From Vince Boehm:
Methylphenidate, Amphetamine Salts Show Similar Cardiac Risks in Children With ADHD
July 20, 2009 — Exposure to methylphenidate and amphetamine salts [note: In North America methylphenidate is most commonly known as the brand name Ritalin. Brand names of the drugs that contain amphetamine include Adderall, Vyvanse, and Dexedrine. – Vince] shows a similar risk for cardiac emergency department (ED) visits for children and adolescents with attention-deficit/hyperactivity disorder (ADHD), according to results of a large reported in the July issue of Pediatrics.
“Although the evidence base for the cardiac effects of central nervous system stimulants that are used for the treatment of…ADHD is still unsatisfactory, concerns have resulted in a Food and Drug Administration (FDA) mandate for medication guides to alert patients to potential cardiovascular risks and adverse psychiatric symptoms,” write Almut Gertrud Winterstein, PhD, from the Department of Pharmaceutical Outcomes and Policy at the College of Pharmacy, and the Department of Epidemiology and at the College of Public Health and Health Professions, University of Florida, Gainesville, and colleagues.
They write that clinical trial data have shown evidence of cardiac adverse effects, including increases in heart rate and blood pressure and case reports of cardiac sudden death, in children exposed to stimulants. In addition, the authors published a recent cohort study of more than 50,000 children with ADHD that showed a 20% increased risk for cardiac ED visits for all stimulants combined.
Because few data comparing the safety profile of individual stimulant agents are available, this study sought to compare the risk for cardiac events in patients using methylphenidate or amphetamine salts. “Information on the comparative safety of the 2 most prevalent substances that are used to treat ADHD would aid in the assessment of the risk/benefit of pharmacologic treatment and inform treatment decisions,” write the study authors.
The investigators used claims data from the Florida Medicaid fee-for-service program, which represented 2,131,953 children and adolescents. They analyzed data from 30,576 patients newly diagnosed with ADHD who were between the ages of 3 and 20 years, enrolled between July 1994 and June 2004, and newly prescribed methylphenidate (n = 18,238) or amphetamine salts (mixed amphetamine salts or dexamphetamine, n = 17,175).
Dr. Winterstein and her team defined cardiac events as the first ED visit for cardiac disease or symptoms “because they occur more frequently than hospital admissions or cardiac death and provided the best power to detect even subtle differences between drugs.”
The investigators used prescription drug claims to determine the use of central nervous system stimulants and an adjusted time-dependent Cox proportional hazard model to compare the risk between current users of the study drugs, as well as former users.
At the end of the study, results showed a total of 456 ED visits by the patients for cardiac reasons during 52,783 years of follow-up. After adjusting for differences in covariates, the risk for cardiac ED visits was similar among current users of methylphenidate and amphetamines (adjusted [HR], 1.01; 95% confidence interval [CI], 0.08 – 1.28).
Likewise, periods of former use between the study drugs showed a similar risk (adjusted HR, 0.95; 95% CI, 0.73 – 1.25).
Switching patterns that might indicate intolerability of a specific drug were also similar between groups, with 4890 (26.8%) of the patients who initially received methylphenidate switching to amphetamine during the study period and 2947 (23.9%) of the initial amphetamine users switching to methylphenidate.
“This is the first study to report comparative safety data of stimulants in a cohort of >30,000 children and adolescents,” report the study authors. However, “Concerns that amphetamines might have a larger propensity to cause cardiac relative risk estimates did not support a pronounced risk difference between the 2 drug classes.” could not be confirmed in this study [and] both unadjusted and adjusted
Limitations of the study include its observational design, its reliance on claims data (making it prone to misclassification), and no consideration for drug dosing. “Comparative dosage studies that weigh psychotropic effectiveness against potential cardiac adverse effects would be valuable in guiding treatment options,” write the investigators.
They add that this study also included no comparison of stimulants and atomoxetine [aka Strattera – Vince] “because the latter was approved only in 2002. Atomoxetine is not categorized as a central nervous system stimulant and it is unclear whether it offers a safer alternative.”
Overall, the authors conclude, “Additional population-based studies that address manifestation of serious cardiac risk factors are needed to inform psychiatric treatment decisions.”, especially after long-term use, dosage comparisons, and interactions with preexisting
This study was funded in part by the Florida Department of Health, Agency for Healthcare Administration. One study author has received partial funding by a grant from the Agency for Healthcare Research and Quality. The other study authors have disclosed no relevant financial relationships.