The influence of using methylphenidate on coming up psychiatric disorders in children with attention deficit/hyperactivity disorder
Date Issued
2009
Date
2009
Author(s)
Chen, Chiou-Fu
Abstract
Background: Attention deficit/hyperactivity disorder (ADHD) is the most common developmental neuropsychiatric disease in children. CNS stimulants especially methylphenidate (MPH) are major therapeutic agents for ADHD. ADHD often occurs with other psychiatric illness therefore the treatment with neuropsychotropic agents is common. Although numerous studies strongly support the efficacy of MPH in symptom reduction, its role in the risks for substance use or occurring psychiatric adverse events has been the interesting topics for MPH. Up to now; there have been no information about the long-term use of neuropsychotropic agents to children with ADHD in Taiwan. The pharmacoepidemiology data for ADHD patients is important for clinical practice and medical policy.bjectives: To describe the trends of neuropsychotropic agents used to treat children with ADHD over 10 years of time and to investigate the impact of long-term effect of MPH use on coming up other psychiatric disorder with ADHD.ethods: This study was a pharmacoepidemiology study. The medical claim from outpatient settings with a diagnosis of ADHD and patients’ age under 18 years old were retrieved from a subset database of National Health Insurance database (NHIRD), i.e., the LHID2005, from 1997 to 2007. Descriptive analysis on the treated prevalence rate and the trend in the use of neuropsychotropic agents especially MPH for ADHD patients was conducted. The second part of our study was a retrospective cohort study. Children with new onset of ADHD from 1999 to 2003 were included as ADHD group; they were further divided into two subset group (ADHD-M and ADHD-N) according to the MPH usage in the observation period. The non-ADHD group of the same age range and sex to the ADHD group was retrieved from LHID2005 of patients other than the ADHD group. Time to bipolar disorder come up was the primary endpoint of this study, and time to depression, dysthymia, anxiety, conduct disorder and oppositional defiant disorder come up were secondary endpoint. Survival analysis was conducted by using time dependent Cox proportional hazard regression model to evaluate potential confounding factors by univariate analysis. Potential confounding factors were used to adjust hazard ratio of MPH use model in multivariate analysis.esults: The rate of outpatient services for ADHD increased from 0.05% in 1997 to 1.27% in 2007 (β =0.25，p<.0001). The male to female ratios for patients in the retrieved ADHD medical records were in the range of 2.6:1 to 5:1 over the years, and the mean age of patients in the medical records was 8.5±3.2 years old. The rate of outpatient services in all age groups for ADHD increased from 1997 to 2007, and 6-9 age group increased at most. The most commonly used neuropsychotropic agents was methylphenidate (MPH), the prescription rate of MPH increased significantly (β= 0.078, p<0.0001) from 42.6 to 64 per 100 medical records from 1997 to 2007. ADHD patients in 12-15 age group had the highest prescription rate of MPH. Percentage of patients under MPH treatment in male ADHD patients was higher than those in female ADHD patients. The prescription rate of immediate-release (IR) MPH (β = -0.04, p<.0001) decreased with a significantly increased from 2004 to 2007 in osmotic release oral system (OROS) MPH (β = 0.46, p<.0001；β = 0.85, p<.0001). Other than MPH, antidepressants (4.4%-8.2%) were the highest prescription rate of psychotropic medications and antipsychotics (3.9%-5.2%) were the second. The prescription rate of SSRIs (β= 0.11, p<0.0001) increased from 0.8% to 3.7%, however, significantly decrease in the prescription rate of TCAs (β= -0.16, p<0.0001) from 4.4% to 1.1% was found in the same period. The prescription rate of atypical antipsychotics (β= 0.18, p<0.0001) increased significantly (0% to 3%) with a decrease (4.1% to 1.0%) in typical antipsychotics (β = -0.10, p<0.0001) from 1997 to 2007. A total of 2109 new onset ADHD patients from 1999 to 2003 were identified and 8414 matched controls were randomly selected. The ADHD group had a mean age of 7.3 year old and 79.8% were males. There were higher risk of occurring bipolar disorder, depression, dysthymia, anxiety, conduct disorder and oppositional defiant disorder in group of ADHD-M to ADHD-N by calculating the odds ratio. After multivariate analysis and adjusted by univariate, MPH (p<0.05) use had a relationship with bipolar disorder and oppositional defiant disorder in ADHD patients.onclusions: Results of this study indicated that not only the rate of outpatient services for ADHD patients but also the rate of medication therapy in ADHD patients in Taiwan increased significantly from 1997 to 2007. MPH was the most used neuropsychotropic agents to children with ADHD in Taiwan as expected. The impact of long-term effect of MPH use on coming up bipolar disorder and oppositional defiant disorder is truly existed. Although the mechanism of this effect still unknown, it should be used cautiously on clinical practice.
Subjects
ADHD
methylphenidate
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