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Biomedical subjects

L F Gram

Publications and source records attributed to L F Gram.

At least 19 recordsLinked to original sources

Socio-economic inequalities in first-time use of antidepressants: a population-based study.

OBJECTIVE: To analyse whether first-time use of antidepressants (incidence) and selection of TCAs (tricyclic antidepressants) versus new-generation drugs are associated with socio-economic status and psychiatric history. METHOD: We conducted a population-based cohort study using registry data covering Funen County, Denmark. A total of 305,953 adult residents without antidepressant prescriptions 5 years prior to the study period (1998) were included. RESULTS: The 1-year incidence rate of antidepressant prescription (1.7%) increased with age. It was higher in people who were female, less educated, unemployed, those receiving old-age or disability pension, low-income groups, and singles. The proportion prescribed new-generation antidepressants (82%) showed no difference according to socio-economic variables (education, annual income and socio-economic group), but was higher among the young and single. Admission to psychiatric hospital within 4 years prior to the study period was associated with high-incidence rate of antidepressant prescription and overall a preference for the new-generation antidepressants. CONCLUSION: Socio-economic status did not seem to influence the selection of TCAs versus new-generation antidepressants. Compatible with the general epidemiology of depression, low socio-economic status was associated with a high number of first-time users of antidepressants in the population, and the incidence rate increased with age.

Adolescent↗

Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial.

BACKGROUND: Tricyclic antidepressants (TCA) are often used in the treatment of painful polyneuropathy. Venlafaxine is a serotonin and weak noradrenaline reuptake inhibitor antidepressant with a different profile of other pharmacologic actions from those of TCA. OBJECTIVE: To test if venlafaxine would relieve painful polyneuropathy and compare its possible efficacy with that of the TCA imipramine. METHODS: The study design was randomized, double blind, and placebo controlled, with a three-way crossover. Forty patients were assigned to one of the treatment sequences, and 29 completed all three study periods. The daily doses were venlafaxine 225 mg and imipramine 150 mg. During the three treatment periods, each of 4 weeks' duration, patients rated pain paroxysms, constant pain, and touch- and pressure-evoked pain by use of 0- to 10-point numeric rating scales. RESULTS: The sum of the individual pain scores during treatment week 4 was lower on venlafaxine (80% of baseline score; p = 0.006) and imipramine (77%; p = 0.001) than on placebo (100%) and did not show any statistical difference between venlafaxine and imipramine (p = 0.44). The individual pain scores for pain paroxysms, constant pain, and pressure-evoked pain showed a similar pattern, whereas touch-evoked pain was uncommon and was not altered by any of the drugs. Numbers needed to treat to obtain one patient with moderate or better pain relief were 5.2 for venlafaxine and 2.7 for imipramine. CONCLUSION: Venlafaxine relieves pain in polyneuropathy and may be as effective as imipramine.

Adult↗

Are there differences in the use of selective serotonin reuptake inhibitors and tricyclic antidepressants? A prescription database study.

AIM: The aim of the present study was to analyse the utilisation of antidepressants (ADs) and to compare the utilisation of the various ADs with special reference to duration of treatment courses. METHOD: From the Odense Pharmacoepidemiologic Database (OPED), all users of and prescriptions for ADs in the County of Funen, Denmark (about 470,000 inhabitants), were identified for each year from 1992 to 1997 (6 years). Duration of treatment courses was calculated for the first incident period of continuous use of one AD and was compared for the various ADs using Kaplan-Meiers survival statistics with log rank tests. Continuous use was defined as use of a minimum of one tablet per day. Furthermore, the proportion of users presenting only one prescription was determined for each AD. RESULTS: In total, 37,598 patients presented 392,524 prescriptions during 1992-1997. The 1-year prevalence rose from 2.1% to 4.1% in 1997 and the incidence was 1.3% in 1997. The 1-year prevalence increased with age up to 16.5% in 1997 for patients aged 90 years or older. Citalopram was the most-used AD, but there were still a considerable number of patients commencing treatment with TCAs in 1997. Median duration of treatment courses was 196 days for TCAs versus 120 days for SSRIs (P < 0.0001). Duration of treatment courses increased with age. The proportion of users presenting only one prescription was 22% for the SSRIs versus 33% for tricyclic antidepressants (TCAs). CONCLUSION: This study showed that the use of ADs continues to increase because of the increase in the use of the new ADs. There was, however, still a considerable number of patients who started on TCA treatment in 1997. For repeated prescriptions, TCAs were used for longer times than SSRIs. In the very old, there was an apparently inappropriate high use of ADs.

