Whether or not you agree that Attention Deficit Hyperactivity Disorder (ADHD) is a “real” disease, the ADHD epidemic has grown from 150,000 cases in 1970, to an estimated 3 to 7 percent of school-age children. Some estimates put the rate as high as 15 percent of all school-age children and while it is difficult to get an exact figure what is clear is that the diagnosis of ADHD is on the rise.
What is ADHD?
The medical community defines ADHD as a neurological brain disorder that manifests as a persistent pattern of inattention and/or hyperactivity/impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. While ADHD is classified as a chronic disease, it is treatable. That’s good news for sufferers of the condition and of course for the pharmaceutical industry. The most commonly prescribed medications for ADHD are stimulants such as methylphenidate (Concerta® from ALZA and Ritalin® from Novartis), and amphetamine (Dexedrine® from GlaxoSmithKline and Adderall® from Shire Pharmaceuticals). In 2002, the first and only non-stimulant medication atomoxetine (a selective norepinephrine reuptake inhibitor - Strattera® from Eli Lilly), was approved by the FDA for the treatment of ADHD. What is also interesting about Strattera®, is that it is the first drug designed to treat Adult Attention Deficit Disorder (ADD).
Stop fidgeting and listen
Whereas we all might be guilty of fidgeting during meetings, of interrupting our colleagues’ conversations and of losing our keys from time to time - a long and persistent history of restless, impulsive, or inattentive behavior may be a sign of Adult ADD. This is especially true if these behaviors have existed since childhood and result in problems at work, home, and/or in social settings.
So as more and more of our children and now perhaps some of our colleagues are being diagnosed as having ADHD, drug use to treat the condition is on the rise – and predictably, to anyone who was paying attention to all this, side effects and adverse events that may be related to these powerful drugs are also on the rise.
When things go wrong
On December 17, 2004 Eli Lilly, the manufacturer of Strattera® announced that it had added a bolded warning to the product label saying that that the drug should be discontinued in patients with jaundice or laboratory evidence of liver injury. This label change was a result of two reported cases of severe liver injury out of the more than 2 million patients who have taken the medication since approval. Both patients have recovered with normal liver function after discontinuing the medication.
Then on February 9, 2005, Health Canada ordered that the drug Adderall XR® be taken off pharmacy shelves after learning that Adderall® and the once-daily version Adderall XR® had been linked to 20 sudden deaths and 12 strokes worldwide. The drug is marketed in Canada by Shire BioChem Inc.
On the same day, the FDA released a press release stating that “FDA has been in close consultation with the Canadian authorities regarding the basis for their action. FDA does not feel that any immediate changes are warranted in the FDA labeling or approved use of this drug based upon its preliminary understanding of Health Canada’s analyses of adverse event reports and FDA’s own knowledge and assessment of the reports received by the agency.”
In their response, Shire, while having to agree with Health Canada's request, said that it "strongly" disagreed with the conclusions drawn by Health Canada and was considering "appropriate responsive action."
Over 700,000 Americans use Adderall® and its extended release counterpart, Adderall XR®, accounting for $759 million sales the United States last year. In Canada about 11,000 patients take the drug accounting for $10 million.
How can a drug be safe for use in America and be considered too dangerous for sale to Canadians?
Many individuals believe that the FDA upholds the highest standards on drug safety and other countries consider the FDA as the "lead agency" for drug approvals and drug safety. How is it possible that the FDA and Health Canada can have access to the same data and draw such completely different conclusions? Part of the answer lies in the fact that Canadian legislation allows suspension of a drug while security concerns are investigated, whereas in the US this course of action is not permissible. This difference may not be obvious to the casual observer who could not help but wonder if the FDA is being over-protective of their own position trying to avoid another scandal that another drug withdrawal would bring. Several US newspapers reported that U.S. Senator Charles E. Grassley alleges that the FDA asked Canadian regulators not to pull the drug because the agency couldn't handle another crisis over drug safety. Grassley indicated his information came from FDA whistle-blowers and the FDA declined comment on the accusation.
