In addition to the fluoxetine, on other serotonin reuptake inhibitors commonly used in the EU (duloxetine, venlafaxine, sertraline, paroxetine and fluoxetine) are indicated in children. Duloxetine was first approved in August 2004 for stress urinary incontinence (Yentreve) via the centralized procedure. Duloxetine was approved for major depressive disorder in December 2004, for diabetic peripheral neuropathic pain in July 2005 and for generalized anxiety disorder in July 2008. The European Medicines Agency is asking Eli Lilly and Company to conduct a study on the use and off-label use of duloxetine in Europe. This study was designed to assess the frequency of use and off label use of duloxetine, in particular in adolescents and children, and to compare this with the use of other similar antidepressants. The study has utilized longitudinal, patient-level routine healthcare data from 4 different databases in 3 European countries, including Pedianet. 

The study population comprised all persons (all ages) registered in the databases (General Practice Research Database GPRD (UK), Health Search Database (HSD)-THALES (Italy), PEDIANET (Italy), Integrated Primary Care Information database (IPCI) (Netherlands)), with at least one year of valid data. The study period started on August 1, 2004 until December 31st 2009 or later, as feasible (may vary by database depending on the coverage period and lag time of the databases). Duloxetine was the drug of primary interest. In order to compare the percentage of off-label prescribing three comparator drugs had been chosen. These were venlafaxine, paroxetine and fluoxetine. There were 4 outcome-parameters: 

a) The age and sex-specific prevalence of use of duloxetine, venlafaxine, paroxetine and fluoxetine in each country (number of users/1000 persons per month and year in source population) 
b) The age and sex-specific incidence rate of new users of the study drugs by calendar year and age (over total population) in each country (number of new users/1000 PY in source population) 
c) For each prescription (refills included) the following parameters will be described: 
- Age 
- Sex 
- Indication for use (at time of prescription) 
- Daily dose 
d) For each new study drug user we assessed the following parameters: 
- Indication for use (at cohort entry) 
- Second line: It was assessed (at cohort entry) whether study drugs were second or first line antidepressants (use of other antidepressants in year prior) 
- Off-label use 
To perform the analyses (Incidence rates of new users and Prevalence of study drug use) it was used SAS.

Partecipants and Collaborations


Department of Medical Informatics, MI&EUR BV 
Erasmus University Medical Center, Rotterdam. 


Project leader
Miriam Sturkenboom, PharmD, PhD 
Erasmus University Medical Center ( 
Departments of Medical Informatics and Epidemiology 


Katia Verhamme, MD, PhD 
Geert ‘t Jong, MD, PhD 
Erasmus University Medical Center ( 
Departments of Medical Informatics 

Giampiero Mazzaglia, MD, PhD (SIMG, HSD) 
SIMG (Societa’ Italiana di Medicina Generale) ( 

Gianluca Trifiro’ MD, PhD (Erasmus MC) 

G. Picelli, Pedianet 


Eli Lilly and Company