Adult↗

Changes in the utilisation of lipid-lowering drugs over a 6-year period (1993-1998) in a Danish population.

OBJECTIVE: The effect of lipid-lowering drugs (LLDs) on coronary heart disease is well established. However, their utilisation is often suspected to be too low. The aim of this study was to describe the epidemiology of LLD use with special emphasis on the development of utilisation over a 6-year period in a Danish population. METHODS: For all people who purchased LLDs from 1993 to 1998 in Funen County, all prescriptions for LLDs and co-medication with cardiovascular and antidiabetic drugs were retrieved from Odense University Pharmacoepidemiologic Database (OPED). RESULTS: During the study period, LLD use increased nearly exponentially. In 1998, statins accounted for 95% of the total LLD consumption. The incidence increased markedly around the time of the publication of the Scandinavian Simvastatin Survival Study (4S). Only 3% of the statins were purchased without reimbursement. The female/male ratio was 0.69 and the median age was 60 years. General practitioners issued 73% of the total number of LLD prescriptions, and 55% of the treatments were initiated in general practice. A larger fraction of females and elderly started treatment in general practice. About 40% of the treatments were hospital initiated, and about one-third were followed up in general practice within the first year. CONCLUSIONS: Over the 6 years studied, utilisation of LLDs approached a level that may correspond to the current guideline recommendations. Compliance with guidelines should, however, be studied by following people with coronary heart disease.

Aged↗

The analgesic effect of codeine as compared to imipramine in different human experimental pain models.

The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection/tolerance thresholds to single electrical sural nerve stimulation and pain summation at tolerance threshold to repetitive electrical sural nerve stimulation (temporal summation) and pain experienced during the cold pressor test, rated as peak pain intensity, pain average intensity and discomfort. Compared to placebo, imipramine significantly increased pressure pain tolerance threshold (P = 0.03) and increased pain tolerance threshold (P = 0.05) and pain summation threshold (P = 0.03), but not pain detection threshold to electrical stimulation. Imipramine did not cause significant changes in pain perception during the cold pressor test. Codeine significantly increased pressure pain tolerance threshold (P = 0.02), pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain summation threshold (P = 0.02) to electrical stimulation. In addition, codeine reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is concluded that both imipramine and codeine inhibit temporal pain summation, whereas only codeine reduces cold pressor pain. Pain summation may be a key mechanism in neuropathic pain. Imipramine has a documented effect on such pain conditions on temporal summation. The present study showed that codeine also inhibits temporal summation, which is in line with the clinical observations indicating that opioids relieve neuropathic pain.

Adrenergic Uptake Inhibitors↗

Psychopharmacological treatment and psychiatric morbidity in 390 cases of suicide with special focus on affective disorders.

OBJECTIVE: The aim of this study was, on the basis of data from health-care registers, to describe the adequacy of psychopharmacological treatment in suicides. METHOD: Data on consecutive suicides in a Danish County (Funen) in the period of 1 April 1991-31 December 1995 were identified in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense University Pharmacoepidemiological Database. RESULTS: Twenty-five per cent of the suicides previously hospitalized due to affective disorders and 3% of the suicides without psychiatric hospitalizations at all, received an apparently adequate treatment with antidepressants the month before suicide. CONCLUSION: The most striking finding was the insufficiency of treatment with antidepressants in the group of suicides without psychiatric hospitalization, in particular in light of the fact that depression is assumed to be present in at least 50% of all suicides.

Adult↗

CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages.

OBJECTIVE: This review aimed to provide distinct dose recommendations for antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and CYP2C19. This approach may be a useful complementation to clinical monitoring and therapeutic drug monitoring. METHOD: Our literature search covered 32 antidepressants marketed in Europe, Canada, and the United States. We evaluated studies which had compared pharmacokinetic parameters of antidepressants among poor, intermediate, extensive and ultrarapid metabolizers. RESULTS: For 14 antidepressants, distinct dose recommendations for extensive, intermediate and poor metabolizers of either CYP2D6 or CYP2C19 were given. For the tricyclic antidepressants, dose reductions around 50% were generally recommended for poor metabolizers of substrates of CYP2D6 or CYP2C19, whereas differences were smaller for the selective serotonin reuptake inhibitors. CONCLUSION: We have provided preliminary average dose suggestions based on the phenotype or genotype. This is a first attempt to apply the new pharmacogenetics to suggest dose-regimens that take the differences in drug metabolic capacity into account.

