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.

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.

Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study.

BACKGROUND: Biochemical liver function tests are widely used in the clinic and are some of the most frequently used tests in screening for diseases in older age groups. The aim of the present study was to estimate the relative importance of genetic and environmental factors to variations in these tests among the elderly. METHODS: We conducted a survey among Danish twins, 73-102 years of age, identified in the population-based Danish Twin Registry. Among the 2749 individuals in the study population, an interview was conducted with 79%. From these, a blood sample was collected from 290 same-sex twin pairs, total of 580 subjects, within a 6-month period and analyzed for alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and albumin. The interview included questions about alcohol consumption and body mass index (BMI; self-calculated height and weight). Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses before and after correction for alcohol consumption and BMI. RESULTS: Structural-equation analyses revealed a substantial heritability (35-61%) for the four biochemical liver function tests: ALT, GGT, LDH, and bilirubin. The remaining variation could be attributed to individuals' nonfamilial environments. Adjustment for alcohol consumption and BMI had no influence on the heritability for ALT, GGT, LDH, and bilirubin. For albumin, two models fit equally well before adjustment for alcohol and BMI: a model including additive genetic and nonshared environmental factors (AE), and a model including shared and nonshared environmental factors (CE). After adjustment, the model including shared and nonshared environment was clearly the best fitting model. CONCLUSIONS: For both males and females, the effect of genetic factors on the biochemical liver function tests ALT, GGT, LDH, and bilirubin is substantial and accounts for one-third to two-thirds of the variation among individuals 73-102 years of age. The heritability is equal for males and females and does not change notably after controlling for alcohol consumption and BMI. For albumin, no major impact of genetic factors was found independent of BMI and alcohol consumption. An understanding of the genetic mechanisms underlying biochemical liver function tests among the very old may be of value in the interpretation of these tests in this age group.

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.

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.

[Polypharmacy estimated by means of a population-based prescription database]. / Polyfarmaci belyst ved hjaelp af en populationsbaseret receptdatabase.

The aim was to investigate estimators of polypharmacy (PP) from a population based prescription database. Data were retrieved from Odense Pharmacoepidemiological Database and contained a 10% random sample (n = 26,977) of drug users in 1994. PP was defined as simultaneous treatment with different drugs, and the duration of treatment was calculated from the date of purchase and the number of defined daily doses prescribed. This estimator was compared with an estimator based on the number of drugs purchased during a three month period. On an average day 8.7% were exposed to minor PP (two to four drugs) and 1.2% to major PP (five or more drugs). Purchase of five or more drugs during a three month period predicted episodes of major PP with a positive predictive value of 80%. Epidemiological measures of multiple drug use can be estimated from a prescription database. Conceptually, an estimator based on the number of simultaneously used drugs is preferable, but the number of drugs purchased during a three month period may be a useful alternative estimator.

Polypharmacy and the risk of drug-drug interactions among Danish elderly. A prescription database study.

OBJECTIVE: To analyze the use of all subsidized prescription drugs with special attention to the elderly (> or = 70 years of age), including their use of drug combination generally accepted as carrying a risk of severe interactions. DESIGN: Descriptive prevalence study. SETTING: Odense Pharmacoepidemiological Database, Denmark. The fourth quarter of 1994. SUBJECTS: All inhabitants in the county of Funen, Denmark. MAIN OUTCOME MEASURES: Prevalence of drug use for persons < 70 and > or = 70 years of age including number of drugs used and of drug combinations. Occurrence of 45 drug combinations generally accepted as carrying a risk of severe interactions. RESULTS: Among persons less than 70 years, 67.9% used none, 16.5% used one drug and 15.6% used two or more prescription drugs. The corresponding prevalences for the elderly were 35.7%, 15.9% and 48.4%. The 26,337 elderly patients with at least two drugs used 21,293 different combinations. Of the elderly patients who had purchased > or = two drugs, 4.4% had combinations of drugs carrying a risk of severe interactions. CONCLUSIONS: Most elderly use drugs and usually several drugs concomitantly. The elderly form a heterogeneous group of drug users. Drug combinations carrying a risk of severe interactions are relatively frequent.

