Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

In this analysis of a nationally representative audit of office-based providers between 2004 and 2008, changes were observed in the market share for stimulant therapies and for atomoxetine. However, FDA advisories regarding the potential risks of ADHD medications had little discernible effect on their use. These results are important given how common ADHD is in the United States and how frequently it is treated with pharmacologic therapies such as those examined.

Although some FDA communications may have immediate or substantial effects on medication use (31), there are several reasons that others may have limited impact (32–34). First, given that the primary goal of regulatory communications is to convey information rather than change behavior, assessments of changes in prescription drug use or other health care use after an advisory provide a limited window through which to assess whether the advisory was successful. It is possible that the advisories were successful in communicating the uncertainties about ADHD therapies but insufficient to change the overall balance of the treatment decisions that providers and patients faced. For example, instead of reducing their prescribing, physicians may have monitored patients more closely. Second, providers’ lack of response to these advisories may reflect their doubts about the seriousness or reliability of the information upon which they were based. Indeed, a recent retrospective study that used data from four health plans suggested that ADHD drugs do not increase risks of cardiovascular problems among children and young adults (19). Additional factors that may have limited the impact of these FDA advisories include physician knowledge of drug risks that preceded the relevant warnings, changes in the advertising and promotion of these drugs to consumers and providers, and the failure of the advisories to reach their intended audiences or to communicate risk information effectively (35,36).

Furthermore, although we were unable to detect differences in ADHD medication prescribing when rates of prescribing before and after the FDA advisories were compared, it is possible that the FDA advisories nevertheless had an impact on prescribing behavior. Lag effects or interventions that are rolled out in multiple stages (for example, via a series of high-profile reports in the press) may limit the application of time series analyses (37). High-profile news reports and scientific investigations may have preceded FDA advisories, and in some cases, publicity regarding risks may have continued to build after the FDA warnings were issued (38). Even though changes in medication use were not closely timed to FDA advisories, the overall declines in use of Adderall and atomoxetine that we observed and the concomitant increase in the use of other stimulants may reflect shifting assessments of safety.

We also found paradoxical effects of some advisories, such as the association between the February 2005 Adderall PHA and increases in Adderall market share among specialists. These inconsistencies may reflect the fact that other influences on prescribing, such as therapies entering and leaving the marketplace or industry marketing and promotion, may have undermined any effect that the FDA communications might have had. In the case of declines in atomoxetine use that occurred after the Adderall advisories, it is possible that these declines represented “spillover” effects or were due to the influence of scientific or media reports about atomoxetine that occurred during the same period (39).

Although we did not find a statistically significant effect of the advisories on use of specialty care, the modest increase in overall rates of specialty care that we identified is consistent with other reports regarding care patterns for ADHD (7,40). Shifts toward greater specialization of labor associated with increasing drug risks are consistent with theory and also have been evident in other settings, as in the case of antidepressants, when FDA advisories regarding the risk of suicidality among children were accompanied by shifts from primary care physicians to specialists (29,30). Increases in Adderall market share among specialists after the Adderall PHA may in part reflect the referral of patients to specialist care or an increase in follow-up visits among those already on Adderall.

Our analysis has several limitations and raises additional questions for future research. First, segmented regression analysis depends upon a sufficient number of time points and may be sensitive to how the segments are defined. In light of this, we conducted sensitivity analysis that adjusted the length of the time segments (for example, before and after the Adderall PHA in February 2005), and these yielded substantively similar findings. Second, shifts in care on the basis of patients’ sex, socioeconomic status, disease severity, and comorbidities may not have been captured by our methodology. These advisories may also have had spillover effects in the treatment of adult populations that were not captured by our analysis. Third, the advisories may have shifted the rate at which families fill written prescriptions, but these changes were not captured in the NDTI. Fourth, our focus was on office-based diagnosis and pharmacotherapy of children and adolescents, and thus we do not have data regarding the variety of nonpharmacologic treatments that play an important role in ADHD treatment, such as diet, alternative medications, cognitive and behavioral therapies, or social and educational interventions. Future studies might also examine whether FDA advisories had a larger effect among patients with relevant comorbid conditions, such as cardiovascular disease or other mood disorders, that might increase risks. Finally, this analysis was limited to one audit of office-based encounters, and our findings should be corroborated via other office-based audits, such as the National Ambulatory Medical Care Survey.

Overall rates of ADHD pharmacologic treatment of children and adolescents were stable between 2004 and 2008, despite a series of FDA advisories concerning the risks of common ADHD medications. Although the market shares for Adderall and atomoxetine declined over this period, we did not identify any consistent association between FDA advisories and the use of these drugs. Continued assessments of consumer and provider responses to FDA advisories may help identify factors associated with patient and physician responsiveness and will be important for informing future communications about medication risks.

This work was supported by the Agency for Healthcare Research and Quality (RO1 HS0189960). Dr. Dusetzina receives funding through a Ruth L. Kirschstein-National Research Service Award (T32MH019733-17). Dr. Dorsey is supported by the Robert Wood Johnson Physician Faculty Scholars Program. Dr. Huskamp is supported by a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. The study is based in part on data obtained under license from IMS Health, Inc. (National Disease and Therapeutic Index, 2004–2010). The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IMS Health, Inc., or any of its affiliated or subsidiary entities.

Ms. Kornfield and Dr. Alexander are consultants for IMS Health, Inc. Dr. Dorsey has received research support from Prana Biotechnology, Lundbeck, and Google. He is a consultant for Lundbeck and Medtronic and has stock options in ConsultingMD. The other authors report no competing interests.