During the 6-year study period, rates of children and adolescents enrolled in Medicaid who received at least 1 clonidine prescription nearly doubled. Our study documents for the first time unexpected and increasing trends of clonidine use by demographic characteristics particularly in adolescents. Poor medication adherence has been well documented in adolescent patients with chronic conditions.12
This is particularly concerning when considering the significant side effects of rebound HTN and sympathetic overdrive associated with sudden discontinuation of clonidine.1,3
Moreover, adverse drug effects of clonidine for adolescents may be profoundly different from adults because of the dynamic changes that occur during this vital period of growth and development but have not been systematically evaluated. Further study to evaluate the interplay of medication adherence, medication use, and adverse effects in pediatric patients treated with clonidine should have particular focus on adolescents given the trends identified in this study.
The majority of clonidine prescriptions in our study were for the treatment of simple and complex ADHD, not for its FDA-approved indication, HTN. Thus, well before FDA’s approval to use clonidine for the treatment of ADHD, it was frequently prescribed “off-label” for children and adolescents for the treatment of ADHD. We have previously demonstrated common off-label use of other antihypertensive medications in children despite the availability of on-label alternatives in the same class of antihypertensive medications.13
Although off-label use of prescription medications for pediatric patients may be common, in the absence of adequate safety and efficacy studies in children and adolescents, off-label prescribing adds an additional layer of complexity with concern for unforeseen potential short-term and longterm adverse drug effects. Thus, a systematic strategy to closely monitor for adverse drug effects in pediatric patients receiving chronic pharmacotherapy prescribed both on-label and off-label should be developed and implemented.
During the 6-year study period, clonidine was increasingly prescribed for children with complex ADHD, whereas use in children with simple ADHD stayed constant across years. This is important when considering that most children in our study with ADHD (simple or complex) who received clonidine prescription were additionally prescribed stimulant or nonstimulant ADHD medications in the same year. Taken together, this concomitant use of clonidine and ADHD medications (stimulant and nonstimulant) in the majority of children in this study raises concerns about polypharmacy.
Adult studies have demonstrated increased probability of adverse drug effects associated with polypharmacy. 14–16
Side effects of clonidine (drowsiness, fatigue, hypotension, and cardiac arrhythmias) and drug interactions have been previously described.2,17,18
Stimulant and nonstimulant ADHD medications have their own side effects in children and adolescents including but not limited to cardiovascular effects such as arrhythmias and mood disorders such as increased suicidal ideation. Patterns of polypharmacy identified in our study need to be further evaluated for potential drug interactions and patient outcomes. Given that the majority of clonidine and ADHD medications were prescribed by the same physician specialty in this study, it seems that adverse drug effect and drug interaction monitoring efforts could be targeted and accomplished within specialties.
Finally, we found that across years the leading prescribers of clonidine for children were psychiatrists. However, we describe unexpected trends in clonidine prescribing where PCPs (adult and pediatric) were increasingly prescribing clonidine whereas clonidine prescribing by specialists such as psychiatrists was decreasing. Given the cross-sectional nature of this analysis, we cannot determine which specialty initiated clonidine prescription for each child. Hence, it is plausible that PCPs are refilling clonidine prescriptions for their pediatric patients and not necessarily initiating treatment decisions. Nevertheless, the pattern of increased role of PCPs in chronic disease management such as ADHD demonstrated in this study is practical, since primary care would be a more reasonable setting for long-term drug monitoring efforts and evaluation of patient outcomes. Yet how this is currently accomplished or evaluated in the primary care setting is unknown and warrants further investigation.