Background
Attention-deficit/hyperactivity disorders (ADHD) is one of the frequent neurodevelopmental disorders among children and adolescents. A recent population-based study in Germany showed a stagnating trend in the period between 2009 and 2016 [
1]. In 2016, the prevalence amounted to 4.3% among children between 5 and 14 years [
1]. The clinical guideline by the German Society for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy recommends as an initial step a non-pharmacological therapy, including psychosocial and psychotherapeutic interventions [
2]. Accordingly, pharmacological intervention should only be initiated if a non-pharmacological therapy was unsuccessful. The first-line pharmacological treatment are stimulants (methylphenidate and amphetamines); the non-stimulants, atomoxetine and recently licensed guanfacine are second-line treatment options. Methylphenidate, available since 1954, is (by far) the most frequently prescribed stimulant for ADHD with atomoxetine being the second most frequently prescribed substance [
3].
There has been controversy regarding ADHD over decades [
4]. In particular, overdiagnosis and overmedication with stimulants were the subject of intense debate [
5]. Previous studies reported increasing trends in prescription of both stimulants and non-stimulants in earlier years in Germany. Garbe et al. showed a dramatic increase in methylphenidate use in the period of 1990 to 2010; in this period prescription of methylphenidate increased by a factor 187 [
6]. The prescription prevalence of methylphenidate on the population level doubled from 0.54% in 2000 to 1.1% in 2007 among children and adolescents [
7]. Abbas et al. also observed a prevalence increase of both, methylphenidate and atomoxetine prescriptions from 2004 to 2012 [
8]. The prescription prevalence of atomoxetine increased from 0% in 2004 to 2.1% in 2008 [
8]. Due to an increasing trend in using stimulants the Federal Joint Committee (G-BA, “Gemeinsamer Bundesausschuss”) – the German regulatory agency for statutory health insurance – issued several prescription restrictions over the period of 2009 to 2014 [
9]. In 2009 the stimulant prescription was restricted for preschool children. For school-aged children stimulants should only be prescribed as a second treatment option after a first-line nonpharmacological therapy without sufficient clinical improvement. In 2010 the G-BA extended the directives by restricting prescription of stimulants to certain specialist groups. There was a sign of stagnation or even a slight downward trend in prescription prevalence of methylphenidate between 2009 and 2014 [
3]. Less is known about prescription patterns for other recently introduced stimulants, dexamfetamine and lisdexamfetamine and a non-stimulant guanfacine.
The aim of the study was to examine the secular trends and regional variations in pharmacotherapy of children and adolescents with ADHD. In particular, we were interested in the effect of restrictions issued by the G-BA on prescription prevalence and prescribing patterns.
Discussion
Using the nationwide prescription data we examined the trends and regional variations in pharmacotherapy of ADHD among children and adolescents in Germany. Overall, we observed a decreasing trend in prescription prevalence of stimulants and non-stimulants over the period 2009 to 2016. In addition, there were regional variations in prescription.
Previous research in Germany observed rising trends in use of stimulants [
12]. The G-BA responded to these trends in using pharmacological treatment in Germany by issuing several prescription restrictions of stimulants [
9]. The first restrictions were introduced in 2009 and extended in 2010. The aim of these directives was to avoid overuse of pharmacological therapy, in particular among those children not needing pharmacological treatment (e.g. preschool children and children with a possible false positive diagnosis). Indeed, we observed an age-related association in prescriptions of all substances and a downward trend for methylphenidate, the most frequently prescribed stimulant and atomoxetine. In terms of age, the proportion of younger children (in particular preschool children) with a prescription was very low, which in addition to the G-BA restrictions can also be explained by the clinical guideline of the German Society for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, which recommends first a non-pharmacological therapy, including psychosocial and psychotherapeutic interventions in children younger than 6 years and a pharmacotherapy in children between 3 and 6 years in exceptional cases. In terms of time trends we observed a slight decline in methylphenidate prescriptions in the period of 2009 to 2013 and a pronounced drop in 2014 with a subsequent decline thereafter. Atomoxetine, a non-stimulant, also displayed a downward trend. Bachmann et al. observed a stagnation in total ADHD medication use among children and adolescents younger than 19 years between 2008 and 2012 [
13]. In another study, Bachmann et al. reported first evidence of a decline in medication use among children and adolescents by comparing prescription prevalence in 2009 and 2014 [
3]. Both studies did not differentiate across various substances. Finally, a recently published study reported similar trends in medication use among children (≤16 years) in a 10-year period of 2008 to 2018 [
14]. This study was based on a relatively small sample of children and adolescents (
n = 33,192). All five substances were included in the study, however, only overall trends for ADHD medication were reported without differentiation of specific substances.
