Lolkje T. W. de Jong-van den Berg

Valproic acid monotherapy in pregnancy and major congenital malformations

BACKGROUND The use of valproic acid in the first trimester of pregnancy is associated with an increased risk of spina bifida, but data on the risks of other congenital malformations are limited. METHODS We first combined data from eight published cohort studies (1565 pregnancies in which the women were exposed to valproic acid, among which 118 major malformations were observed) and identified 14 malformations that were significantly more common among the offspring of women who had received valproic acid during the first trimester. We then assessed the associations between use of valproic acid during the first trimester and these 14 malformations by performing a case-control study with the use of the European Surveillance of Congenital Anomalies (EUROCAT) antiepileptic-study database, which is derived from population-based congenital-anomaly registries. Registrations (i.e., pregnancy outcomes with malformations included in EUROCAT) with any of these 14 malformations were compared with two control groups, one consisting of infants with malformations not previously linked to valproic acid use (control group 1), and one consisting of infants with chromosomal abnormalities (control group 2). The data set included 98,075 live births, stillbirths, or terminations with malformations among 3.8 million births in 14 European countries from 1995 through 2005. RESULTS Exposure to valproic acid monotherapy was recorded for a total of 180 registrations, with 122 registrations in the case group, 45 in control group 1, and 13 in control group 2. As compared with no use of an antiepileptic drug during the first trimester (control group 1), use of valproic acid monotherapy was associated with significantly increased risks for 6 of the 14 malformations under consideration; the adjusted odds ratios were as follows: spina bifida, 12.7 (95% confidence interval [CI], 7.7 to 20.7); atrial septal defect, 2.5 (95% CI, 1.4 to 4.4); cleft palate, 5.2 (95% CI, 2.8 to 9.9); hypospadias, 4.8 (95% CI, 2.9 to 8.1); polydactyly, 2.2 (95% CI, 1.0 to 4.5); and craniosynostosis, 6.8 (95% CI, 1.8 to 18.8). Results for exposure to valproic acid were similar to results for exposure to other antiepileptic drugs. CONCLUSIONS The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.

A three-country comparison of psychotropic medication prevalence in youth

BackgroundThe study aims to compare cross-national prevalence of psychotropic medication use in youth.MethodsA population-based analysis of psychotropic medication use based on administrative claims data for the year 2000 was undertaken for insured enrollees from 3 countries in relation to age group (0–4, 5–9, 10–14, and 15–19), gender, drug subclass pattern and concomitant use. The data include insured youth aged 0–19 in the year 2000 from the Netherlands (n = 110,944), Germany (n = 356,520) and the United States (n = 127,157).ResultsThe annual prevalence of any psychotropic medication in youth was significantly greater in the US (6.7%) than in the Netherlands (2.9%) and in Germany (2.0%). Antidepressant and stimulant prevalence were 3 or more times greater in the US than in the Netherlands and Germany, while antipsychotic prevalence was 1.5–2.2 times greater. The atypical antipsychotic subclass represented only 5% of antipsychotic use in Germany, but 48% in the Netherlands and 66% in the US. The less commonly used drugs e.g. alpha agonists, lithium and antiparkinsonian agents generally followed the ranking of US>Dutch>German youth with very rare (less than 0.05%) use in Dutch and German youth. Though rarely used, anxiolytics were twice as common in Dutch as in US and German youth. Prescription hypnotics were half as common as anxiolytics in Dutch and US youth and were very uncommon in German youth. Concomitant drug use applied to 19.2% of US youth which was more than double the Dutch use and three times that of German youth.ConclusionProminent differences in psychotropic medication treatment patterns exist between youth in the US and Western Europe and within Western Europe. Differences in policies regarding direct to consumer drug advertising, government regulatory restrictions, reimbursement policies, diagnostic classification systems, and cultural beliefs regarding the role of medication for emotional and behavioral treatment are likely to account for these differences.

Chlorpromazine equivalents versus defined daily doses: How to compare antipsychotic drug doses?

Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD). The DDD is the assumed average maintenance dose per day for a drug if used for its main indication in adults. The DDD is based on review of the available older and recent literature. In this report, we evaluated discrepancy between CPZ-equivalent values and DDD-equivalent values. We plotted CPZ-equivalent values against DDD-equivalent values and performed linear regression to determine the mean relationship between the 2 methods. About 67% of the DDD-equivalent values demonstrated lower potencies for antipsychotic drug compared with CPZ-equivalent values. The slope of the regression line was 0.68 (r2 = 0.81). Because we found a great discrepancy between these 2 methods of comparing antipsychotic drug doses, we think further research is necessary to develop a standardized way of antipsychotic drug comparison.

Consumer Adverse Drug Reaction Reporting A New Step in Pharmacovigilance

The direct reporting of adverse drug reactions by patients is becoming an increasingly important topic for discussion in the world of pharmacovigilance. At this time, few countries accept consumer reports.We present an overview of experiences with consumer reporting in various countries of the world. The potential contribution of patient reports of adverse drug reactions is discussed, both in terms of their qualitative and quantitative contribution. The crucial question is one of whether patient reports will increase the number and quality of the reports submitted and/or lead to a more timely detection of signals of possible adverse reactions, thus contributing to an enhancement of the existing methods of drug safety monitoring. To date, the data available are insufficient to establish such added value.

Unlicensed and off label drug use by children in the community: cross sectional study

Editorial by Banner and pp 1311, 1313 Studies in various hospital settings showed that many drugs taken by children either are not licensed or are used outside the terms of the product licence.1–3 Information on the extent of paediatric labelling of drugs taken by children in the community is, however, limited and based on small study populations. 4 5 We studied drugs taken by children in the community, based on the pharmacy records of prescriptions from both general practitioners and outpatient departments. We aimed to determine the number of prescriptions for unlicensed drugs for children in the community and to investigate paediatric labelling of all drugs with a product licence to determine the extent of off label use. In the Netherlands …

Use of Antipsychotic Drugs Among Dutch Youths Between 1997 and 2005

OBJECTIVE The authors examined prevalence, incidence, and duration of antipsychotic drug use in the northern and eastern regions of the Netherlands between 1997 and 2005 among youths in regard to age, gender, and class of drug. METHODS Prescription drug dispensing data were collected from community pharmacies in the northern Netherlands (www.iadb.nl). Prevalence, incidence, and duration of use were studied among roughly 100,000 youths ranging in age from infancy to age 19 years, calculated by age group (zero to four years, five to nine years, ten to 14 years, and 15 to 19 years), for boys and girls, and for first- and second-generation antipsychotics. Duration of use was compared between youths who started antipsychotic treatment in 1998-1999 and those who started in 2001-2002. RESULTS From 1997 to 2005, prevalence increased from 3.0 to 6.8 per thousand. Prevalence was highest among ten-year-olds to 14-year-olds (11 per thousand), especially among boys (17 per thousand). The increased prevalence was mainly attributable to an increased use of second-generation antipsychotics and to a longer duration of use. Median duration of use doubled from .8 year in 1998-1999 to 1.6 years in 2001-2002. CONCLUSIONS Second-generation antipsychotic drugs were increasingly prescribed, and for longer periods of time, to younger children, probably because of new indications. This practice increases the exposure of a young population to (partly unknown) risks.

The history of DES, lessons to be learned

Since the 1940s, diaethylstilbestrol (DES) has been used by millions of pregnant women to prevent miscarriages and many other disorders in pregnancy. In 1971, it became clear that this apparently innocent treatment proved to be a time bomb for the infants exposed to DES during the first trimester of pregnancy. DES is now associated with an increased risk of breast cancer, clear cell adenocarcinoma (CCAC) of the vagina and cervix, and reproductive anomalies. This article summarises the potential long-term health implications of DES on the mother, DES daughters and DES sons, and the possible side effects on the third generation. Health care professionals have to know the history of DES to prevent future disasters with drugs prescribed.

The population-based prescription database IADB.nl: its development, usefulness in outcomes research and challenges

Research databases with large numbers of prescriptions in observational settings can provide valuable information in addition to the initial randomized controlled trials. This paper reports on the development of prescription database IADB, formerly known as InterAction Database. IADB contains prescriptions from 54 community pharmacies in The Netherlands and covers a population of 500,000 people. Both the age distribution and the prevalence of drugs used are comparable to a large extent with the Dutch population. The representativeness of the population covered is examined by comparing population composition and drug use with data of the whole Dutch population. Enriching IADB with, among others, clinical parameters by linking to other databases is explored. A strong and unique aspect of IADB is the possibility to track patients over time, even when they receive their medication from different pharmacies. The authors conclude IADB is a useful tool for pharmacoepidemiological and pharmacoeconomic outcomes research.