Relationship between drug use and self-reported health in elderly Danes.

OBJECTIVE: To evaluate the relationship between drug use and self-rated health in the elderly. MATERIALS: An interview survey among all individuals aged 75 years or over in the Danish Twin Register took place. The survey comprised of 2171 persons who responded to questions on self-rated health and drug use. RESULTS: The mean number of all drugs used increased from 1.3 in persons with "very good" health to 4.6 in persons with "very poor" self-rated health. For prescription drugs, the corresponding figures were 0.5 vs 1.8, respectively. Among persons using no drugs, 45.8% reported "very good" health, compared with only 6.4% of the persons using five or more drugs. Only 4% of persons using no drugs reported "poor" or "very poor" health. Further, the probability of having a poorer self-rated health increased with the number of drugs used, even though the tendencies were less clear for users of three or more drugs, particularly in the oldest persons. Users of opioids clearly had a poorer self-rated health compared with users of other drug groups. CONCLUSION: This study shows a relationship between self-rated health and drug use among elderly. Danish twins, who have previously been shown to have health characteristics similar to those of the general population. This suggests that drug use is a good proxy for self-rated health and, in particular that limited drug use is a proxy for good health. This observation may point towards additional research potentials for automated drug databases.

[Antidepressive treatment in general practice--an interview study]. / Antidepressivabehandling i almen praksis--et interviewstudie.

In order to elucidate potential problems concerning the use of antidepressants in general practice, 98 randomly selected antidepressant users from 12 general practices were interviewed. The primary indication for antidepressant treatment was depression (72 patients), partly regular depression (therapeutic/prophylactic treatment) (n = 39), partly depressive tendencies (n = 32) (one patient no information). Median treatment duration was three years; 25% had been in treatment for more than 10 years. The general practitioners judged the treatment problematic/unacceptable in 23 cases, largely because of uncertain indication or because other or no treatment was considered better for the patient. Side effects were modest. The patients often had a relatively high depression score and poor status according to the WONCA-scale. The use of low doses, long duration of treatment, and uncertainty about the relevance of the treatment are important features in the use of antidepressants by general practitioners. The use of antidepressants in general practice differs from the scientifically-based recommendations.

Changes in the pattern of antidepressant use upon the introduction of the new antidepressants: a prescription database study.

OBJECTIVE: To study whether the newer antidepressants have changed the patterns of antidepressant use, and whether the claimed better adverse effect profile of the lower antidepressants is reflected in their use as monitored by a prescription database. METHOD: By means of a prescription database (OPED), the use of antidepressants from 1991 to 1993 in Odense, Denmark, was analysed. RESULTS: The 1-year prevalence of antidepressant use increased significantly from 1.60% to 2.00%, which still is below the claimed 1-year prevalence of depression of at least 5%. The increase was mainly due to a rapidly increasing use of the newer antidepressants, accompanied by a moderate decline in the use of older antidepressants (mainly tricyclic antidepressants). The patterns of antidepressant use were very polymorphic, with about 5% being on continuous use for all 3 years and groups of each 20-30% being treated with: (1) several series or (2) one series or (3) only by one prescription. The share of patients presenting only one prescription (20%) was the same for older and newer antidepressants. Likewise, the rate of shifts from older to newer antidepressants or vice versa was the same (7% vs 6%). The duration of treatment did not differ much between older and newer antidepressants. Relative to the defined daily dose (DDD), the older antidepressants were given in much lower doses (median 0.63 DDD) than the newer antidepressants (median 1.05 DDD). CONCLUSION: It is concluded that many depressed patients are still not receiving antidepressant treatment and that the claimed better adverse effect profile of the newer antidepressants was not clearly reflected in their use.

