From Recommendation to Implementation—Recommendations of the German Clinical Practice Guideline and Choice of Antidepressants for Children and Adolescents: Analysis of Data From the Barmer Health Insurance Fund

The effectiveness of selective serotonin reuptake inhibitors (SSRIs) and the lack of effectiveness of tricyclic antidepressants in minors have been confirmed for 20 years (1). For Germany, data show that the prescribing practice for antidepressants across different diagnoses is adapting only slowly (2).

In 2013 the first German Clinical Practice (S3) guideline for the treatment of depression in children and adolescents was published. The guideline recommends pharmacological treatment with SSRIs beginning in the 9th year of life in cases where psychotherapy is not possible or is not sufficient. The present study investigates on the basis of health insurance data the prescribing behavior practice regarding antidepressants for depressed minors of physicians in private practice before and after publication of the S3 guideline.

Material and methods

Data source

The Barmer health insurance fund made available anonymized data from insurance members as regards ICD-10 diagnoses and medication data for ACT (Anatomic Therapeutic Chemical Classification System) codes for the years 2005–2018.

Our analysis is based on person years—that is, the sum of individual years during which children and adolescents aged 8–17 years were insured with the Barmer fund in the respective calendar years before the guideline was introduced (2008–2012) and after its publication (2014–2018) (a total of 7,658,629 person years).

Case definitions

First prescription of an antidepressant: contact with doctor for a diagnosis of depression (ICD-10 F32 or F33) in the relevant calendar year (index year) and prescription of an antidepressant; no antidepressant prescription in the preceding three calendar years nor contacts with doctor for other psychiatric ICD-10 diagnoses (F0, F2, F30, and F31). Antidepressants were identified on the basis of the ATC codes. Guideline recommended antidepressants: ATC codes N06AB03 (fluoxetine), N06AB04 (citalopram), N06AB06 (sertraline), N06AB10 (escitalopram). N06AB (for example, paroxetine), N06AA (for example, amitriptyline), N06AF (for example, tranylcypromine), N06AG (for example, moclobemide) and N06AX (for example, mirtazapine) were considered to be antidepressants not recommended by the guideline.

Statistical analysis

Absolute and relative frequencies of prescribed antidepressants before and after publication of the guideline and their difference were calculated with 95% confidence intervals (normal distribution approximation). A multiple linear regression model for the frequency of guideline recommended prescriptions relative to a) the calendar year, b) an indicator variable of whether the calendar year fell before or after the introduction of the guideline (= 0 for 2008–2012, = 1 for 2014–2018), and c) an interaction between these two variables was determined, in order to check for a possible jump or a steeper increase after the guideline.

We used SAS version 9.4 (SAS Institute, Cary, NC, USA) and R3.5.1 (R Foundation for Statistical Computing, Vienna, Austria) for all our calculations.

Results

The number of first prescriptions issued rose from 3184 before guideline publication to 5902 after its publication (factor 1.9). Over the same time periods, the numbers of children with contact to a doctor for a diagnosis of depression increased by a factor of 1.6. 71% of all children with first prescriptions were girls, 91% were older than 13.

The proportion of guideline recommended antidepressant prescriptions rose from 55.6% in the time period before the guideline to 72.1% in the period after the guideline (Table). The biggest increase was seen for fluoxetine (14.9%). Prescriptions of antidepressants not recommended by the guideline sank from 44.4% to 28.0%. The Figure shows relative prescription frequencies of guideline recommended antidepressants (dots) with 95% confidence intervals and by regression model (lines) by calendar year. Before the S3 guideline was published the proportion of guideline recommended prescriptions rose by 1.6 percentage points every year, and by 2.7% percentage points every year after it had been published (P<0.05).

Figure

Proportion of guideline recommended antidepressants by years with confidence interval

Table

Proportion of guideline recommended and non-guideline recommended antidepressants by substance groups before and after the guideline

Discussion

The analyzed health insurance fund data showed a rise in first prescriptions. The proportion of guideline recommended antidepressants increased after the guideline had been published. This trend also existed before the guideline, but the increase after publication reached significance. Overall it should be considered that contraindications or comorbidities may be an obstacle to the prescription of SSRIs; a completely guideline conform prescribing practice is therefore not expected for any point in time (particularly relevant comorbidities were, however, excluded from our analysis).

The safety concerns regarding suicidal ideation and behavior after antidepressant medication in minors published by the health authorities of several countries since October 2003 triggered a temporary fall in prescriptions of all antidepressants (2). Compared with the numbers in 2008–2012, the absolute number of prescriptions of antidepressants to minors under observation almost doubled in 2014–2018, with the proportion of guideline recommended antidepressants increasing from 55.6% to 72.1%.

Possible alternative explanation models for the bigger increase in guideline conform antidepressants in 2014–2018 that might be discussed are:

Groundbreaking scientific publications and internationally published guidelines. SSRIs have been recommended as the medication of choice in children and adolescents for 20 years, and since 2005 this has been the case especially for fluoxetine (3);

The costs of antidepressants: as early as in 2009, treatment with a guideline recommended SSRI (average cost of all SSRIs: 0.49€/defined daily dose) was more economical than with a tricyclic antidepressant (average cost 0.50/defined daily dose) (4) (with the exception of escitalopram).

Licensing changes: fluoxetine was approved in 2006 for the treatment of moderate and severe depressive episodes in minors and to date remains the only licensed SSRI for this indication (2).

Supply shortages: for the relevant medications our research did not identify any supply shortages for the years 2009–2018 (5).

The crucial factors of influence for the prescription of SSRIs as the medication of choice pre-date both observation periods. The bigger increase in prescription numbers according to guideline recommendations could be explained with the publication of the S3 guideline.

Viola Obermeier*, Michael Frey*, Rüdiger von Kries, Gerd Schulte-Körne
The Institute of Social Paediatrics and Adolescent Medicine, The Division of Epidemiology, Ludwig-Maximilians-University Munich (Obermeier, von Kries)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University Munich, (Frey, Schulte-Körne),

*The two authors share first authorship.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 14 October 2020, revised version accepted on 18 January 2021.

Translated from the original German by Birte Twisselmann, PhD.

Cite this as
Obermeier V, Frey M, von Kries R, Schulte-Körne G: From recommendation to implementation—recommendations of the German Clinical Practice Guideline and choice of antidepressants for children and adolescents: analysis of data from the Barmer health insurance fund. Dtsch Arztebl Int 2021; 118: 215–6.
DOI: 10.3238/arztebl.m2021.0126

References

1. Park R, Goodyer I: Clinical guidelines for depressive disorders in childhood and adolescence. Eur Child Adolesc Psychiatry 2000; 9: 147–61

2. Schröder C, Dörks M, Kollhorst B, et al.: Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011. Pharmacoepidemiol Drug Saf 2017; 26: 170–9

3. Dolle K, Schulte-Körne G: The treatment of depressive disorders in children and adolescents. Dtsch Arztebl Int 2013; 110: 854–60

4. Schwabe U, Paffrath D: Arzneiverordnungs-Report 2015. Springer 2015

5. Lieferengpässe für Humanarzneimittel. www.bfarm.de/DE/Arzneimittel/Arzneimittelzulassung/Arzneimittelinformationen/Lieferengpaesse/_functions/Filtersuche_Formular.html?queryResultId=null&pageNo=0 (last accessed on 17 September 2020).