Children have become the new growth industry for
prescription drug makers. A study released last month by the pharmacy benefit
manager Medco found that 26% of kids under 19—almost
30% of those aged 10 to 19—are now taking prescription medications for a
chronic condition. Meanwhile, spending on prescription drugs for children
increased by almost 11% last year, the largest increase experienced by all
segments of the market, including the elderly. Although asthma drugs are the
still the most commonly prescribed therapeutics, kids are increasingly being
prescribed drugs that are decidedly uncommon for such young patients: atypical
anti-psychotics, diabetes drugs, anti-hypertensives, cholesterol medications
and heartburn drugs—expensive therapeutics that in the past were rarely used
outside of adult populations.

The Medco figures are alarming first of all because
intuitively it just feels wrong that so many children are downing prescription
pills along with their morning multivitamin and orange juice. Kids are supposed
to be healthy, full of energy, free spirited. But increasingly, this is not the
case. More than 17% of adolescents (10-19 year olds) are now classified as
obese: in fact, a whopping one out of three kids is considered overweight or
obese. And obesity brings with it a raft of formerly adult chronic
conditions.  According to a fact
sheet provided by the Institute of Medicine, in one population-based sample some 60% of obese children aged 5 to 10 years
had at least one cardiovascular disease risk factor—including high levels of
total cholesterol, triglycerides, insulin, or high blood pressure—and 25
percent had two or more of these risk factors.

According to the Medco report, the incidence of Type 2
diabetes increased over 150% in kids between 2001 and 2009. Meanwhile, the
industry newsletter The Pharmaletter reports that  “Type 2 diabetes medicines use by
juveniles increased 5.3% in 2009, the largest increase across all age groups,
and higher than overall utilization growth of 2.3%. Since 2001, the number of
children aged 19 and younger using these medications has risen more than 150%,
with girls between 10 and 19 showing the greatest jump at nearly 200%."

The news gets worse. A CVS Caremark study published in the
April 2009 issue of Archives of Pediatrics and Adolescent Medicine, found that
“over a two-and-a-half year period ending in June 2007, the use of medications
to treat high blood pressure, high cholesterol and diabetes among children
increased 15.2%.”  More evidence of
a problem: The number of children regularly taking proton pump
inhibitors, used to treat heartburn and GERD (also associated with obesity),
and in some cases prescribed for colic in infants, increased by 147% from 2001
to 2009.

The carefree view of childhood takes a bigger hit if you look at the Medco
findings on mental health. The study shows an increase in prescriptions for
ADHD drugs like Adderral and also highlights the trend for doctors to prescribe
so-called atypical anti-psychotics for their pediatric patients. The report’s
nine-year analysis revealed that the use of these treatments—which can have
serious side-effects that include weight gain and an increase in diabetes and
other metabolic problems—in children has doubled over that time period. While
atypicals are still more prevalent among boys, the rate of growth in girls aged
10-19 (130%) was the largest of all groups.

"Atypical antipsychotics are extremely powerful drugs that are being
used far too commonly – especially in children – given their safety issues and
side effects," commented David Muzina, a specialist in mood disorders and
national practice leader of the Medco Therapeutic Resource Center for
Neuroscience. "We're seeing them prescribed for a number of different
conditions including depression and anxiety for which there is not good
evidence that they are an effective treatment and yet we're exposing children
to the possibility of extreme weight gain that could lead to a host of health
problems including diabetes," Dr Muzina warned.

What’s also disturbing is that some 70-80% of drugs being
used to treat children have only been approved for use in adults. And in some
cases, especially when it comes to psychiatric drugs, they are also being used
for “off-label” indications: for example, a drug approved to treat
schizophrenia in adults is used to treat bipolar depression in children. The
net result is that without national registries or wide-range clinical trials
for many of these off-label drugs, children function as a giant, disorganized
experimental pool where trial and error, not evidence-based medicine, is the
rule of the day.

Children are not “small adults:” there are many questions
still to be answered about how drugs affect neurological development, growth
rates, metabolism and many other variables that are selectively affected at
differing stages of development. The FDA’s Office of Pediatric Therapeutics has
noted that increases in reports of central nervous system “events,” and other
unique physiological responses to medication in children suggest that
researchers may be considering the wrong endpoints when they are studying a
drug’s safety profile.

