Keywordsdrug utilization, exposure rate, pregnancy, selective serotonin reuptake inhibitors ---------------------------------------------------------------------- WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes.• However, the extent of SSRI use in pregnancy is largely unknown. WHAT THIS STUDY ADDS• In the last decade the use of SSRIs in the year preceding delivery has increased twofold. • This increase runs parallel with the increase in use of SSRIs among women of fertile age.• Paroxetine is one of the most commonly used SSRIs.• Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations.• The safety of SSRIs which are less frequently used is not yet established.• Case-control birth defect-monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs. AIMSRecent case-control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995-2004 in the Netherlands. METHODSThe study was performed with data from a population-based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2-year periods : 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the c 2 test for trend. RESULTSIncluded were 14 902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. CONCLUSIONThere has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.

Objective To investigate the utilization of antiepileptic drugs (AEDs) in Dutch children and compare this with guidelines on the treatment of epilepsy in children.Method From the Dutch Interaction Database (IADB.nl) we selected children aged 0-19 years who received at least one prescription for an AED (ATC-code beginning with N03A) between 1997 and 2005. We calculated cumulative incidences and prevalences per 1000 children per year, stratified by age-category, sex and type of AED, and the total number of months each patient received at least one prescription of AEDs, and we counted the number of person-months and AEDs prescribed. For each AED, proportions of person-months were calculated for monoand combination therapy. Kaplan-Meier survival analysis was used to analyse the duration of AED use, stratified by sex. Results The overall prevalence of the prescription of AEDs to children was constant at approximately 4.0 per 1000 children during the years of the study. The overall cumulative incidence from 1997-2005 was 0.67 per 1000 children. When stratified by age category or sex, there were no relevant differences in incidence or prevalence. Valproic acid was the most frequently prescribed drug, followed by carbamazepine and lamotrigine. In 20.3% of all personmonths, patients received combination therapy; of these, 34.2% received combination therapy for 3 person-months or less. The older AEDs were prescribed more often as monotherapy than combination therapy, in contrast with the newer AEDs, for which the opposite was true. The 50% survival probability (= time period when 50% of children had stopped using AEDs) was around 2 years, with a significantly lower discontinuation of treatment for girls than boys (P = 0.04). Conclusion The overall cumulative incidence of AEDs was determined to be 0.67 per 1000 children, and the prevalence 4.0 per 1000 children. The most frequently prescribed drug is valproic acid, followed by carbamazepine and lamotrigine. The prescribing of AEDs seems to be in conformity with the overall recommendations of the guidelines on the treatment of epilepsy in children.

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The co-medication patterns investigated yielded clinical as well as statistically significant different estimates. The estimates differed up to a factor 2.5 for the drugs usually prescribed for long periods, and a factor 12 for drugs prescribed for short periods. Hence, we propose to distinguish the patterns 'co-prescribing', 'concomitant medication,' and 'possibly concurrent medication.' The research question determines the co-medication pattern of interest, and the drug and disease under study determine the time window.

Objective Antibiotics are the most commonly prescribed drugs used by children. Excessive and irrational use of antibiotic drugs is a world-wide concern. We performed a drug utilization study describing the patterns of antibiotic use in children aged 0-19 years between 1999 and 2005 in the Netherlands. Methods We used IADB.nl, a database with pharmacy drug dispensing data covering a population of 500,000 people and investigated all prescriptions of oral antibiotic drugs ( Conclusion The use of antibiotic drugs in treating children in the Netherlands is comparable to that in other northern European countries. Broad-spectrum antibiotics were prescribed more frequently than recommended by the guidelines and increased during our study period. Initiatives to improve guideline-directed antibiotic prescribing are strongly recommended.