Methods for estimating the occurrence of polypharmacy by means of a prescription database.

OBJECTIVE: Concurrent use of multiple drugs (polypharmacy, PP) may cause health risks such as adverse drug reactions, medication errors and poor compliance. The objective of this study, based on data from a prescription database, was to evaluate estimators of PP in the general population. METHODS: Data were retrieved from Odense Pharmaco-epidemiological Database (OPED) and consisted of all prescriptions in 1994 from a 10% random sample of drug users (n = 26,977) in the county of Funen, Denmark. For each prescription, the period of consumption was calculated by setting the duration of treatment to equal the amount of drug purchased, as measured in defined daily doses (DDD), thereby assuming a daily intake of one DDD. PP was defined as overlapping periods of consumption for different drugs. A Venn diagram was used to illustrate and compare this estimator of PP with two other indicators of multiple-drug use: the number of drugs purchased in 3 months and the mean number of drugs used in 1 year. A receiver operating curve (ROC) was used to evaluate the possibility of predicting episodes of PP from the number of drugs purchased in 3 months. RESULTS: The proposed estimator of PP was robust towards changes in DDD. On an average day in 1994, the prevalence of PP was 9.9% and the standard deviation (SD) between days was 0.3%. Two to four drugs (minor PP) were used by 8.7% of the population (SD, 0.2%) and five or more drugs (major PP) by 1.2% (SD, 0.1%). The number of individuals displaying PP for the first time in 1994 stabilised after approximately 6 months, resulting in an incidence of major PP of 0.2% and of minor PP of 1.2% per month. For individuals exposed to PP, the median number of days of exposure was 61 and 10.5% were exposed for more than 350 days of the year. Purchase of five or more drugs in the first 3 months of 1994 predicted episodes of major PP in the same year with a positive predictive value of 80%. CONCLUSION: Epidemiological measures of multiple drug use can be estimated from data in a prescription database. From a conceptual point of view, an estimator based on the number of simultaneously used drugs (calculated from the date of purchase and the number of DDD) is preferable, but the number of drugs purchased in a 3-month period may also be a useful estimator.

Antidepressant treatment in general practice--an interview study.

OBJECTIVE: To elucidate potential problems concerning the use of antidepressants (AD) in general practice. DESIGN: Cross-sectional, descriptive interview study. SETTING: General practices, Odense, Denmark. SUBJECTS: Random sample consisting of 98 AD users from 12 general practices. MAIN OUTCOME MEASURES: Indication for AD treatment, justification of the treatment, duration of AD treatment, daily dose of AD, side effects, Hamilton depression rating, WONCA score. RESULTS: The primary indication for AD treatment was depression (72 patients), partly regular depression (therapeutic/prophylactic treatment) (n = 39), partly depressive tendencies (n = 32) (1 unknown). Median treatment duration was 3 years; 25% had been in treatment for more than 10 years. The general practitioners judged the treatment problematic/unacceptable in 23 cases, largely because of uncertain indication or because other or no treatment was considered better for the patient. The daily doses of AD were generally low. Side effects were modest. The patients often had a relatively high depression score and poor status according to the WONCA-scale. CONCLUSIONS: The use of low doses, long duration of treatment, and uncertainty about the relevance of the treatment are important features of the use of AD by general practitioners. There seems to be a discrepancy between the use of AD in general practice and the scientifically-based recommendations.

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism.

Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l.h-1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l.h-1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.

Concurrent use of more than one major psychotropic drug (polypsychopharmacy) in out-patients--a prescription database study.