The InterAction Database: Synergy of Science and Practive in Pharmacy

In social pharmacy and pharmacoepidemiology the distribution, use and performance of medication after registration is studied. In both fields, the pharmacists are the main source of data on drug use. To increase the value of research, we think it important to exchange ideas and suggestions between scientific researchers and pharmacists who work in community pharmacies. Hence, the department of Social Pharmacy and Pharmacoepidemiology of the University of Groningen sought close collaboration with some community pharmacies in the region, resulting in the InterAction project. The pharmacists deliver data to the InterAction database and are explicitly invited to raise questions and issues from their practice, and to participate in research. Consequently, science and practice benefit from each others input and expertise. This paper describes the architecture and contents of the InterAction project. Additionally, the first experiences with the database as a laboratory for social pharmacy and pharmacoepidemiology are discussed.

Ten years after the Dutch public health campaign on folic acid: the continuing challenge

Background Folic acid use in the periconceptional period reduces the risk of neural tube defects (NTDs). However, applying this knowledge in daily practice is not an easy task. We report here the current level of folic acid use in the Netherlands and discuss the figures within the framework of a national governmental campaign held in 1995 promoting the use of folic acid and the professional interventions undertaken since then. Methods We carried out six studies in the northern Netherlands during 1995, 1996, 1998, 2000, 2003 and 2005, respectively. The same methodology in the same health professionals’ practices was followed in all studies. Pregnant women attending their first or second antenatal visit were asked to fill in a questionnaire aimed at assessing their awareness and use of folic acid. Results In 2005, most of the pregnant women used folic acid “at some time in their pregnancy”, and 51% used it for the entire advised period. Prior knowledge on the protective affect of folic acid and on the period of use was strongly related to the level of education. The use of folic acid in a previous pregnancy [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.6–9.9], the use of an oral contraceptive (OR 2.1, 95% CI 1.1–4.1) and parity (OR 0.08, 95% CI 0.01–0.5) significantly predicted the current correct use. The most recent figures revealed that there is still a large gap between more highly and less educated women in terms of taking folic acid in the advised period: 63 versus 31%, respectively. Discussion The aim of the Dutch Ministry of Health is to have 70% of Dutch women wanting to become pregnant use folic acid supplements in the advised period by 2010. While this level has almost been reached among more highly educated women (63%), it will take a great deal more effort, money and creativity to achieve the necessary increase from the current level of 31% among women with a lower educational background.BackgroundFolic acid use in the periconceptional period reduces the risk of neural tube defects (NTDs). However, applying this knowledge in daily practice is not an easy task. We report here the current level of folic acid use in the Netherlands and discuss the figures within the framework of a national governmental campaign held in 1995 promoting the use of folic acid and the professional interventions undertaken since then.MethodsWe carried out six studies in the northern Netherlands during 1995, 1996, 1998, 2000, 2003 and 2005, respectively. The same methodology in the same health professionals’ practices was followed in all studies. Pregnant women attending their first or second antenatal visit were asked to fill in a questionnaire aimed at assessing their awareness and use of folic acid.ResultsIn 2005, most of the pregnant women used folic acid “at some time in their pregnancy”, and 51% used it for the entire advised period. Prior knowledge on the protective affect of folic acid and on the period of use was strongly related to the level of education. The use of folic acid in a previous pregnancy [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.6–9.9], the use of an oral contraceptive (OR 2.1, 95% CI 1.1–4.1) and parity (OR 0.08, 95% CI 0.01–0.5) significantly predicted the current correct use. The most recent figures revealed that there is still a large gap between more highly and less educated women in terms of taking folic acid in the advised period: 63 versus 31%, respectively.DiscussionThe aim of the Dutch Ministry of Health is to have 70% of Dutch women wanting to become pregnant use folic acid supplements in the advised period by 2010. While this level has almost been reached among more highly educated women (63%), it will take a great deal more effort, money and creativity to achieve the necessary increase from the current level of 31% among women with a lower educational background.