We observed the only increase in prescription prevalence of amphetamines. In 2013 licenced lisdexamfetamine showed a nearly 4-fold increase within the first 3 years (2013, 1.7%; 2016, 6.5%). In the year of license lisdexamfetamine was the third most frequently prescribed medication. In 2014 it was already the second most frequently prescribed medication. Dexamfetamine prescriptions increased by a factor 2.6 from 2012 (0.26%) to 2016 (0.69%). However, overall, the proportion of children receiving amphetamine prescriptions was low. Of note, the introduction of new medications and an increase of amphetamine prescriptions did not result in an overall increase of children prescribed medications.
One possible explanation for declining prescription trends would be the decrease in prevalence of ADHD. However, in the same period of time we did not observe a decrease in prevalence of ADHD [
1]. The prevalence of ADHD in the same study population of 5 to 14 years old children and adolescents showed a stagnating trend between 4.1% in 2009 and 4.3% in 2016 [
1]. In conclusion, the declining trends may be explained by the above-mentioned restrictions issued by G-BA.
Regionally we observed distinct patterns, which have not been described previously. Methylphenidate was more commonly prescribed in Western than in Eastern federal states. A similar finding was seen for lisdexamfetamine although the regional pattern was not so clear. On the contrary, atomoxetine prescriptions were more common in Eastern federal states. The reasons for these variations are not known and need to be explored. Grobe et al. examined regional differences in methylphenidate use on a district level and observed a high correlation between ADHD prevalence and medication use (r = 0.84) [
15]. We did not observe such a correlation on the level of federal states (Spearman’s rho = 0.046,
p = 0.86). Unfortunately, a regional analysis on a district level is not possible as this information is not available in the dataset due to the current data protection regulations. One possible explanation for regional variations in prescription prevalence is the availability of various physician groups. For instance, the density of pediatric psychiatrists and psychotherapists is higher in Western than Eastern federal states [
16]. This is also supported by the fact that the prescription prevalence of the lately introduced amphetamines, lisdexamfetamine and dexamfetamine, was highest in both Hanseatic cities Bremen and Hamburg. Both cities have a high density of pediatric psychiatrists and psychotherapists as compared to other regions.
We observed a shift towards increasing proportion of physician groups specialized in psychiatry and psychotherapy prescribing stimulants. Whereas in 2009 the most frequent physician group prescribing methylphenidate were pediatricians, this pattern changed gradually over years. In the last year of observation (2016), the most frequent physician group prescribing methylphenidate were pediatric psychiatrists and psychotherapists. The proportion of pediatricians showed a slow decrease over years. However, in 2016 every third patient with ADHD still received a prescription from a pediatrician. The proportion of GPs prescribing methylphenidate showed a more rapid decline; e.g. in 2016 only every 15th patient with ADHD received a prescription from this physician group. Overall, we observed changes in prescribing patterns which can be attributed to the second directive of the G-BA issued in 2010. The G-BA restricted prescriptions to certain physician groups. The prescription of stimulants by pediatricians and GPs was only allowed in exceptional cases.
Strengths and limitations
We used the nationwide outpatient drug prescription data of all statutory health insured individuals covering 87% of the total German population. The dataset does not contain information on individuals insured privately. The latter have a higher socio-economic status, which was associated with a lower risk of ADHD [
17]. We cannot rule out possible differences in use of pharmacological treatment between statutory and privately insured children. On the other side, the dataset may yield the complete picture of stimulant and non-stimulant prescriptions as nearly 99% of all ADHD diagnoses (and pharmacological treatment) occur in outpatient care [
15]. Furthermore, SHI-physicians code diagnoses according to the ICD-10. We used the code F90 “hyperkinetic disorders” to identify children and adolescents with ADHD. Since there are differences in diagnostic criteria based on the ICD-10 – which codes hyperkinetic disorders – and the Diagnostic and Statistical Manual of Mental Disorders (DSM) – which codes ADHD – the risk of misclassification in our study may not be ruled out.
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