It’s interesting that just over a decade ago, most of the
controversy in pediatric therapeutics centered on the fact that due to a dearth
of clinical trials involving children, there were few suitable drugs for
treating pediatric problems. In response, in 1997 Congress authorized drug
companies to receive a six month extension of patent protection for certain
proprietary drugs if the companies conducted pediatric trials. These were drugs
that the FDA believed might be beneficial in treating childhood conditions that
had few therapeutic options.  In
2002 Congress went further and passed the Best Practices for Children Act 
that renewed the 6-month patent extension for drug companies, but also mandated
that an advisory group meet several times a year to review a wide range of  information received from doctors,
clinical investigators and advocacy groups about medications for children.

The
Act also requires that the advisory group (made up of representatives from the
FDA, NIH and outside pediatric experts) publish a list at least every 3 years
of drugs that should be considered as highest priority for government-funded
clinical trials. These are almost exclusively drugs that are older and no
longer have patent protection; and many are used to treat relatively rare
childhood conditions. Finally, the 2007 FDA Amendments Act reauthorizes for five years the agency’s authority to
require drugmakers to include assessments for pediatric use along with
applications for new drugs or new uses for drugs.

Since 1997, about 350 drugs have had their labels changed to include pediatric
indications—about 22% of the total number of drugs currently used to treat
children. Dr. Alan Stiles, Chairman of Pediatrics at University of North Carolina and a member of the FDA/NIH advisory group says
that the number of drugs that still need to be studied for use in children is
enormous. “It’ll probably take 1,000 years to do this because it’s so expensive
and it takes so long. Pharmaceutical companies have incentive to do this with
proprietary drugs because they can get a patent extension, but there is no
incentive for cheaper, generic drugs.” He gives the example of hydrochlorothiazide,
a 30-year-old drug that is commonly used to treat hypertension and metabolic
syndrome in adults. “This is not a drug that has had wide study in kids,” says
Stiles, “and it would never be studied by pharmaceutical companies. But it’s a
good, inexpensive, first-line treatment for kids.”

It makes far more sense to pharmaceutical companies to
intead finance pediatric trials for their new, more expensive drugs. A 2008
article in the American Heart Journal
looked at the economic results when companies took advantage of the FDA’s
6-month patent extension and performed pediatric studies on nine such
name-brand hypertension drugs. The conclusion: although companies spent an
average of  $5.2 million on safety
studies and pediatric trials for each hypertension drug, the authors concluded:
“the Pediatric Exclusivity Provision has generated highly variable, yet
lucrative returns to industry sponsors.”

The increase in prescription drugs marketed for pediatric
conditions will likely continue unabated. Obesity is a serious and growing
problem among young people, and the diagnosis of behavioral disorders—and the
accompanying pressure from schools, parents and practitioners to deal with them
through medication—also shows no sign of slowing. As rates of hypertension,
glycemic disorders, gastroesophageal reflux and asthma rise, so will the number
of prescriptions written for kids.

The FDA’s policies that encourage drug companies to conduct
pediatric clinical trials for their new proprietary drugs has brought mixed
results. It has increased the sheer number of therapeutics available for
treating difficult pediatric problems; but at the same time companies are also
now driven to recoup their financial investment. They increase marketing of
expensive, name-brand drugs—like the atypical antipsychotics—to doctors and even
consumers (who often have few other sources of information on appropriate
therapeutics for their young patients) and in some cases, drive inappropriate
medication of kids. Meanwhile, information on how these drugs affect
neurodevelopment, metabolism, growth rates and other long-term effects remains distressingly
elusive.

What we urgently need is a saner system for monitoring the
effects of a growing lexicon of prescription drugs used to treat our children.
Along with that is a need for a broader, more accessible and comprehensive
program for providing doctors with evidence-based recommendations for drug
therapy. This issue has been in the forefront recently with the growing use of
the newer atypical antipsychotic drugs in children and the need to monitor
their long term metabolic effects. A 2008 article in Child and Adolescent
Psychiatry and Mental Health details the need for stricter monitoring and reporting of all
effects—beneficial, adverse, long-term, etc.—in children taking psychiatric
drugs. Other groups have called for national registries to be set up so that
doctors and investigators can record pediatric clinical information—helping to
create a large database to help identify best treatments for various
psychiatric problems in kids. This same approach should be considered for
cardiovascular drugs and all others that have been used primarily in adults.

The Medco report provides evidence of a new reality. Due to
an epidemic of obesity, an increase in diagnosis of behavioral and mental
health problems and, in some cases, better drugs for controlling widespread
conditions like asthma, children are now an attractive—and growing—market for
drug companies. But first, caution. The dearth of knowledge concerning dosing,
contraindications, long-term effects and just plain suitability for children of
many drugs is striking. The solution is for the FDA and NIH to devote more
resources to conducting evidence-based studies, creating national registries
and putting together treatment guidelines for pediatric therapeutics. This particular
national resource is to precious to leave to chance.