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?
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By Lawrence H. Diller, M.D.
May 23, 2002 | 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.
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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?"
