Drug therapy for migraine in children by pediatricians in Germany – what role do discount agreements play?

Migraine and other headaches represent a significant health problem in children and adolescents and impair quality of life. Although they are frequently associated with adults, headache disorders such as migraine and tension-type headaches often begin in childhood or adolescence (Blankenburg et al., 2019). Migraine in children and adolescents, in particular, presents a diagnostic and therapeutic challenge, as young patients may inadequately describe their symptoms or exhibit atypical symptoms (Silveira Bianchim et al., 2024). The guidelines of the German Migraine and Headache Society and the Society for Neuropediatrics recommend ibuprofen in a single dose of 10 mg/kg body weight as the first-line treatment for acute headaches in children occurring as part of migraine or tension-type headaches. Paracetamol in a single dose of 15 mg/kg body weight is recommended as a second-line treatment. For migraine attacks that do not respond to analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs), triptans should be used in adolescents (Diener et al., 2019). In rare exceptional cases or for individual indications, triptans are also used off-label in children under 12 years of age. Acetylsalicylic acid is generally not recommended in Germany for children under 12 years of age due to the risk of Reye's syndrome (Mund et al., 2015). There is a significant research gap in the knowledge of how acute migraine therapies are actually prescribed in children and adolescents.

> Katsuki et al. untersuchten die Migränetherapie bei Kindern und Jugendlichen in Japan und stellten fest, dass 99% der Patienten im Alter von 6–11 Jahren und 91% der Jugendlichen im Alter von 12–17 Jahren NSAR erhielten. Zudem erhielten 9% der Jugendlichen Triptane, entweder als Monotherapie oder zusätzlich zu NSAR (Katsuki et al., 2024). In Deutschland gibt es bisher nur wenige Studien zur Anwendung und Häufigkeit der verschiedenen Migränemedikamente bei Kindern und Jugendlichen. Folglich sind Daten zur tatsächlichen Nutzung dieser Therapien in der Praxis, einschließlich altersabhängiger Unterschiede in den Verordnungsgewohnheiten, rar.
The aim of this study is to investigate the acute treatment of migraine in German pediatric practices, including prescribed medications, dosages, and dosage forms.

methods
This study used data from the IQVIA Disease Analyzer database. This database has been previously described in the literature and is considered representative of outpatient care in Germany (German private practices) (Rathmann et al., 2018). It contains data from approximately 3,000 general and specialist practices in Germany, including basic demographic information, diagnoses, and prescriptions.
The study included children aged 2–12 years who were diagnosed with migraine (ICD-10: G43) by one of 250 practicing pediatricians in Germany between January 2015 and December 2024. The study endpoint was the proportion of children who received at least one prescription for migraine medication on the day of diagnosis. The analysis included all medications prescribed with a migraine diagnosis, including NSAIDs, acetylsalicylic acid, triptans, and topical Mentha piperita.
For NSAIDs, the proportions of the different active ingredients (i.e., ibuprofen, metamizole, paracetamol), dosage forms (i.e., regular tablets, orodispersible tablets, suspensions, and others), and dosages (i.e., <200 mg, 200 mg, 400 mg, >400 mg) were further investigated.
The present cross-sectional study included descriptive analyses to present the proportions without conducting hypothesis tests.

Results
A total of 21,315 children (1,539 aged 2–5 years and 19,776 aged 6–12 years) were diagnosed with migraine for the first time between 2015 and 2024.
168 (10.9%) of children aged 2–5 years and 4,620 (18.3%) of children aged 6–12 years received a prescription for migraine medication. The most frequently prescribed drug was ibuprofen (75.4%) in the 2–5 year age group and 75.9%) in the 6–12 year age group), followed by paracetamol (19.8%) in the 2–5 year age group and 11.2%) in the 6–12 year age group). Other therapies were rarely prescribed (Fig. 1).
Figure 2 shows the distribution of ibuprofen doses. In the 2–5 year age group, exclusively doses of <200 mg (36.0 mg/day) and 200 mg (64.0 mg/day) were prescribed. The 200 mg dose was also most frequently prescribed in the 6–12 year age group (66.7 mg/day), followed by 400 mg (20.5 mg/day) and <200 mg (9.2 mg/day). Higher doses (>400 mg) were rarely prescribed (3.6 mg/day).
Among children aged 2–5 years who received an ibuprofen prescription, 68.2% received ibuprofen as a suspension, 16.3% as rectal suppositories, and 15.5% as orodispersible tablets. In the 6–12 year age group, the suspension (36.3%) was the most frequently prescribed dosage form, followed by orodispersible tablets (31.8%) and regular tablets (29.9%) (Fig. 3).