1. In order to assess the prevalence of concurrent use of more than one major psychotropic drug (polypsychopharmacy) in out-patients, a prescription database study was conducted in the Odense area for a period of 2 years. 2. During the index period 5.12% of the inhabitants purchased major psychotropic drugs. Of these, 14% had a period of polypsychopharmacy recorded. The age-specific prevalence of users increased with age, the prevalence for over 90 years of age was 18%. Sixty-seven per cent of the psychotropic drug users were women. 3. For neuroleptic and antidepressant users, about 20% were subject to polypsychopharmacy, for lithium 61%. The most prevalent combination was neuroleptics-neuroleptics. In none of the 10 most prevalent combinations were the mean daily doses significantly lower on polypsychopharmacy compared with single drug regimens, in two they were higher. 4. Polypsychopharmacy with psychotropic drugs was frequent in out-patients. In polypsychopharmacy daily doses were not lowered in order to limit side effects.

[A short discharge letter with a copy to the patient--satisfactory for patients and practitioners]. / Kortfattet udskrivningsbrev med patientkopi--patienters og praktiserende laegers tilfredshed.

This study evaluated the introduction of a new type of discharge letter (DL). The new DL is hand-written by the discharging doctor on a form, and a copy is both given to the patient and sent immediately to the general practitioner (GP). Questionnaires were sent both to the receiving patients and GPs. One hundred and thirty-four patients (55%) and 157 GPs (87%) replied to the questionnaires. Half of the responding patients stated that the DL had helped them to understand what had happened during their hospital stay, as well as future plans for treatment. A majority of the responding GPs found the hospital stay, the patient's status at discharge and the planned after treatment to be satisfactorily described in the new DLs. Almost all GPs (90%) were pleased with the promptness with which they received the new DL. Compared to the traditional DL, 40% of the responding GPs found the new DL to be better and 29% found it to be worse.

Neuroleptic drug utilization in out-patients--a prescription database study.

1 A prescription database study was conducted to describe the out-patient utilization of neuroleptics in the Odense area (207,000 inhabitants) during a period of 1 year. 2 Neuroleptic drug use is widespread, the period prevalence being 2.45% of the population. 3 The prevalence increases with increasing age. Fifteen percent of the population aged 90 years or more received neuroleptic drugs in spite of the many warnings against side effects in the elderly. 4 Estimated daily doses of neuroleptics were considerably lower than the Defined Daily Dose, probably as a reflection of many neuroleptics being prescribed to non-psychotic patients, in whom lower doses are used. 5 For perphenazine, a comparison of estimated daily doses from this study with doses from patients whose treatment had been adjusted by plasma concentration monitoring showed that generally much lower doses were used by patients included in this study.

Outpatient utilization of antidepressants: a prescription database analysis.

A prescription database analysis was conducted to describe the users of antidepressants outside hospitals in the Odense area (207,000 inhabitants) during one year. In total, 1.62% (N = 3360) of the population used antidepressants. Women and users aged over 70 years constituted a disproportionately large part. Seventy-five percent of the patients used tricyclic antidepressants. The estimated daily doses for the tricyclic antidepressants were generally low, the third quartile being less than 100 mg daily. The low doses may be due to antidepressants being used on other indications than depression or that a considerable number of the patients are not given a sufficient dose.

[Consumption of addictive drugs among pensioners. A study of the consumption of benzodiazepines and strong analgesics among pensioners who receive drugs free-of-charge]. / Pensionisters brug af afhaengighedsskabende medicin. En undersøgelse af forbruget af benzodiazepiner og staerke analgetika hos pensionister med medicinkort.

The consumption of benzodiazepines and potent analgesics by old age pensioners and early retirees in Odense who had the right to receive medicine free-of-charge was accounted for where the month of March 1990 was concerned. Approximately 26% received financial support for benzodiazepines, 13% for analgesics while further 6% received support for both benzodiazepines and analgesics. The majority of the users were over 60 years and there twice as many women as men. No significant differences were observed in the sex and age distributions between the groups of pensioners who received benzodiazepines and/or analgesics and the group which received only other medicine. Both the direct and the indirect expenses are discussed. Furthermore, it is concluded that, in some of the pensioners, over-consumption is involved and that it is again necessary to emphasize the indications for prescription of these preparations.