Diagnosis and management of depression in general practice.
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Biomedical subjects
Publications and source records attributed to G Beaumont.
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The rationale for the development of Repertory-Grid based quality of life assessment (QOL) is described. The emergent scale, the SmithKline Beecham Quality of Life Scale (SBQOL) utilizes 23 predetermined constructs and three fixed elements: self now, ideal self and sick self. Inclusion of the latter two elements provides a personal frame of reference for the individual and recognizes the highly idiosyncratic and subjective nature of the experience which constitutes quality of life. A study of the validity and reliability of the SBQOL was conducted in 129 patients presenting to their GP with either major depression or generalized anxiety disorder, as defined by DSM III R. Patients were treated at the discretion of their GP and followed over a period of 12 weeks with assessments of treatment efficacy being performed at 6 weeks and 12 weeks in parallel with administration of the SBQOL. The results from co-administration of standard efficacy measures such as the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) with the SBQOL, provided good evidence of construct validity. Evidence in support of the concurrent validity of the SBQOL was provided by co-administration of the Sickness Impact Profile and General Health Questionnaire (external criteria) with the SBQOL scale. Test-retest reliability and internal consistency were high. No obvious advantage was conferred by the use of principal components analysis from the Flexigrid software package in contrast to a simple arithmetical procedure for computing interelement distances. It is concluded that the SBQOL provides a valid, reliable and practicable approach to the assessment of quality of life in patients with affective disorder.
Suicide is a complex and confusing subject. Although social factors may be important a clear relationship has been established between suicide and some medical conditions, notably depression, schizophrenia and alcohol dependence. Primary care physicians are in the "front line" as far as the recognition of suicidal risk is concerned. There is good evidence that many individuals who commit suicide have had recent contact with medical services. Those who have attempted suicide are at a much greater risk of subsequently completing the act than the general population. Poisoning by solids or liquids is a common method of committing suicide. Prescribed medication is often used. Antidepressants vary considerably in their toxicity in overdosage. Newer compounds, including moclobemide appear to be safer than older ones. There is some evidence that suicide rates can be influenced by changing the availability of lethal substances and methods. It is suggested the prescription of toxic antidepressants should be restricted or avoided in patients in whom the risk of suicide is high.
A single-blind, multicentre, comparative clinical trial was performed in 59 hayfever sufferers to compare the efficacy of mequitazine 5 mg bd and terfenadine 60 mg bd over a period of 14 days. Clinical assessments of nasal and ocular symptoms were made on admission to the trial and after seven and 14 days treatment by both physicians and patients. Critical flicker fusion threshold was measured at each assessment. A global assessment of efficacy was determined by both the doctor and patient at the end of treatment. Patients also completed a daily diary card. Thirty patients on mequitazine and 22 on terfenadine completed the trial. There were seven dropouts (five on terfenadine and two on mequitazine). Both treatments were equally effective in reducing the severity of symptoms over the 14 days of treatment. The overall assessment at the end of treatment showed no important significant differences between the two drugs. According to the physicians, 60 per cent of the mequitazine-treated patients and 63 per cent of the terfenadine-treated patients had an excellent or good response. Patients assessed their response as excellent or good in 56 and 62 per cent of cases respectively. Neither drug significantly impaired performance.
This was an open study of the efficacy and acceptability of zopiclone 7.5 mg nocte as a somnifacient. The study population comprised 108 insomniac patients (70 female, 38 male) aged 22-74 years who received zopiclone 7.5 mg for 7 consecutive nights. Based on subjective sleep assessments, zopiclone reduced the patients' difficulty in falling asleep, increased the number of hours slept and decreased the number of nocturnal awakenings (p less than 0.001). The majority of patients reported sleeping well or very well. The quality of sleep improved (p less than 0.0001), and the incidence of waking earlier than desired decreased (p less than 0.001), with respect to baseline, after receiving zopiclone. Physicians rated efficacy as good or very good in the majority of patients. Zopiclone was efficacious both in patients who had not previously received hypnotic therapy (n = 37) and in patients who transferred directly to zopiclone from a benzodiazepine hypnotic (n = 26). Whilst receiving zopiclone, patients reported feeling better in the morning than they did prior to treatment (p less than 0.004); 78% expressing satisfaction with zopiclone as an hypnotic. Physicians reported zopiclone treatment to be without side-effects in the majority of patients. In conclusion, zopiclone appears to be an effective and well-tolerated hypnotic that may play a role in the treatment of insomnia in the general population.