discussion
This study provides insights into the care management of migraine in pediatric patients in Germany based on real-world data collected between 2019 and 2023. The treatment concept for acute migraine attacks in children includes general measures such as local cooling, rest, shielding from stimuli, and, if possible, sleep. These measures are often sufficient, so that drug therapy is not even necessary (Baglioni et al., 2024). This concept of non-pharmacological treatment could not be considered in the present study, which focuses on pharmacotherapy.
Pharmacological therapies were prescribed more frequently for older children aged 6–12 years than for younger children aged 2–5 years. This discrepancy may reflect pediatricians' reluctance to prescribe medications to very young children. Furthermore, pain attacks in this age group are often shorter and can often be controlled through parental care and the general measures mentioned above.
Among the prescribed active ingredients, ibuprofen was the most frequently used treatment in both age groups, followed by paracetamol. This is consistent with current German guidelines.
The preference for ibuprofen in our study is consistent with its established efficacy and safety profile in pediatric migraine treatment (Jeric et al., 2018).
In both age groups, the 200 mg dose was most frequently prescribed. Higher doses (400 mg) were prescribed more frequently in older children, likely reflecting differences in body weight and tolerability. Importantly, doses above 400 mg were rarely prescribed, consistent with guidelines recommending cautious dosing in pediatric populations to minimize adverse effects.
In terms of dosage forms, suspensions were most commonly prescribed for younger children, presumably due to their ease of administration in this age group. In contrast, children aged 6–12 years were more likely to receive orodispersible tablets, but also regular tablets, reflecting their greater ability to take solid dosage forms. Orodispersible tablets offer several advantages for children, particularly in the treatment of conditions such as migraines. They dissolve quickly on the tongue without the need for water, making them ideal for children who have difficulty swallowing traditional tablets or capsules, or who are reluctant to take medication. This form is particularly beneficial in situations where water is not readily available. Due to their ease of use and often pleasant taste, they are generally a popular dosage form in pediatric medicine. Swallowing large tablets is avoided and anxiety can be reduced, which also improves treatment adherence.
In addition, their compact shape makes them easy to transport and administer in a variety of settings—such as school, travel, or outdoor activities. For younger children or those with swallowing difficulties, orodispersible tablets eliminate the risk of choking or aspiration associated with swallowing whole tablets or capsules. Taste-masking technologies are also often used to make the bitter taste of active ingredients like ibuprofen more pleasant. By addressing common medication administration challenges in childhood, orodispersible tablets improve the overall experience for children and caregivers and promote effective and consistent medication adherence (Preis 2015; Alyami et al., 2018; Comoglu & Dilek Ozyilmaz, 2019; Chinwala, 2020).
Many children aged 6–12 years in the present study received ibuprofen as an oral suspension. This can present some challenges. For example, it can be difficult for parents to measure the exact dose using a dosing cup. Dosing is often based on the child's weight and age, which can lead to uncertainty if these factors are not carefully considered. Some children dislike the taste of ibuprofen suspension, which can lead to resistance or refusal to take the medication. Older children need to take a larger amount of the suspension, which can be uncomfortable, especially in cases of migraine-related nausea (Yin et al., 2014; Barnett & Bhatt, 2020). Finally, there is a risk of gagging or choking if the medication is administered too quickly, especially in infants or young children. For these children, suppositories are a suitable alternative.
When comparing the prescription frequency of ibuprofen suspension and orodispersible tablets, it is important to consider the health policy situation. In Germany, rebates from pharmaceutical companies to statutory health insurance funds (discount agreements) are a common strategy to control pharmaceutical spending. These agreements serve as a complementary measure to price regulation, especially when the latter does not sufficiently reduce drug costs (Vogler et al., 2012; Rodwin, 2021).
In our study, we observed that ibuprofen suspension was prescribed more frequently than the orodispersible tablet. A key factor behind this prescribing trend may be the existence of discount agreements, especially since the manufacturers of ibuprofen suspensions are involved in discount agreements, and physicians and pharmacists are encouraged to prescribe and dispense cheaper preparations due to the generally strained economic situation in the healthcare system. The frequent use of suspensions could therefore be based on cost-effectiveness. This illustrates how financial incentives and agreements between manufacturers and payers can influence prescribing behavior.
Further evidence for this hypothesis is the fact that in 2015, orodispersible tablets were the most commonly prescribed form for the treatment of pediatric migraine, even though suspensions were available at that time. Furthermore, orodispersible tablets will continue to be the most common form of ibuprofen for privately insured patients in 2024. This could be because both physicians and parents prefer orodispersible tablets when they can decide without the influence of discount contracts.
Oral suspensions are more suitable for children under 5 years of age, as the 200 mg orodispersible tablets cannot be divided into equivalent doses, and smaller children would otherwise exceed the weight-based ibuprofen dose of 10 mg/kg. Paracetamol and ibuprofen are also available as rectal suppositories for young children and are commonly used in this age group.
Although both paracetamol and ibuprofen are effective and well-tolerated treatment options (Pavithra et al., 2020), ibuprofen has sometimes been considered an overall better alternative for migraine pain relief (Teleanu et al., 2016). Professional experience may play an important role in physicians' decisions to prescribe paracetamol or ibuprofen.
Regarding other therapies observed in the present study, the low prescription rates of metamizole and Mentha piperita suggest that their use remains limited, possibly due to regulatory or practical constraints and limited evidence in the pediatric population (Ruiz et al., 2007; Murtey et al., 2024).
The strengths of this study include its large sample size and comprehensive database. These findings could have significant implications for clinical practice and research.
However, some limitations must be considered. First, the study does not consider non-pharmacological treatment approaches, which play a crucial role in the management of pediatric migraine. Second, the lack of data on the severity and impact of migraine limits the ability to fully contextualize treatment decisions.
Thirdly, there was no information on the diagnostic
Migraine diagnostic methods are available, so it is possible that the diagnoses documented by pediatricians were already made by a specialist without the pediatrician's involvement in the diagnostic process. Finally, other headache types, such as tension headaches, were not examined in this study.

Conclusion

Apparently, orodispersible tablets are the preferred dosage form for children, but they cannot always be prescribed due to discount agreements. Study results underscore the need to develop age-appropriate therapeutic strategies to improve migraine care in the pediatric population.