The official line from the FDA is that they will continue to evaluate post-marketing reports of serious adverse events in all individuals being treated with Adderall and related products.
“When one considers the rate of sudden death in pediatric patients treated with Adderall products based on the approximately 30 million prescriptions written between 1999 and 2003 (the period of time in which these deaths occurred), it does not appear that the number of deaths reported is greater than the number of sudden deaths that would be expected to occur in this population without treatment.”
This stance from the FDA will undoubtedly help Shire Pharmaceuticals Group Plc in their quest to get Canadian regulators to reverse their decision to suspend the sale of Adderall®.
The Canadian ADHD/ADD Resource Alliance (CADDRA) has also weighed-in to put pressure on Health Canada to overturn their judgment saying that the sudden announcement has resulted in panic among patients and families who are abruptly stopping their medication.
“Precipitous discontinuation of a medication without adequate consultation with physicians created a serious public health emergency that was unnecessary and far exceeded the potential risk of sudden death that Health Canada was reviewing.”
It’s not just Adderall
However, it is not just Adderall® that is causing concern. The FDA has logged seven sudden deaths of children taking Ritalin® and Concerta® during the period 1999 and 2003, and while these may not be statistically significant to FDA scientists the figure must surely raise concern for parents administering these drugs to their children.
Just this week, more disturbing news has been circulated concerning Ritalin®. Researchers at the University of Texas M.D. Anderson Cancer Center in Houston and the University of Texas Medical Branch at Galveston (UTMB) have just released some alarming results on Ritalin®. In a small study on just 12 children taking Ritalin® they found that every child experienced a significant increase in their level of chromosome abnormalities - occurrences associated with increased risks of cancer and other adverse health effects.
While potentially shocking, much larger studies are obviously needed to confirm the preliminary findings.
Brain Viagra
Whereas it may become more difficult to obtain Adderall® legally in Canada, there are multiple reports that this and other drugs prescribed for ADHD are finding their way onto college campuses and, in some cases, into high schools in Canada, the United States and Europe.
Adderall® is reportedly being used by students who believe it helps their ability to concentrate while studying or doing homework by increasing their ability to focus. Others are taking it to lose weight based on its appetite-suppressant qualities and others believe that the drug enables them to stay sober longer and stay up longer. It has been described as “like doing cocaine but it's cheaper". An article published in the student newspaper for the University of Rhode Island, stated that “Students on campus said that Adderall can cost anywhere from $2 to $10 a pill depending on the dosage.”
Other ADHD drugs such as Ritalin® are also illegally changing hands, trading under names such as “Vitamin-R” and “Brain Viagra”.
In the United States, Ritalin® and Adderall®, are controlled substances, and therefore illegal use of is punishable under the Federal Controlled Substances Act. Similar controls are in place worldwide to prevent the illegal sale of these drugs.
Bad science
Rather than treating attention deficiency, perhaps we should be teaching attention. Just think of the average child’s day - the hectic classroom environment, the frenzied pace of children’s television shows, and the salt, sugar and additive content of the average diet. Add to this the pressure to participate and succeed in extra-curricular activities – is it really any wonder children have difficulty paying attention?
Hopefully the actions of Health Canada will provide a much needed wake-up call to everyone involved in children’s healthcare. The medical profession must develop objective diagnostic criteria for ADHD. There are currently no objective diagnostic criteria for ADHD and the diagnosis of ADHD should not and can not be determined by a positive response to medication. Parents and children have a right to be fully informed of both sides of the ADHD debate so that meaningful informed consents can be obtained before any child receives stimulant drugs. Parents, educators, the medical profession and the pharmaceutical industry all need to take a long, hard look at the diagnosis of ADHD and possible treatment options. It is simply bad science to attempt to treat something before we know what it is.