This paper attempts to summarize a personal approach to the management of anxiety and to some of the problems that have been recently encountered in respect of public attitudes to benzodiazepines. In the management of anxiety 'psychological' approaches should be sought where possible. There are, however, occasions, both in connection with normal and abnormal anxiety, when drug therapy is appropriate or where perhaps a combination of 'psychological' and pharmacological methods represents the most expedient course of action. Prescribers need an 'armamentarium' of drugs, since no one type of anxiolytic meets all our needs. The paper suggests limited use of benzodiazepine, beta blockers, low dose neuroleptics, some newer anxiolytic agents and certain specific drugs. The general practitioner needs to tailor his choice to the needs and attributes of particular patients.
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The subject of dosage of clomipramine (Anafranil) in depression and in obsessional and phobic disorders is discussed. The expectation of success is reported and a recommendation made to adopt flexible dosage. Some side-effects are considered and stress is laid on distinguishing between unwanted pharmacological effects and serious toxic effects. Serious adverse reactions are rare. Contra-indications, both relative and absolute, are discussed. The importance of possible drug interactions is emphasized.
Some of the problems inherent in the measurement of mood are considered. Various physician rating and patient self-rating instruments are described which may have practical application in general practitioner trials. The need for continuing research in the area of the measurement of mood disturbance in the setting of general practice is stressed.
Two trials of maprotiline (Ludiomil) were performed in general practice. In the first study depressed patients were given either 75 mg of maprotiline in a single dose or 25 mg three times daily. Assessments of the severity of depression and of side-effects were made initially and following 1, 2 and 4 weeks' treatment. At each assessment measurements of plasma levels of maprotiline were made. A second trial was performed in which some patients receiving 75 mg single dose of maprotiline had whole blood levels of maprotiline assayed. Steady-state levels of maprotiline were achieved after one week but these levels showed considerable individual variability. No clear correlation emerged between clinical response, side-effects and plasma or blood levels. Some of the factors which may be responsible are discussed.
In a large, open, multicentre trial, conducted in general practice, 765 patients suffering from agoraphobia or social phobias were treated with clomipramine (Anafranil, Geigy Pharmaceuticals). Four hundred and eight patients completed a twelve-week course of treatment. Of 285 withdrawals, 139 were due to side-effects. Good results were obtained on all measures of phobias in those patients who completed the study, the improvements being of the order of 70-80%, and over 50% of patients being symptom-free.
Two assessment schemes for assessing obsessional and phobic disorders are described. The schemes were constructed with the phenomenology and epidemiology of the disorders in mind and were designed for use in the setting of general practice.
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Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.
Patients treated with four dosage regimes of clomipramine (Anafranil) 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. in a clinical trial lasting four weeks were regularly weighed. Due allowance was made for the normality or otherwise of normal weight, appetite and, in women, menstruation. There was no evidence that during the four weeks of this particular study and on these doses of clomipramine patients showed any increase in weight.
An attempt was made to measure the effects of depressive illness and of clomipramine (Anafranil) therapy in doses of 30 mg and 75 mg daily on sexual appetite and performance. A special questionnaire was devised to gather information on sexual habits before illness, during illness and following treatment. It proved difficult to differentiate between the beneficial effects of recovery from depression and the possible adverse drug effects on sexual activity. Two patients dropped out of the study because of supposed sexual side-effects--a male with ejaculatory difficulties and a female with orgasmic impotence. Fifty-four patients completed the sexual questionnaire and a four-week course of clomipramine. There were nineteen males and thirty-five females. Sixty-eight per cent of males and 57% of females had their 'sex life' impaired by depressive illness. Coital rate was decreased and depression interfered with performance and satisfaction. Clomipramine therapy seemed to have advantageous and disadvantageous effects. The advantageous effects were probably associated with improvement in depressive illness. There was evidence that clomipramine had an adverse effect sexually in 26% of males and 14% of females. The effect was dose-related in females.