Use of attention deficit/hyperactivity disorder pharmacological treatment following the public discussion on cardiovascular safety and the introduction of medication guides for central nervous system stimulants and atomoxetine

Intense public discussion and some regulatory action occurred in 2005-2007 following a safety signal regarding the cardiovascular (CV) risk of central nervous system stimulants (stimulant) and atomoxetine. Our objective was to describe changes in stimulant utilization and pre-treatment electrocardiography (ECG) screening after this safety signal.;A time-series design including 96 months (2001-2008) of Florida Medicaid claims data was used to describe changes in trends of stimulant utilization. Joinpoint regression models were used to detect the number of change points, to estimate the magnitude of change in monthly outcome trends, and to test comparability of trend change(s) among patient subgroups.;Both the initial and maintenance daily dose declined by 6 milligram (mg) methylphenidate equivalent dose from a previously steady dose of 26 mg after Canada withdrew one stimulant product (Adderall XR) in 02/05; the trend rebounded to a consistently lower dose (23 mg) after the remarketing of Adderall XR and a debate in the U.S. over issuing a boxed warning on stimulant CV safety in early 2006. The monthly initiation rate increased by 3.9% (95% CI -1.0, 9.1) after the boxed warning debate, but started to decline by 2.4%(-3.6,-1.2) after patient medication guides (MedGuides) released in 02/07. Monthly ECG screening increased by 3.2% (2.3, 4.2) after Canada withdrew Adderall XR and further increased by 13 % (4.2, 23) after the American Heart Association recommended pre-stimulant-treatment ECG. The decline in treatment initiation differed by patient age, presence of mental comorbidities or disability; the reduction in treatment intensity, however, did not show significant difference among subgroups. A more pronounced increase in ECG use was observed among patients with less complicated mental conditions or patients who were diagnosed by psychiatrists.;Practitioners reacted to stimulant CV safety signal with immediate reduction in dosing and an increase in preventive screening, affecting however only a marginal proportion of patients. Utilization rates started to drop only after release of MedGuides and affected only initiation but not chronic use of stimulants. Change in stimulant use was not significant among vulnerable subgroups, such as young patients, patients with mental comorbidities or disability. Clinical consequences of these changes are uncertain.