My youngest son is a charming conversationalist. He
is not shy. Without prompting and to the surprise of
his mother, he offers a small, outstretched hand when
introduced to adults, along with a polite, ‘Nice
to meet you, Mr. X.’ He is popular among his peers,
who inevitably greet him with an explosion of his name.
He is also sensitive and emotional. He has difficulty
switching from one activity to another. And he worries.
He worries when the gas gauge gets low on the minivan.
Birthday parties make him so uneasy that he more often
than not won’t attend. Just before he turned 7,
he was brooding about death and the possibility that
our graves might not be side by side.
Last winter, the worries started taking over his better
half. Suddenly, in the middle of first grade, he refused
to ride the bus to school. He cried every morning, and
in order to part company with me, he had to be led away
gently but firmly to perform some special job by a member
of the school staff. Then the crying spells extended
to recess, the hallways, and he began to dread going
back to school at the start of the weekend.
Things came to a head just before Memorial Day. Seth
was more upset than usual on the drive to school because,
he fretted, he would be sent to the principal’s
office if he cried. I assured him that was ridiculous.
But his tearfulness had become so disruptive to his
class, it turned out to be true. Although I had had
telephone and sidewalk consultations with the school
guidance counselor, that morning I found myself face
to face with her. She was worried that his classmates,
now curious and concerned, would be less forgiving next
year. Mrs. Miller, I think it’s time to get
outside help for your son.
Such a statement can jolt even the most experienced
and enlightened parent. You may believe rationally that
anxiety and depression are bona fide illnesses, but
in your heart you are looking for a cause and, probably,
taking stock of yourself. Then, once you’ve accepted
that your first-grader needs a therapist, you have to
actually find one—one who’s good at an imperfect
and “artful” science; one who practices
near your home, is taking new patients and has appointments
that fit into your life; and one who is compatible with
your insurance company.
For me and Seth, a miracle occurred. The very next
day, a co-worker forwarded an e-mail from Hopkins’
child psychiatry division about a clinical trial recruiting
children with anxiety. I called immediately and passed
the first eligibility test. The following week, Seth
underwent an eight-hour assessment over two days that
measured everything from his I.Q. and blood pressure
to his fear of insects. To make sure the readings weren’t
off, he was reassessed using a shorter version a week
later. The results showed that Seth had ample “generalized
anxiety disorder” to qualify for one of four arms
of the study: medication only, cognitive behavioral
therapy only, a combination of the two, or placebo.
As it happened, he was randomized to the “pill
only” group, which meant he’d receive either
Zoloft, a drug that has successfully alleviated anxiety
symptoms in children, or a sugar pill (placebo) containing
no medication at all. And because this was a double-blind
study, neither his doctors nor his parents would know
which he was taking.
Incredibly, three-fourths of prescription medications
used to treat children have never been tested in children.
As a result, most of the drugs approved by the Food
and Drug Administration have labels that read, “Safety
and effectiveness in pediatric patients have not been
established.” Even ibuprofen bottles, until recently,
were labeled “Ask your doctor” for dosing
information for children under age 2.
For doctors who treat young children, this shortage
of hard evidence about how their patients will respond
to medications turns prescribing into a guessing game.
Pediatricians solve the problem by using data from adults
and adjusting the dose downward according to the weight
of the child. It’s a practice that has occasionally
gone awry: In the 1950s, many newborns died of “gray
baby syndrome” because their immature livers couldn’t
break down the antibiotic chloramphenicol that had been
used widely in adults.
Still, despite such potentially devastating consequences,
the public has remained reluctant to “experiment”
with medications on children. If children couldn’t
legally volunteer for research, the thinking went, they
shouldn’t be used as subjects in research.
Slowly, however, as it became recognized that children
are not small adults, the pediatric community called
for changes to the system. In 1977, the American Academy
of Pediatrics was the first to declare that it was more
unethical for children to be exposed to drugs of unknown
safety than to be enrolled into carefully controlled
clinical trials. The true experiments, in other words,
were taking place every time a child was prescribed
an untested medicine.
Last to come around to this point of view have been
the drug companies who fund so many of today’s
costly clinical studies of medications. “The pharmaceutical
industry has never really wanted to do trials in kids,”
says Hopkins child psychiatrist John Walkup. “It’s
a delicate patient population. And since doctors prescribe
[drugs] off-label anyway, why should they? Why should
they risk being held liable if something goes wrong?”
Nowhere has this threat been more real than in the
emotionally charged area of psychotherapeutic drugs.
