A PRESCRIPTION FOR DISASTER

The failure to test the effects in children of routinely prescribed
drugs has resulted in at least one death. How many kids will die before
drug companies take steps to ensure their safety?

Ten-year-old Shaina Dunkle had been taking the psychiatric drug
desipramine (trade name, Norpramin) for her
attention-deficit/hyperactivity disorder (ADHD) last year, when she
suddenly fell and had a grand mal seizure. She died within minutes in
the arms of her mother, who watched helplessly as her daughter's life
ended. Shaina's autopsy revealed no other cause for her death than the
desipramine. Her parents, in the small central Pennsylvania town of
Smithtown, struggled privately with tremendous guilt and anger until
they began to learn more about their daughter's treatment. Now, the
outrage they feel about the circumstances of Shaina's death has
prompted them to go public with their concerns.

Shaina Dunkle should never have been on this drug. In the late 1980s,
child psychiatrists promoted desipramine for the treatment of ADHD. But
by the mid-1990s, reports of seven sudden deaths of children taking the
medication in appropriate doses for ADHD led most doctors to abandon
desipramine for other, "safer" medications. According to Shaina's
parents, desipramine was offered to them as a once-a-day drug that,
unlike Ritalin, the most commonly prescribed medication for ADHD, had
no abuse potential. However, when used properly Ritalin has not been
implicated in sudden death (the one reported exception was a
14-year-old boy who died suddenly after taking the drug for more than
10 years). The Dunkles were never told of the increased risk for this
catastrophic side effect related to desipramine.

Desipramine is just one of many drugs that received FDA approval for
treatment of an adult condition -- in this case depression -- but was
then, and apparently is still now, used in children for a variety of
behavioral and performance problems. Once the FDA approves a drug, it
can be used with a physician's prescription for any purpose, a practice
called off-label prescribing. Many doctors prescribe many medications
off label for children, but none do it as frequently as child
psychiatrists.

Child psychiatrists have long been viewed as the ultimate authorities
in the evaluation and treatment of children's emotional and behavioral
problems. Today, however, these doctors appear to be pushing pills
exclusive of anything else. In fact, a recent survey of child
psychiatry practices by the Yale Child Study Center, published in the
Journal of the American Academy of Child and Adolescent Psychiatry,
revealed that only one in 10 children who visit a child psychiatrist's
office leaves without a psychiatric drug prescription.

Even leaders within the community of child psychiatrists, doctors like
Michael Jellinek, the head of Harvard's child psychiatry department,
and Peter Jensen, former director of the head of the children's section
of the National Institute of Mental Health, have publicly expressed
concern that there is not enough evidence of the effectiveness and
safety of these medications to support their widespread use for kids.

And they should be concerned. About 4 million children take either
Ritalin, the only psychiatric drug adequately researched for use by
children, or an equally well-tested equivalent like Adderall, Concerta,
or Metadate. About 1.5 million children take adult antidepressants like
Prozac for a variety of problems. Hundreds of thousands are on various
other adult medications: clonidine, a drug originally approved for
adult hypertension, is prescribed to take the edge off difficult
behavior caused by ADHD, especially in the late afternoon or evening,
when taking a stimulant will keep the kid up all night. Depakote, a
drug tested in adults for epilepsy, is the latest prescriptive drug "in
fashion" for treatment of the burgeoning number of children diagnosed
with bipolar disorder. Risperdal, a "new generation" anti-psychotic
drug, is prescribed for children primarily to control aggressive
behavior.

None of these drugs, except Ritalin and others in its stimulant class,
have been tested in more than a few dozen children for more than about
two or three months. Even Ritalin, which has been around for decades,
has been studied no longer than 18 months for its effectiveness or
safety. Until recently, the pharmaceutical industry has had little
incentive to test drugs in kids -- the market wasn't large enough and
pediatric drug studies pose additional ethical hurdles.

But drug companies became very interested in drug trials involving
children about two years ago, when the government agreed to extend
exclusive patents on drugs for six months if the companies facilitated
testing in children. About two years after the extension, however, the
FDA, still not satisfied with the amount of pediatric testing being
done, introduced an administrative mandate that required drug companies
to test previously approved drugs frequently used in children. The move
brought three thinly veiled "citizen suits" funded by the drug industry
that challenged the FDA's authority. When the FDA backed down under
this pressure, child advocacy groups -- including the American Academy
of Pediatrics and the American Academy of Child and Adolescent
Psychiatrists -- expressed outrage. The FDA finally reinstituted the
mandate, with the apparent public approval of the Bush administration.

Now Sens. Hillary Clinton, (D-N.Y.), Christopher Dodd (D-Conn.), and
Mike DeWine (R-Ohio) are sponsoring legislation to make the testing
mandatory for drugs that are regularly prescribed for children.

But this proposal doesn't go far enough. At the moment, doctors and
their patients learn only in a haphazard fashion about the side effects
that develop with a drug's long-term use. There are no requirements for
what is called post-marketing surveillance -- for any drug -- despite
repeated calls for such a procedure from medical and patient advocacy
groups.

Drug companies aggressively oppose this kind of thorough follow-up on
drugs, not only because it is expensive, but because they don't really
want to find out whether their drugs continue to work over time or if
long-term side effects develop. Currently, that kind of research is a
job for the country's trial lawyers. But this de facto "system" of
monitoring the effects of drugs requires many casualties before an
adverse outcome is discovered or established in the medical and popular
literature.

At the heart of this debate is the recent surge in the use of
psychiatric drugs to treat children. So many children are taking these
medications that the need for more testing and follow-up is suddenly
crucial. Unfortunately, the alternative -- effective non-drug
interventions for the treatment of children's behavioral issues -- has
been overlooked.

Specific psychotherapeutic approaches to the treatment of behavioral
issues in children -- ADHD, anxiety and obsessive compulsive disorder
-- have been shown to eliminate or decrease the need for drugs. But the
pharmaceutical industry, with its control of psychiatric research
funding, influence in the media, and direct advertising to patients,
has no interest in the promotion of these approaches. The problem?
Psychosocial treatments like family therapy and special education do
not generate stock dividends or equity, and they are less available
than drugs.

If other interventions were more widely available and aggressively
promoted, it is possible that Shaina Dunkle's apparently mild ADHD
symptoms, diagnosed by her school psychologist, could have been managed
without medication. Yes, some children who do receive non-drug help can
still benefit from taking a psychiatric medication. But Shaina's
parents say they never would have given desipramine to their daughter
had they known more about it. They trusted the doctor; they believed
the drug to be safe.

The extensive prescription of these medications for children, without
adequate testing for safety and effectiveness in children constitutes a
hidden time bomb that could explode with still more casualties.
Catastrophic side effects, like the one that killed Shaina Dunkle, may
be rare, but they become predictable when we treat so many children
with so many drugs. We need to know more, much more. And until we do,
it is imperative that we give adequate consideration to treatments that
do not involve drugs whose full effects we don't completely understand.

About the writer: Lawrence Diller practices behavioral/developmental
pediatrics in Walnut Creek, California and is the author of "Running on
Ritalin" and the new book, "Should I Medicate My Child?"