Naturalistic Pharmacotherapy Compliance among Pediatric Patients with Attention Deficit/Hyperactivity Disorder: a Study Based on Three-Year Nationwide Data

In the Diagnostic and Statistical Manual of Mental Disorders 5^th edition (DSM-5), attention-deficit/hyperactivity disorder (ADHD) is included in the category of neurodevelopmental disorders (1). This seemingly supports previous studies’ reports that ADHD shows chronic progression and that symptoms persist into adulthood in approximately 50% of individuals (2-7). Compared to typical adults, those with ADHD have a higher rate of substance abuse, lower education levels, and lower occupational ability (8-10). In this regard, considering the chronic progression of ADHD and the socioeconomic costs of the disease itself, long-term continued treatment is essential. However, administration of long-term treatment is difficult in practice. Of the various treatment methods that might be applicable in the long term, drug treatment is the main choice, although compliance thereto is low. Although the results of previous studies differ, due to methodological differences, 3-year long-term drug compliance for pediatric ADHD patients is approximately 30% (11-16). In particular, there are large differences in the 6-month drop-out rate, at 20% (17), 42.4% (18), and more than 80% (19), depending on the drop-out criteria. Although the treatment discontinuance rate is high, it is also not true that all pediatric patients receive medicinal treatment after diagnosis of ADHD. In a previous study (20), the proportion of patients starting drug treatment after ADHD diagnosis was 69%, and studies in the United States using a birth cohort or a local community sample have found drug treatment rates of 59%–73% (21-23).

Various methods are used to assess continuation of drug treatment, including the medication possession ratio or “MPR” (24-26) and gap days (27). In a previous study on a small sample (18), authors suggested that it was not appropriate to apply the same criteria for drug treatment in psychiatry, particularly pediatric ADHD, as those applied to other chronic diseases, such as hypertension. At the same time, authors proposed the need for verification in a larger sample.

Hence, following from the previous study, in this study, we analyzed 3-year treatment continuation rates in a large group, using data from the Health Insurance Review and Assessment Service (HIRA), and identified differences in compliance, based on the conventional criteria for treatment compliance.

Unlike the present study, there are almost no large-scale, nationwide, long-term drug treatment studies on pediatric ADHD patients. This is because there are not many countries like South Korea or Taiwan that have adopted a single medical insurance system for the whole country, including more than 97% of the total population. Because the medical guarantee system is a product of a country’s unique institutional and historical characteristics, one cannot easily compare according to types of medical guarantee system. Therefore, there is a lack of existing data against which the current study results can be compared.

In a study analyzing drug continuance among 40,052 children with ADHD in the southern United States, based on the Medicaid claims database, when applying a 1-month gap, 47.4% of the study population showed drug continuance after 6 months, and 26.9% showed continuance after 12 months (15). When applying a 30-day gap (1-month gap) in the present study, the drug continuance rate after 1 year was 10.4%. In a study by Winterstein et al. (15), when using a 3-month gap, drug continuance was 49.9% after 1 year, 32.8% after 2 years, 17.2% after 5 years, and 15.4% after 9 years. The naturalistic treatment compliance of 47.4% after 1 year in the present study was similar to the result obtained by Winterstein et al. (15) (49.4%), when using a 3-month gap. Although there will be other confounding factors affecting these differences, it should be first be noted that the study subjects in the two studies were recruited from different types of insurance systems. Specifically, Winterstein et al.’s (15) study subjects were drawn from the Medicaid population (low-income group and minorities) in one region in the United States. Our study subjects subscribed to a medical insurance group representing the total population of Korea; in this group, 99.19% of the affiliates of the insurance group are self-funding. A study by Wong et al. (16), using the United Kingdom’s General Practice Research Database (GPRD), defined treatment persistence as an interval between claims that spans less than 6 months. The drug continuance rate was 83% after 1 year, 54% after 2 years, 36% after 3 years, 24% after 4 years, 22% after 5 years, and 17% after 6 years. In the present study, we adopted the criteria of Wong et al. (16), but the treatment compliance rate was 47.35% after 1 year, 34.13% after 2 years, and 23.09% after 3 years; these rates were lower than those obtained by Wong et al. (16). These differences could be due to the fact that the United Kingdom’s medical system is socialist, whereas in Korea, the insurance system is funded both by individuals and the government. In a retrospective analysis of the medical records of 300 pediatric ADHD patients from a single Korean university hospital (18), naturalistic treatment continuance was found to be 47.3% after 1 year, 29.3% after 2 years, and 20.0% after 3 years. This is similar to the results of the present study, which used data from the whole population. Although there are differences, to some extent, results from international studies and those of the present study show that long-term treatment compliance in pediatric ADHD patients decreases rapidly over time.

Hodgkins et al. (28) used data from 4,909 individuals in the Netherlands, who had been newly diagnosed with ADHD and commenced treatment. Defining adherence as MPR > 0.8, they reported an adherence rate of 64% for the first 3 months, and 44% after 1 year. In other words, their drop-out rates of 36% and 56% after 3 months and 1 year, respectively, were similar to the results of the present study, at 34.8% and 53.6%. In addition, there are studies on drop-out rates at around 6 months (3, 17, 19), but there are almost no studies on treatment compliance patterns during the first 6 months, even though this is the critical period in which the highest proportion of patients drop out. In the present study, when we performed a detailed analysis of the drop-out rates at 1-month intervals over the first 6 months, known to be the critical period for treatment continuance, we found that approximately one fifth of the total patient group dropped out within 1 month of starting drug treatment. The possible explanation of these high early drop-outs might be lack of enough awareness among parents, children, and physicians. Kim et al. (29) suggested parent educational program at or before initiation of pharmacotherapy might increase the long term treatment compliance. There was a positive correlation between the length before pharmacotherapy initiation after diagnosis of ADHD, and treatment compliance at 6-month after initiation of pharmacotherapy. Also recent qualitative study with 25 parents of children with ADHD and 18 practitioners highlighted the importance of parenting programs (30). Considering that ADHD is a condition with a high risk of chronicity, there is a need to provide practice guidelines by performing analysis and establishing measures to account for attrition in the first 6 months, and particularly in the first 4 weeks after commencement of drug treatment.

Although the present study used a large amount of data obtained from the entire national population, this presented some limitations. First, when using data from HIRA, because the necessary consent for use of personal information has not been received, it is impossible to confirm information for several useful parameters, including parents’ education, socioeconomic status, and area of residence. Second, because it is not possible to confirm data for non-medicinal treatment due to the nature of the HIRA data, it was not possible to investigate treatment continuance rates for these treatment methods.

In spite of these limitations, the present study is significant, as it is the first to investigate naturalistic pharmacotherapy continuance rates for the first 3 years for ADHD patients, using the entire 6–18-year-old South Korean population.