“A lot of the people who complain about giving
medicine to these kids would rather teach them meditation,
or pray about it. It’s not attention deficit hyperactivity
disorder (ADHD), it’s ‘Boys will be boys.’
It’s not depression, it’s the divorce rate.
It’s an issue that spans science, medicine, religion
and politics, in a way that medicines for migraines
and hypertension don’t.
“We realize that we are part of a maelstrom,”
Walkup says. “We know that what we do is controversial
and why. But we also realize that science is the only
Seth was among the first volunteers in the Child/Adolescent
Anxiety Multimodal Study (cams) sponsored by the National
Institute of Mental Health. Eventually, the trial will
enroll some 318 youngsters over a period of three years.
Based at seven academic medical centers across the nation,
it will attempt to pinpoint the best way of treating
kids with anxiety. Studies, including those completed
at Hopkins by Walkup and Mark Riddle, director of child
and adolescent psychiatry, have shown that both medicine
and behavioral therapy are effective. This study would
treat some children with only medication, some with
only cognitive behavioral therapy and some with a combination
of the two approaches. And, as in any well-constructed
clinical trial, one group of children would receive
simply a pill containing sugar (a placebo), since the
efficacy of an approach can only be demonstrated by
comparing it to no treatment at all.
Mark Riddle: “Compared
to what we know in other disciplines,
our knowledge [in child psychiatry]
is way too limited.”
Seth was excited to be in the study and never once
put up his usual fuss about the excursions away from
our suburban cul-de-sac into the city. He enjoyed the
little treats he was allowed, like experiencing the
magic of inserting dollar bills into the soda and snack
machines, and the attention lavished upon him by the
staff. Our routine was to come in for weekly “med
checks,” during which both of us would fill out
a questionnaire customized to Seth’s particular
fears. The psychiatrist would meet with us briefly to
see how things were going, would sometimes adjust the
dose, and then we’d get our new “prescription”
at the investigational pharmacy. With the exception
of some trepidation about doing the hula in front of
his summer camp friends, Seth had relatively few setbacks
during June, July and August, but I was holding my breath
waiting for the start of second grade.
Child psychiatry was born at Johns Hopkins. Its founding
father, Leo Kanner, a medical graduate of the University
of Berlin, was brought to Hopkins by Adolf Meyer in
1928. Eight years later, Kanner offered the first formal
elective course in the subject here. But it wasn’t
until the 1960s that the first NIH grant to study pediatric
psychopharmacology was awarded. It went to one of Kanner’s
students, Leon Eisenberg, the second director of the
Still, as late as 1983, when Mark Riddle finished his
training in child psychiatry, the field was still considered
“a boutique, very specialized, non-mainstream
specialty.” Since then, some effective medications
and therapies have come along for children, “but
compared to what we know in other disciplines,”
Riddle says, “like cardiology, oncology, orthopedics,
our knowledge is still way too limited. Psychiatric
disorders are common in kids and they can be disabling.
If a child has anxiety and is socially inhibited for
a long time, the disorder can affect development. You
get into this work,” Riddle says, “and you
realize, My gosh! There’s a lot of work to be
done. There are a lot of kids and families out there
Much of the controversy over prescribing psychotherapeutic
drugs to children has stemmed from the nature of studies
that have already taken place. One of the most urgent
questions today has to do with whether giving antidepressants
to children, particularly the class known as selective
serotonin reuptake inhibitors (SSRIs), causes them to
have suicidal thoughts. Last year, British health authorities
banned the use of all the SSRIs except Prozac in kids
under 18, citing evidence from unpublished studies suggesting
an unacceptable risk of suicidal behavior in children
and teenagers. The FDA quickly followed suit with its
own probe, cautioning doctors against prescribing the
Early in February, the agency held an advisory committee
meeting to examine the risks and benefits of the drugs.
Dozens of researchers, doctors and relatives of children
who used the antidepressants testified. On one side
of the aisle, bereaved parents, clutching photos of
loved ones, blamed their children’s suicides on
the very drugs meant to help them. Others credited the
medications with saving their children’s lives
and were booed by the crowd. A month later, the agency
urged drugmakers to put new warning labels on the drugs.
Even Prozac, the only approved drug for children, has
barely crossed the threshold of efficacy in some trials
because too many kids taking placebos seemed to improve.
“If you had a cancer treatment that you were testing
against placebo and 70 percent got better with a placebo,”
Walkup says, “you’d say, it’s probably
not cancer. Depression is a very serious illness that’s
associated with massive impairment, long-term dysfunction,
risk for bipolar disorder, risk for suicide. You have
a big, hunkin’ disorder like major depression
and you say that 70 percent got better from placebo?
