Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005–2012
Introduction
The safety of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression in children and adolescents has been a subject of much concern and debate (Brent, 2004, Friedman, 2014). In October 2004, the U.S. Food and Drug Administration (FDA) issued a “black-box”, now termed “boxed” warning, indicating an increased risk of suicidal ideation/suicidal behavior in children and adolescents treated with SSRIs (Friedman, 2014). This followed similar action in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency (MHRA), and was soon followed by similar warnings by other regulatory bodies (e.g. European Medicines Agency (EMA) warning against the use of SSRIs in youths<18 years, August 2005). Within 2 years after these warnings, the use of antidepressants (ATDs) decreased markedly in children and adolescents in Canada, the UK and the USA (Bergen et al., 2009, Busch and Barry, 2009, Katz et al., 2008, Kurian et al., 2007, Olfson et al., 2008). However, such decreases occurred mostly for youth diagnosed with less severe depression while psychotherapy use increased substantially (Valluri et al., 2010). Whether diminished ATD use has persisted is not known.
A decade after government warnings, the controversy continues on the evidence for the risk of suicidal events associated with ATD use in children and adolescents. Notably, the majority of ATDs are not licensed in youth less than 18 years of age, and thus are commonly prescribed “off-label”. Considering the broader international context in which there is a significant influence of cultural and health system factors on psychotropic medication use in general (Schomerus et al., 2014, Steinhausen, 2013), information on how ATD use has evolved over recent years in different countries is needed. While there are a few studies assessing multinational patterns of psychotropic medication use in youth (Zito et al., 2006), to date, there is no recent multinational epidemiological data on trends in ATD use in children and adolescents. Single country comparisons (Dörks et al., 2013, Hoffmann et al., 2014, Pottegard et al., 2014, Wijlaars et al., 2012, Zoega et al., 2009) are often hampered by dissimilar study methods (e.g. different timespans or age groups). The objective of this study is to assess more recent trends in ATD use in youth (0−19 years) using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). We also assess patterns of antidepressant use according to age group, sex, ATD subclass and entity.
Section snippets
Denmark
To perform this study we used the Danish Registry of Medicinal Products Statistics (RMPS). The registry is a national prescription database on all outpatient pharmacy-dispensed prescription medications in Denmark (5.53 million inhabitants) and is updated monthly. Each prescription record contains detailed information on the drug dispensed (incl. ATC code). With the use of an estimation of the underlying population (denominator), the prevalence can be calculated.
Germany
We used claims data of the single
Results
In 2012, the number of youths receiving ATD per studied population of youths between 0−19 years were as follows: Germany: 6849/1,414,623, Denmark: 11,774/1,203,817, Netherlands: 790/131,954, United Kingdom: 8680/827,906, and United States: 1667/105,188.
Across seven years from 2005/6 through 2012 (Figure 1), the annual prevalence of ATD use for children and adolescents increased in all studied cohorts as follows: USA cohort: 1.3% to 1.6% (+26.1%), UK cohort: 0.7% to 1.1% (+54.4%), Denmark
Discussion
The major findings of this study are as follows: 1) From 2005/6 through 2012, the prevalence of ATD use in children and adolescents increased substantially in cohorts from five Western countries, with both absolute and relative increases being most pronounced in the UK and in Denmark. 2) Regarding age groups, the relative growth was greatest for 15−19 year olds in Denmark, Germany and UK cohorts, and for 10−14 year olds in Netherlands and US cohorts. 3) While SSRIs were the most commonly used
Role of funding source
No funding was secured for this study.
Contributors
Dr. Bachmann conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted. Prof. Aagard acquired, analyzed and interpreted data, revised the manuscript critically, and approved the final manuscript as submitted. Mehmet Burcu acquired, analyzed and interpreted data, revised the manuscript critically, and approved the final manuscript as submitted. Prof. Glaeske acquired, analyzed and interpreted data, revised the manuscript critically, and
Conflict of interest
Christian Bachmann has received lecture fees from Actelion, Novartis, and Ferring as well as payment from BARMER GEK and from AOK for writing book chapters. He has served as a study physician in clinical trials for Shire and Novartis. Gerd Glaeske and Falk Hoffmann are active on behalf of a number of statutory health-insurance companies (BARMER GEK, DAK, TK, and various corporate health-insurance funds) in the setting of contracts for third-party payment. Lise Aagaard has received traveling
Acknowledgments
The authors are grateful to the insurance funds, databases and government agencies that provided the data on antidepressant use.
References (52)
- et al.
Determinants of mental health service use among depressed adolescents
Gen. Hosp. Psychiatry
(2014) - et al.
National comorbidity survey replication adolescent supplement (NCS-A): III. Concordance of DSM-IV/CIDI diagnoses with clinical reassessments
J. Am. Acad. Child Adolesc. Psychiatry
(2009) - et al.
Psychotropic medication in the French child and adolescent population: prevalence estimation from health insurance data and national self-report survey data
BMC Psychiatry
(2009) - et al.
Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012
Dtsch. Arzteblatt Int.
(2014) - et al.
Trends in prescribing and self-poisoning in relation to UK regulatory authority warnings against use of SSRI antidepressants in under-18-year-olds
Br. J. Clin. Pharmacol.
(2009) - et al.
Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates
Inform. Prim. Care
(2011) Antidepressants and pediatric depression – the risk of doing nothing
N. Engl. J. Med.
(2004)- et al.
Pediatric antidepressant use after the black-box warning
Health Aff.
(2009) A comparison of the socioeconomic and health status characteristics of uninsured, state children׳s health insurance program-eligible children in the united states with those of other groups of insured children: implications for policy
Pediatrics
(2000)- et al.
Prescribing of psychotropic medications to children and adolescents: quo vadis?
World Psychiatry
(2013)
Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study
J. Child Adolesc. Psychopharmacol.
Antidepressant drug use and off-label prescribing in children and adolescents in germany: results from a large population-based cohort study
Eur. Child Adolesc. Psychiatry
Factors associated with antidepressant adherence for medicaid-enrolled children and adolescents
Ann. Pharmacother.
Trends in psychotropic polypharmacy among youths enrolled in Ohio medicaid, 2002−2008
Psychiatr. Serv.
Antidepressants׳ black-box warning – 10 years later
N. Engl. J. Med.
Differences in sociodemographic characteristics, health, and health service use of children and adolescents according to their health insurance funds
Bundesgesundheitsblatt Gesundh. Gesundh.
Trends in antidepressant prescriptions for children and adolescents in Germany from 2005 to 2012
Pharmacoepidemiol. Drug Saf.
Psychopathological problems and psychosocial impairment in children and adolescents aged 3−17 years in the German population: prevalence and time trends at two measurement points (2003−2006 and 2009−2012): results of the KiGGS study: first follow-up (KiGGS wave 1)
Bundesgesundheitsblatt Gesundh. Gesundh.
Identifying periods of acceptable computer usage in primary care research databases
Pharmacoepidemiol. Drug Saf.
Use of antipsychotic drugs among Dutch youths between 1997 and 2005
Psychiatr. Serv.
Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults
Can. Med. Assoc. J.
Strategies and practices in off-label marketing of pharmaceuticals: a retrospective analysis of whistleblower complaints
PLoS Med.
Drug company experts advised staff to withhold data about SSRI use in children
Can. Med. Assoc. J
Effect of regulatory warnings on antidepressant prescribing for children and adolescents
Arch. Pediatr. Adolesc. Med.
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