Nearly 1 in 9 children have been diagnosed with attention deficit hyperactivity disorder, and most take prescription stimulant drugs for years to calm their behaviors and help them focus in school. While drug manfacturer clinical trials clearly demonstrate that these drugs — which include methylphenidate (Ritalin) and amphetamine/dextroamphetamine (Adderall) — work to alleviate symptoms, very few were designed to investigate the long-term safety of these drugs, according to a new study conducted by Boston Children’s Hospital researchers.
The study authors emphasized that this doesn’t mean ADHD drugs pose safety risks but that the initial approval trials — which made them available to thousands of children for long-term use — largely ignored the possibility of safety issues.
They identified 32 clinical trials on the 20 ADHD drugs approved by the US Food and Drug Administration and found that only five of the trials focused on drug safety and that each drug was tested on an average of 75 patients before getting FDA approval. The average length of each trial was just four weeks. The study was published Wednesday in the journal PLOS One.
“This is a wake up call for what’s lacking in the drug approval process and what we want to see in the future,” said study co-author Dr. Kenneth Mandl, chair of biomedical informatics at Boston Children’s Hospital. “Our findings are particularly troubling since these drugs are so widely used and used for years, not weeks.”
Experts convened at a forum called the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use recommended in 1994 that drugs intended for chronic use in non-life-threatening conditions, such as ADHD, should be tested in a minimum of 300 to 600 patients for at least six months, in a minimum of 100 patients for at least one year, and in about 1,500 patients total before they’re approved for widespread use.
Mandl and his colleagues also found that the FDA requested six follow-up safety studies from drug manufacturers to assess long-term safety risks but that only two of these studies were ever conducted.
“Some concerns raised by the FDA focused on cardiac side effects and issues around growth in children, but these side effects appear to be very rare,” said study lead author Dr. Florence Bourgeois, a pediatrician in the department of emergency medicine at Boston Children’s. “Overall these drugs are very safe, but at the time they were approved, such safety information wasn’t available.”
Parents should have a conversation with their child’s pediatrician before deciding whether or not to use prescription drugs to treat ADHD, Bourgeois recommended, so they can understand what’s known about the long-term benefits and risks — and what’s not known due to lack of research. “This can help them make a more informed decision,” she said.
They can also ask about behavioral treatments, which some studies suggest can be as effective as medications in managing symptoms of the condition.Deborah Kotz can be reached at firstname.lastname@example.org. Follow her on Twitter @debkotz2.