Psychopharmacological treatment in children and adolescents with autism spectrum disorders in Germany
Introduction
The term “autism spectrum disorders” (ASD) summarises a range of pervasive developmental disorders, including (amongst others) the diagnostic categories of DSM-IV “autistic disorder”, “Asperger disorder/syndrome” and “pervasive developmental disorder, not otherwise specified” (Wing, Gould, & Gillberg, 2011) and the ICD-10 diagnoses “childhood autism” (ICD-10 code: F84.0), “atypical autism” (ICD-10 code: F84.1), “Asperger's syndrome” (ICD-10 code: F84.5), “other pervasive developmental disorders” (ICD-10 code: F84.8) and “pervasive developmental disorder, unspecified” (ICD-10 code: F84.9). Core features of ASD are social interaction deficits, impaired communication and language skills and stereotyped or repetitive behaviours and interests; about 50% of ASD patients have mild up to severe intellectual disabilities (Charman et al., 2011).
In a systematic review of thirty-two surveys from the years 1966–2001, the prevalence of ASD was 0.7–72.6 per 10,000 individuals, with a median prevalence (calculated from studies published between 1992 and 2001) of 12.7 per 10,000 (Williams, Higgins, & Brayne, 2006). ASD show a marked male preponderance, with the male-to-female ratio ranging from about 4:1 in ASD to 10:1 in high-functioning autism or Asperger's syndrome (Fombonne, 2009). Up to 70% of patients with ASD exhibit psychiatric comorbidities, e.g. ADHD, anxiety disorders, conduct disorder, schizophrenia or depression, which are persistent from childhood to adolescence (Simonoff et al., 2008, Simonoff et al., 2013). Sleep disorders and epilepsies are also more frequent in individuals with ASD (Bolton et al., 2011, Souders et al., 2009).
Despite large efforts to identify effective pharmacological substances for the treatment of the core symptoms of ASD (e.g. Hampson, Gholizadeh, & Pacey, 2012), to date no pharmacological treatment for these symptoms is available. However, for the aforementioned comorbidities, psychopharmacological treatment is recommended in current guidelines (e.g. DGKJP, 2007; for an overview of current treatment strategies: McPheeters et al., 2011). Nevertheless, the level of evidence for the majority of those treatments is only moderate (Hurwitz et al., 2012, McPheeters et al., 2011, Williams et al., 2010). This can be attributed to different factors, e.g. scarcity of well-designed clinical studies in this population (Reichow, 2012) or non-effectiveness of substances that are effective in non-ASD patients (e.g. King et al., 2009, Williams et al., 2010). Besides, a significant proportion of ASD patients receive also complimentary or alternative medication (Anagnostou & Hansen, 2011).
In Germany, no medication is approved especially for treatment of autistic children; in the USA, the FDA has approved risperidone for the treatment of irritability in autistic children and adolescents (FDA, 2006).
Regarding the pharmacoepidemiology of ASD, there exists a small, but growing body of literature: starting with the study of Aman, van Bourgondien, Wolford, and Sarphare (1995), there is now a variety of studies that have been performed in difference settings (inpatient, outpatient and both) and that are based on different information sources (e.g. internet surveys or healthcare insurance data sets) and differing samples with respect to age ranges, diagnoses and sample sizes (see Table 1). The to date largest study (Mandell et al., 2008) found in a nationally representative sample of sixty thousand six hundred forty-one US-American Medicaid patients with ASD a prevalence of psychotropic medication of 56% during a 1-year period (2001). In that study, the substance group most frequently prescribed was antipsychotics (31%), followed by antidepressants (25%) and stimulants (22%). With only few exceptions (Baghdadli et al., 2005, Memari et al., 2012), the vast majority of studies on psychopharmacology use in ASD have been conducted in the USA, so there is a significant lack of data for European countries. This lack of data is regrettable, especially as prescription patterns in child and adolescent psychiatry tend to show quite significant differences between Europe and the USA (Zito et al., 2008). Also, there is a scarcity of studies reporting longitudinal trends in ASD pharmacoepidemiology.
The main objective of this study was therefore to assess cross-sectionally psychopharmacological medication in child and adolescent outpatients with diagnosed ASD with respect to age and sex. The second goal was to evaluate time trends in medication patterns in this patient group.
Section snippets
Database and identification
We conducted a cross-sectional study using claims data of the statutory health insurance company Gmünder ErsatzKasse (GEK) for the year 2009. In the corresponding year, the GEK insured 1.8 million persons living in all regions of Germany.
We included all individuals aged up to 24 years that were insured at least one day in all four quarters of 2009. Due to this criterion, the vast majority of our population at risk was continuously insured throughout the whole year.
Subsequently, we identified
Results
A total of four hundred fifty-eight thousand five hundred and five children and adolescents aged 0–24 years were insured at least one day in all four quarters of 2009. Of them, 50.4% were male and the mean age was 13.5 (SD: 6.8) years.
Discussion
The prevalence of ASD found in this study (0.37% in males and 0.12% in females) and especially the male/female ratio stands in line with findings of other studies (Fombonne, 2009) and reflects the mix of low- and high-functioning ASD diagnoses in our sample.
Regarding neuropsychiatric comorbidities, we found a prevalence of 64.8%, which is comparable to the results of Simonoff et al. (2008), who reported a comorbidity rate of 70.8% in a thoroughly characterised, population-derived sample of
Conclusion
This naturalistic study furnishes evidence that the proportion of children and adolescents with diagnosed ASD treated with psychotropic drugs has grown considerably in Germany over the least years. The most frequently prescribed substance classes were antipsychotics and ADHD drugs, with methylphenidate and risperidone being the most frequently prescribed substances. Compared with pharmacoepidemiologic data from the USA, the proportion of ASD patients treated with psychotropic drugs appears to
Conflicts of interest
CB has received speaker honoraria from Ferring, Novartis and Actelion and has acted as a clinical study investigator for Shire Pharmaceuticals. TM has received a travel grant from Medice. IKB has received speaker honoraria from Medice. All other authors declare that they have no conflicts of interest.
Role of the funding source
No funding source.
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