Pill pressure

Contributed by The Financial Times health supplement - Published 17 December 2009

When Steven Rose, a neuroscientist, began observing the US debate on attention deficit hyperactive disorder in the 1980s, just a few thousand stimulants were being dispensed in the UK each year. Today, doctors in England alone write more than 700,000 prescriptions annually.“Diagnosis and prescriptions rocketed in the 1990s, and in the UK, the numbers just keep going up,” says Prof Rose, who teaches at the Open University. “It just seems to me to be the business of drugging children.”

His views reflect continued and intense debate over a condition that many have labelled an epidemic, as growing ADHD identification and medication spreads from the US around the globe, accompanied by the misuse of the amphetamines to enhance cognition in many more people.

US estimates suggest that about 5 per cent of the school age population has the symptoms: a combination of inattention, hyperactivity and restlessness. The proportion is significantly greater in some regions and groups, notably boys. In other countries, a growing number of studies suggests similar figures, while ADHD in adults is also garnering fresh attention.

Prof Rose’s concerns, like the condition itself, have a long history. Sir Alexander Crichton first wrote about “mental restlessness” in a book in 1798, and in 1902 the paediatrician Sir George Frederick Still lectured at the Royal College of Physicians on restless and fidgety children with a “quite abnormal incapacity for sustained attention”.

As Rick Mayes and colleagues from the University of Richmond described in a book published earlier this year on ADHD*, treatment with medicines – initially derived, as so often, largely through serendipity – began as early as 1937.

Doctors at the specialist Bradley Hospital in Rhode Island began using spinal taps on children as an experimental form of treatment for ADHD. When many complained of severe long-lasting headaches, they administered the amphetamine Benzedrine in an effort to raise blood pressure.

But they observed a calming effect, even in some children on the drug who had not received spinal taps, and began to wonder if it was the Benzedrine itself that was responsible for the improvements – in spite of the fact that the drug was better understood as a stimulant. Scientists believe today that in moderate doses, it seems to work partly by promoting inhibition.

In the decade after the second world war, Ciba-Geigy introduced the stimulant methylphenidate, branded as Ritalin, initially to treat psychosis. Clinical trials for children were launched with a haste that Mayes writes would be ethically questionable today, as teachers and parents enthusiastically committed their children to try out new treatments.

The results proved promising, and Ritalin was approved by regulators for use in “hyperkinetic behaviour syndrome” in 1961. Long a cheap, off-patent generic drug, it remains a mainstay of treatment today, and one that has been linked to relatively few side effects since.

In the 1970s, however, rising concern about the misuse of amphetamines triggered the introduction of strictly regulated annual supply quotas on the bulk materials released to medicine manufacturers. There was also a call for longer-lasting drugs that would remove the stigma and impracticality of children having to top up their treatments during the school day.

Adderall, containing a mix of amphetamine salts, was launched in the 1990s. First developed when its effects in hyperactive children were observed for what was originally a weight-loss drug, it was reformulated as Adderall XR (extended release) at the start of the decade, and the class has become the most widely used medication today.

In the US alone, the ADHD market is worth $4.5bn (£2.7m), covering an estimated 5.6m patients with 43m annual prescriptions. Such sales have spurred continued drug company investment, leading most recently to the launch of Vyvanse, designed to become pharmacologically active only in the bloodstream, reducing the risk of it being misused through smoking, injecting or crushing.

But are such sales justified? Mike Yasick, leader of the ADHD business unit at Shire, which sells Adderall and Vyvanse, argues there is no logic to his company overselling the drug. “Physicians are appropriately cautious,” he says. “We know these drugs are potent. It is not in our best interest to have kids with minor conduct problems on ADHD [medicines].”

Prof Rose is less convinced. “I am worried that these drugs are given to kids who are just a bit out of order,” he says. “It is primarily given to the child for the benefit of the teacher and parent. My concern is the coercive way it is being delivered, when a kid gets out of line and the parents are exhausted.”

His comments echo criticisms voiced since the 1970s by a disparate coalition of lawyers, journalists, parents and medical researchers, who have raised concerns about the medicalisation of the condition. They point to aggressive marketing by pharmaceutical companies, including directly to consumers in the US, and argue for broader psychological support, improved parenting and a greater tolerance for diversity in behaviours.

Mayes argues that other social factors also help explain the explosion of ADHD diagnosis and treatment in the US. Recognition has expanded in parallel with the growth in medical coverage to those on lower incomes through Medicaid, and greater provision of social security and educational support to those who have been diagnosed.

While most scientists point primarily to genetic explanations, there has also been discussion about the role and impact of artificial food colours and preservatives. The UK Food Standards Agency has encouraged manufacturers to voluntary withdraw the so-called “Southampton six” ingredients from their products by the end of this year, with requirements to disclose their presence elsewhere in the EU and the US.

But Eric Taylor from the Institute of Psychiatry in London says that while there may be some cases of “over-diagnosis” of ADHD, he observes the opposite in his clinic. “I see many more very distressed patients. I think there is much more under-treatment than disease-mongering.”

Certainly, several studies scanning research around the world since the turn of the decade have suggested that ADHD is not an “American disorder”, with similar rates of prevalence elsewhere. The main differences seem less related to culture than to the extent to which the condition is diagnosed, and how well the existing criteria are interpreted.

Philip Asherson from King’s College in London, a leading specialist in adult ADHD, says that while the condition can disappear as children age, an older generation was never diagnosed when younger, and some patients may only decide they need treatment once they reach adulthood.

One area in which critics and supporters of drug-based treatment can agree is the lack of data to understand the long-term effects of medication. Most clinical trials have taken place over weeks, with the longest lasting 14 months. Mike Yasick says Shire began a registry in 2008, that it will run over a minimum of four years to track the health of those taking its drugs.

Another point of discussion is that while the drugs do not appear to create addiction, they do not deal with the underlying causes, and symptoms resume if patients stop taking their medicines.

Prof Taylor cautions: “Patients may not have good self-esteem because they attribute all improvement to drugs. The stimulants deal with cognitive but not emotional instability.”

* Medicating Children: ADHD and Pediatric Mental Health, by Rick Mayes, Catherine Bagwell and Jennifer Erkulwater (Harvard University Press, 2009)

Read the PDF version of the article here.

For more articles from The Financial Times health supplement focused on health reform, click here.

From the Financial Times ©  The Financial Times Limited 2009. All Rights Reserved.
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