Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005–2012

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Highlights

  • From 2005–2012, antidepressant (ATD) use increased markedly in all studied countries.

  • In 2012, ATD prevalence was 1.6% (US), 1.1% (UK), 1.0% (DK), 0.6% (NL) and 0.5% (DE).

  • Increase was greatest in 10−14 year olds (NL, UK) and 15−19 year olds (DK, DE, US).

  • SSRIs were most popular in DK (81.8% of all ATDs), and tricyclics in DE (23.0%).

  • Top-ranking drugs were citalopram (DK, NL), fluoxetine (DE, UK) and sertraline (US).

Abstract

Following the FDA black box warning in 2004, substantial reductions in antidepressant (ATD) use were observed within 2 years in children and adolescents in several countries. However, whether these reductions were sustained is not known. The objective of this study was to assess more recent trends in ATD use in youth (0−19 years) for the calendar years 2005/6–2012 using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). In a repeated cross-sectional design, the annual prevalence of ATD use was calculated and stratified by age, sex, and according to subclass and specific drug. Across the years, the prevalence of ATD use increased from 1.3% to 1.6% in the US data (+26.1%); 0.7% to 1.1% in the UK data (+54.4%); 0.6% to 1.0% in Denmark data (+60.5%); 0.5% to 0.6% in the Netherlands data (+17.6%); and 0.3% to 0.5% in Germany data (+49.2%). 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. While SSRIs were the most commonly used ATDs, particularly in Denmark (81.8% of all ATDs), Germany and the UK still displayed notable proportions of tricyclic antidepressant use (23.0% and 19.5%, respectively). Despite the sudden decline in ATD use in the wake of government warnings, this trend did not persist, and by contrast, in recent years, ATD use in children and adolescents has increased substantially in youth cohorts from five Western countries.

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)

  • D.J. Breland et al.

    Determinants of mental health service use among depressed adolescents

    Gen. Hosp. Psychiatry

    (2014)
  • R.C. Kessler 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)
  • E. Acquaviva 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)
  • C.J. Bachmann 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)
  • H. Bergen 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)
  • B.T. Blak et al.

    Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates

    Inform. Prim. Care

    (2011)
  • D.A. Brent

    Antidepressants and pediatric depression – the risk of doing nothing

    N. Engl. J. Med.

    (2004)
  • S.H. Busch et al.

    Pediatric antidepressant use after the black-box warning

    Health Aff.

    (2009)
  • G.R. Byck

    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)
  • C.U. Correll et al.

    Prescribing of psychotropic medications to children and adolescents: quo vadis?

    World Psychiatry

    (2013)
  • S. Dalsgaard et al.

    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.

    (2013)
  • M. Dörks et al.

    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

    (2013)
  • C.A. Fontanella et al.

    Factors associated with antidepressant adherence for medicaid-enrolled children and adolescents

    Ann. Pharmacother.

    (2011)
  • C.A. Fontanella et al.

    Trends in psychotropic polypharmacy among youths enrolled in Ohio medicaid, 2002−2008

    Psychiatr. Serv.

    (2014)
  • R.A. Friedman

    Antidepressants׳ black-box warning – 10 years later

    N. Engl. J. Med.

    (2014)
  • Hazell, P., Mirzaie, M., 2013. Tricyclic drugs for depression in children and adolescents. The Cochrane Database of...
  • Health and Social Care Information Centre, 2015. Prescriptions dispensed in the community. Statistics for England,...
  • F. Hoffmann et al.

    Differences in sociodemographic characteristics, health, and health service use of children and adolescents according to their health insurance funds

    Bundesgesundheitsblatt Gesundh. Gesundh.

    (2014)
  • F. Hoffmann et al.

    Trends in antidepressant prescriptions for children and adolescents in Germany from 2005 to 2012

    Pharmacoepidemiol. Drug Saf.

    (2014)
  • H. Hölling et al.

    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.

    (2014)
  • L. Horsfall et al.

    Identifying periods of acceptable computer usage in primary care research databases

    Pharmacoepidemiol. Drug Saf.

    (2013)
  • L.J. Kalverdijk et al.

    Use of antipsychotic drugs among Dutch youths between 1997 and 2005

    Psychiatr. Serv.

    (2008)
  • L.Y. Katz et al.

    Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults

    Can. Med. Assoc. J.

    (2008)
  • A.S. Kesselheim et al.

    Strategies and practices in off-label marketing of pharmaceuticals: a retrospective analysis of whistleblower complaints

    PLoS Med.

    (2011)
  • W. Kondro et al.

    Drug company experts advised staff to withhold data about SSRI use in children

    Can. Med. Assoc. J

    (2004)
  • B.T. Kurian et al.

    Effect of regulatory warnings on antidepressant prescribing for children and adolescents

    Arch. Pediatr. Adolesc. Med.

    (2007)
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