Antidepressive Agents↗

Specific effect of venlafaxine on single and repetitive experimental painful stimuli in humans.

BACKGROUND: Tricyclic antidepressants relieve neuropathic pain, and the analgesic properties of tricyclic antidepressants are substantiated in human experimental pain models. It has been speculated that drugs with a selective inhibition of presynaptic reuptake of both serotonin and noradrenaline could have an analgesic effect comparable to the analgesic effect of tricyclic antidepressants. OBJECTIVE: Our objective was to evaluate the analgesic effect of the serotonin-noradrenaline reuptake inhibitor venlafaxine in human experimental pain models. METHOD: The study was carried out as a randomized, placebo-controlled, double-blind, crossover experiment that included 16 healthy volunteers. A 37.5-mg dose of venlafaxine was given orally 4 times with 12-hour intervals, and pain tests were performed before and 3 hours after the second and fourth doses. Pain tests included the determination of pain detection and tolerance thresholds to pressure, pain detection and tolerance thresholds on single electrical transcutaneous stimulation of the sural nerve, pain temporal summation on repetitive electrical sural nerve stimulation, and pain experienced during the cold pressor test. RESULTS: Venlafaxine increased thresholds for pain tolerance after single electrical stimulation (P =.005) and pain summation (P =.01) on repetitive stimulation but did not alter the thresholds for pain detection after single electrical sural nerve stimulation. Venlafaxine did not alter pain experienced during the cold pressor test or increase the pressure pain thresholds. CONCLUSION: Venlafaxine increases the pain tolerance threshold to electrical sural nerve stimulation and the threshold at which pain increases (pain summation). The impact of venlafaxine on pain summation in this experimental pain model on repetitive stimulation may indicate a potential analgesic effect for clinical neuropathic pain.

Adult↗

Contacts to the health care system prior to suicide: a comprehensive analysis using registers for general and psychiatric hospital admissions, contacts to general practitioners and practising specialists and drug prescriptions.

OBJECTIVE: The purpose of this study was to describe suicides' contacts with various parts of the health-care system. METHOD: Data on 472 people who committed suicide in a Danish County (Funen) in the period of April 1 1991 to December 31 1995 were searched in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense Pharmacoepidemiologic Database. RESULTS: In total, 97.5% of the suicides were recaptured in at least one of these registers. Forty-two per cent had been hospitalized in psychiatric departments. Within the last month before death, 66% consulted a general practitioner, 13% and 7%, respectively, were discharged from a psychiatric hospital and general hospital. CONCLUSION: The registers used provided a comprehensive registry-based description of suicides' contacts with the health-care system. The most prominent features were the high prevalence of psychiatric morbidity and the high rate of contacts with GPs close to suicide.

Age Factors↗

Are in-patient depressives more often of the melancholic subtype? Danish University Antidepressant Group.

In contrast to out-patients, hospitalized depressed patients have been reported to respond better to tricyclic antidepressants (TCAs) than to selective serotonin reuptake inhibitors (SSRIs) and moclobemide. This may be due to differences in the type of patients included in the trials. The hypothesis that hospitalized depressed patients have a different symptom profile to out-patients was tested by comparing 352 patients from three in-patient studies with 581 patients from three out-patient studies conducted in Denmark during the period 1980-1992. All patients had major depression and were evaluated using the Hamilton Depression Scale. The full version of the Newcastle Diagnostic Rating Scale (1965) was applied to 443 of the patients. In-patients were characterized by higher scores on the items 'depressed mood', 'suicidal impulses', 'work and interest (reduced)', 'retardation', 'distinct quality of depression', 'weight loss', 'feeling of guilt' and 'nihilistic delusions', and by lower scores on the items 'somatic complaints', 'hypochondriasis', 'psychological stressors' and 'anxiety'. In total, 76% of the in-patients and 40% of the out-patients had melancholic/endogenous depression. These findings may explain why TCAs are superior to SSRIs and moclobemide in hospitalized patients, since other data indicate that TCAs seem to be the most effective treatment for the melancholic/endogenous subtype.

Ambulatory Care↗