That disorder is not what was in that trial.”
Still, Walkup cautions against quick reactions. “Negative
studies can be negative for a million reasons. There
may be too many sites with too few patients and investigators
who are not well trained. It may be because the outcome
instruments have been conceptualized poorly. But that
doesn’t necessarily mean the drug is bad.”
Child psychiatrists, however, worry that muddy data
of this sort could erode the public’s confidence
in them even further. With only about 7,500 to 8,000
practitioners to serve a population of more than 15
million children and adolescents with diagnosable psychiatric
disorders, already the profession is battling a critical
workforce shortage. And the cases keep piling up. Not
only are the disorders being increasingly stripped of
their stigma but the population under 18 is expected
to grow by more than 40 percent in the next 50 years.
“The goal for the Hopkins group is to have enough
research dollars to answer the questions people want
answered,” Riddle says.
The first big, coordinated investment by the federal
government to study psychiatric problems in youngsters
began just 10 years ago, when the National Institute
of Mental Health (NIMH) funded a multisite, four-arm
clinical trial of Ritalin in children with attention
deficit hyperactivity disorder (ADHD). Now, Hopkins
is taking part in a second controversial study of the
same disorder that will attempt to pinpoint the most
effective treatment. This time, preschoolers with ADHD
will receive intensive behavior management followed
by medication. The results, not yet published, will
be scrutinized within the profession.
“We’re not just trying to push drugs,”
Riddle assures—his own research interests include
the metabolic side effects of medications. “It’s
risk and benefit, always. ADHD is a chronic problem,
so these kids need to be kept on medicine for a while.
Will they have growth problems as a result?
“The government has limited funds and wants more
complicated studies, the kinds of studies we’re
involved in—comparing psychotherapy to medicine,
figuring out how to treat non-responders, figuring out
how to treat kids with combination medicines. There
are just a few of us here who have the credentials to
do this stuff, and for years we’ve patched things
together in order to get the leverage to do the next
thing. Now we’re doing the studies we want to
Over the next few months, child psychiatry at Johns
Hopkins plans to launch another important clinical trial.
Enrolled this time, will be a small group of children
who have attempted suicide. “And this is a very
difficult issue to study with a safe, straightforward,
uncomplicated method,” Walkup says. “You
can’t try to help children who’ve tried
to take their own lives with a drug only vs. placebo
study. [As a parent] would you sign up for that?”
Instead the trial will treat some patients with medication,
others with sophisticated psychotherapy, and the remainder
with a combination of the two treatments.
Both Riddle and Walkup make clear that child psychiatry
carries more than medications and talk therapy in its
black bag these days. It’s just as important to
give parents the support and skills they need.
“Parents can have trouble with kids who don’t
have any problems,” Walkup explains. “They
kind of wing it, they collect advice, they read books,
they worry, they talk to their friends and neighbors
and patch it together, and by the time they’re
done with their kids, they’ve kind of figured
out how to do it. But with kids with emotional problems,
the mistakes you make along the way may add to the burden
of the illness and the kids may accumulate additional
disability. Most of the time, parents come in wondering
if a medicine will be helpful. I say, Well it might
be, but let me teach you about the disorder and empower
you to manage it. And for most families, it’s
that second part that they’re really interested
Nevertheless, both Walkup and Riddle are heavily invested
in clinical research in children with emotional problems.
“What we need to serve kids best is solid information
gathered in a very careful, thoughtful way about what
works and what doesn’t,” Riddle says, “what’s
harmful and what isn’t. People worry about kids
being guinea pigs, and there should be concern about
that, but if we just focus on that issue, research would
come to a halt. It’s our obligation to make sure
that kids aren’t harmed, and I think the mechanisms
are in place to ensure safe and high-quality work.”
At the end of Seth’s 12-week clinical trial,
he had improved. He happily started school, then regressed
to his crying jags but was righted fairly quickly. We
were offered six months of follow-up treatment, but
I couldn’t bear the burden of the appointments
any longer. I couldn’t imagine how any parent,
particularly a working parent, could manage the back
and forthing. By the time we dropped out, the research
team had recruited 16 kids, and all but one (too anxious
to take the medication) had made it through the 12 weeks.
How, I wondered, would they ever recruit 53?
Seth, now a second-grader, at the
Seth seems better. In February, on a day when school
opened late due to snow and he was sent to a neighbor’s,
he boarded the bus as if it had never been a problem.
And now, reader, you will want to know which arm of
the study Seth was in. Did he receive medication or
a placebo for his anxiety disorder? I regret to inform
you that I am not at liberty to say. At least until
the paper comes out in 2006.