these disorders on HRQL. Existing generic health status measures, such as those developed for the Medical Outcomes Study, are increasingly incorporated into clinical trials of new antidepressant treatments. Unfortunately, most of these have not reached publication. Several depressionspecific measures, such as the SmithKline Beecham Quality of Life scale. Quality of Life Enjoyment and Satisfaction Questionnaire, and the Quality of Life in Depression scale, have been developed and are beginning to be used in clinical studies. However, there is only limited information available about the reliability, validity and responsiveness of most of these new scales.The selection of HRQL measures and the design of HRQL components for clinical trials needs to be guided by the objectives of the research, the target population, and the potential positive and negative consequences of the pharmacological treatment. Selection of specific instruments is based on the relevance of the measure, the reliability and validity of the scale, and practical considerations. The ability of a HRQL scale to discriminate between persons with different severity of disease, and the responsiveness to change are critical treatment evaluations. Practical characteristics include respondent and investigator burden, and the mode of administration of the scale. In the design of a clinical trial, attention must be focused on identifying appropriate data collection intervals to detect important changes in HRQL, if they should occur, and in addressing logistical and practical issues associated with the administration of HRQL scales.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS