http://www.time.com/time/magazine/article/0,9171,1101031103-526331,00.html
Medicating Young Minds
Drugs have become increasingly popular for treating kids with mood and behavior
problems. But how will that affect them in the long run?
By JEFFREY KLUGER
Sunday, Oct. 26, 2003
Getting by is hard enough in middle school. it's harder still when you've got
other things on your mind—and Andrea Okeson, 13, had plenty to distract her.
There were the constant stomach pains to consider; there was the nervousness,
the distractibility, the overwhelming need to be alone. And, of course, there
was the business of repeatedly checking the locks on the doors. All these
things grew, inexplicably, to consume Andrea, until by the time she was through
with the eighth grade, she seemed pretty much through with everything else too.
"Andrea," said a teacher to her one day, "you look like death."
The problem, though neither Andrea nor her teacher knew it, was that her
adolescent brain was being tossed by the neurochemical storms of generalized
anxiety, obsessive-compulsive disorder (OCD) and
attention-deficit/hyperactivity disorder (ADHD)—a decidedly lousy trifecta.
If that was what eighth grade was, ninth was unimaginable.
But that was then. Andrea, now 18, is a freshman at the College of St.
Catherine in St. Paul, Minn., enjoying her friends and her studies and looking
forward to a career in fashion merchandising, all thanks to a bit of chemical
stabilizing provided by a pair of pills: Lexapro, an antidepressant, and
Adderall, a relatively new anti-ADHD drug. "I feel excited about things,"
Andrea says. "I feel like I got me back."
So a little medicine fixed what ailed a child. Good news all around, right?
Well, yes—and no. Lexapro is the perfect answer for anxiety all right,
provided you're willing to overlook the fact that it does its work by
artificially manipulating the very chemicals responsible for feeling and
thought. Adderall is the perfect answer for ADHD, provided you overlook the
fact that it's a stimulant like Dexedrine. Oh, yes, you also have to overlook
the fact that the Adderall has left Andrea with such side effects as weight
loss and sleeplessness, and both drugs are being poured into a young brain that
has years to go before it's finally fully formed. Still, says Andrea, "I'm just
glad there were things that could be done."
Those things—whether Lexapro or Ritalin or Prozac or something else—are
being done for more and more American children. In fact, they are being done
with such frequency that some people have justifiably begun to ask, Are we
raising Generation Rx?
Just a few years ago, psychologists couldn't say with certainty that kids were
even capable of suffering from depression the same way adults do. Now,
according to PhRMA, a pharmaceutical trade group, up to 10% of all American
kids may suffer from some mental illness. Perhaps twice that many have
exhibited some symptoms of depression.
Up to a million others may suffer from the alternately depressive and manic
mood swings of bipolar disorder (BPD), one more condition that was thought
until recently to be an affliction of adults alone. ADHD rates are exploding
too. According to a Mayo Clinic study, children between 5 and 19 have at least
a 7.5% chance of being found to have ADHD, which amounts to nearly 5 million
kids. Other children are receiving diagnoses and medication for
obsessive-compulsive disorder, social-anxiety disorder, post-traumatic stress
disorder (PTSD), pathological impulsiveness, sleeplessness, phobias and more.
Has the world—and American society in particular—simply become a more
destabilizing place in which to raise children? Probably so. But other factors
are at work, including sharp-eyed parents and doctors with a rising awareness
of childhood mental illness and what can be done for it. "While we don't know
exactly why the incidence of psychopathology is increasing in children and
adolescents, it probably has to do with better diagnosis and detection," says
Dr. Ronald Brown, professor of pediatrics at the Medical University of South
Carolina.
Also feeding the trend for more diagnoses is the arrival of whole new classes
of psychotropic drugs with fewer side effects and greater efficacy than earlier
medications, particularly the selective serotonin reuptake inhibitors (SSRIS),
or antidepressants. These have been rolled out with highly visible,
to-the-consumer ad campaigns. While an earlier generation of
antidepressants—tricyclics like Tofranil—didn't work in kids, SSRIS do.
According to a study by Professor Julie Zito of the University of Maryland
School of Pharmacy, use of antidepressants among children and teens increased
threefold between 1987 and 1996. And that use continues to climb. Nobody, not
even the drug companies, argues that pills alone are the ideal answer to mental
illness. Most experts believe that drugs are most effective when combined with
talk therapy or other counseling. Nonetheless, the American Academy of Child
and Adolescent Psychiatry now lists dozens of medications available for
troubled kids, from the comparatively familiar Ritalin (for ADHD) to Zoloft and
Celexa (for depression) to less familiar ones like Seroquel, Tegretol, Depakote
(for bipolar disorder), and more are coming along all the time. There are
stimulants, mood stabilizers, sleep medications, antidepressants,
anticonvulsants, antipsychotics, antianxieties and narrowcast drugs to deal
with impulsiveness and post-traumatic flashbacks. A few of the newest meds were
developed or approved specifically for kids. The majority have been okayed for
adults only, but are being used "off label" for younger and younger patients at
children's menu doses. The practice is common and perfectly legal but
potentially risky. "We know that kids are not just little adults," says Dr.
David Fassler, professor of psychiatry at the University of Vermont. "They
metabolize medications differently." Within the medical community—to say
nothing of the families of the troubled kids—concern is growing about just
what psychotropic drugs can do to still developing brains. Few people deny that
mind pills help—ask the untold numbers who have climbed out of depressive
pits or shaken off bipolar fits thanks to modern pharmacology. But few deny
either that we're a quick-fix culture, and if you give us a feel-good answer to
a complicated problem, we'll use it with little thought of long-term
consequences. "The problem," warns Dr. Glen Elliott, director of the Langley
Porter Psychiatric Institute's children's center at the University of
California, San Francisco, "is that our usage has outstripped our knowledge
base. Let's face it, we're experimenting on these kids without tracking the
results." THE CASE FOR MEDICATION
Those experiments, however, are often driven by dire need. When a child is
suffering or suicidal, is it fair not to turn to the prescription pad in
conjunction with therapy? Is it even safe? Untreated depression has a lifetime
suicide rate of 15%—with still more deaths caused by related behaviors like
self-medicating with alcohol and drugs. Kids with severe and untreated ADHD
have been linked, according to some studies, to higher rates of substance
abuse, dropping out of school and trouble with the law. Bipolar kids have a
tendency to injure and kill themselves and others with uncontrolled behavior
like brawling or reckless driving. They are
Which is why Teresa Hatten of Fort Wayne, Ind., hesitated little when it came
time to put her granddaughter Monica on medication. Hatten's grown daughter,
Monica's mom, suffers from bipolar disorder, and so does Monica, 13. To give
Monica a chance at a stable upbringing, Hatten took on the job of raising her,
and one of the first things she had to do was get the violent mood swings of
the bipolar disorder under control. It's been a long, tough slog. An initial
drug combination of Ritalin and Prozac, prescribed when Monica was 6, simply
collapsed her alternating depressed and manic moods into a single state with
sad and wild features. By the time she was 8, her behavior was so unhinged, her
school tried to expel her. Next Monica was switched to Zyprexa, an
antipsychotic, that led to serious weight gain. "At 12 years old she had
stretch marks," says Hatten. Now, a year later, Monica is taking a four-drug
cocktail that includes Tegretol, an anticonvulsant, and Abilify, an
antipsychotic. That, at last, seems to have solved the problem. "She's the best
I've ever seen her," says Hatten. "She's smiling. Her moods are consistent. I'm
cautiously optimistic." Monica agrees: "I'm in a better mood." Next up in the
family's wellness campaign: Monica's 8-year-old cousin Jamari, who is on
Zyprexa for a mood disorder. All along the disorder spectrum there are such
pharmacological success stories. In the October issue of the Archives of
General Psychiatry, Dr. Mark Olfson of the New York State Psychiatric Institute
reports that every time the use of antidepressants jumps 1%, suicide rates
among kids 10 to 19 decrease, although only slightly. But that doesn't include
the nonsuicidal depressed kids whose misery is eased thanks to the same pills.
ARE WE MEDDLING WITH NORMAL DEVELOPMENT?
For children with less severe problems—children who are somber but not
depressed, antsy but not clinically hyperactive, who rely on some repetitive
behaviors for comfort but are not patently obsessive compulsive—the pros and
cons of using drugs are far less obvious. "Unless there is careful assessment,
we might start medicating normal variations (in behavior)," says Stephen
Hinshaw, chairman of psychology at the University of California, Berkeley. The
world would be a far less interesting place if all the eccentric kids were
medicated toward some golden mean. Besides, there are just too many unanswered
questions about giving mind drugs to kids to feel comfortable with ever
broadening usage. What worries some doctors is that if you medicate a child's
developing brain, you may be burning the village to save it. What does any kind
of psychopharmacological meddling do, not just to brain chemistry but also to
the acquisition of emotional skills—when, for example, antianxiety drugs are
prescribed for a child who has not yet acquired the experience of managing
stress without the meds? And what about side effects, from weight gain to
jitteriness to flattened personality—all the things you don't want in the
social crucible of grade school and, worse, high school. Adding to the worries
is a growing body of knowledge showing just how incompletely formed a child's
brain truly is. "We now know from imaging studies that frontal lobes, which are
vital to executive functions like managing feelings and thought, don't fully
mature until age 30," says Hinshaw. That's a lot of time for drugs to muck
around with cerebral clay. For that reason, it may not always be worth pulling
the pharmacological rip cord, particularly when symptoms are relatively mild.
Child psychologists point out that often nonpharmaceutical treatments can
reduce or eliminate the need for drugs. Anxiety disorders such as phobias can
respond well to behavioral therapy—in which patients are gently exposed to
graduated levels of the very things they fear until the brain habituates to the
escalating risk. Depression too may respond to new, streamlined therapy
techniques, especially cognitive therapy—a treatment aimed at helping
patients reframe their view of the world so that setbacks and losses are put in
less catastrophic perspective. "The therapist teaches relaxation skills and
positive thinking," says Denise Chavira, clinical psychologist at the
University of California at San Diego. "It goes beyond talk therapy."
Unfortunately, medical insurance pays more readily for pills than these other
treatments for adults and children.
For kids with more serious symptoms, experts are worried that undermedicating
is a bigger risk than overmedicating. "Say you've got a kid who's severely
obsessive and literally can't leave the home because of the fears and rituals
he's got to perform," says ucsf's Elliott. "Think about what anyone age 2 to
age 16 has to learn to function in our society. Then think about losing two of
those years to a disorder. Which two would you choose to lose?" Also on the
side of intervention is the belief that treating more kids with mental illness
could reduce its incidence in adults.
Dr. Kiki Chang at Stanford University is trying to show that this is true with
bipolar kids. He recently published a study in the Journal of Clinical
Psychiatry that looked at kids from bipolar families who had only early signs
of the disease. Pre-emptive doses of Depakote eased early symptoms in 78% of
cases before the illness ever had a chance to take hold. "You can sit and watch
it develop or intervene and possibly prevent the disorder," says Chang. While
the researcher is excited about his results, he admits that treating kids who
are not yet truly sick is controversial. "There's a chance some of the kids
might not develop bipolar at all," says Chang. "We need to have more genetics,
more brain imaging, more biological markers to know which direction the kids
are going."
HOW CAN WE MEASURE THE RESULT?
Preventing symptoms, of course, is not everything. A sleeping child is
completely asymptomatic, for example, but that's not the same as being fully
functioning. If the drugs that extinguish symptoms also alter the still
developing brain, the cure may come at too high a price, at least for kids who
are only mildly symptomatic. To determine if this kind of damage is being done,
investigators have been turning more and more to brain scans such as magnetic
resonance imaging (MRI). The results they're getting have been intriguing.
MRIs had already shown that the brain volumes of kids with ADHD are 3% smaller
than those of unafflicted kids. That concerned researchers since nearly all
those scans had been taken of children already being medicated for the
disorder. Were the anatomical differences there to begin with, or were they
caused by the drugs? Attempting to answer that, Dr. F. Xavier Castellanos of
the New York University Child Studies Center took other scans, this time using
only kids with ADHD and comparing those who were taking medication with those
who were not. Reassuringly, he discovered that they all shared the same
structural anomaly, a finding that seems to exonerate the drugs.
Dr. Steven Pliszka, chief of child psychiatry at the University of Texas Health
Center in San Antonio, went further. He conducted scans that picked up not just
the structure but the activity of the brains of untreated ADHD children, and
compared these images with those from children who had been medicated for a
year or more. The treated group showed no signs of any deficits in brain
function as measured in blood flow. In fact, he says, "we saw hints of
improvement toward normal."
The news was less positive when it came to bipolar disorder. Chang has looked
at the brains of kids treated with Depakote, and while his study is as yet
unpublished, he says he noticed some anatomical differences that could result
from treatment—and he wasn't necessarily happy with them. "We are seeing that
medications do affect the brain acutely," he says. "Is that a good thing, a bad
thing? We just don't know."
What nobody denies is that more research is needed to resolve all these
questions—and that it won't be easy to get it started. The first problem is
one of time. It was only in the early 1990s that the antidepressant Prozac
exploded into pharmacies. It's hard to do a lifetime of longitudinal studies on
a drug that's been widely used for just over a decade. And each time the
industry invents a new medication, the clock rewinds to zero for that
particular pill.
Even if it were possible to conduct extended studies, getting volunteers for
the work is difficult. The attrition rate is high in any years-long research,
especially so when the subjects are kids, who bore easily and, at any rate,
eventually go away to college. On average, 40% of children will drop out of a
long-term study before the work is done. And that assumes their parents will
even sign them up in the first place. Some brain scans involve at least a
little bit of radiation—something most parents are reluctant to expose their
children to, particularly if those kids have no emotional disorders and are
simply being used as a baseline to establish the look of a healthy brain.
Getting good scans from kids who have diagnosable conditions isn't easy, as any
radiologist who has ever tried to conduct a lengthy MRI on a child with ADHD
can attest. "Holding still is not exactly what they do well," says Elliott.
Ethical questions hamstring research too. Any gold-standard study requires that
some of the kids who are suffering from a disorder receive no drugs so that
they can be compared with the kids who do. But if you believe the medications
are helpful, how can you withhold them from a group of symptomatic children who
need them? Despite such obstacles, research is moving ahead, if haltingly. The
National Institute of Mental Health is conducting a study called the Preschool
ADHD Treatment Study, in which researchers will track ADHD kids between 3 and 8
years old to determine the benefits and side effects of stimulant medications.
Castellanos and N.Y.U. colleague Rachel Klein are taking things further,
calling back subjects who were enrolled in an ADHD-treatment study that began
in 1970 to scan their now late-30s and early-40s brains for the long-term
effects of drugs. Castellanos is also planning a study of young rats treated
with varying amounts of psychotropic drugs, conducting dosing and anatomical
studies that cannot be performed on humans.
C O V E R
THE RISK OF HASTY PRESCRIPTIONS
Just as important as getting the research rolling is fixing the health-care
system kids rely on to get well. Like adults taking mind meds, children often
get their drugs not from a specialist in psychiatry and psychopharmacology but
from any M.D. with the power of the prescription pad. Usually this means the
pediatrician or family doctor, who isn't likely to have the time or training
necessary for the extensive evaluations needed before drugs can be properly
prescribed—much less the required follow-up visits. "There's no way you can
screen for side effects in a 10-year-old in five minutes," says Miami
neurologist Sara Dorison. "You have to chat about their summer, their friends."
Part of the reason for all the hurry-up drugging, say psychiatrists, is managed
care, which, already disinclined to pay for longer, more costly talk therapy,
is equally reluctant to foot the bill to make sure patients on pills are well
monitored. In a perfect—or at least better—world, says Elliott, parents
considering meds for their kids would have access not to one specialist but
three: a pediatrician, a behavioral pediatrician and a child-adolescent
psychiatrist. "Insurance companies talk about second opinions," he says, "but
they don't actually like them."
The pharmaceutical companies could be doing better too—and if they don't, the
government must push them to do it. There is a lot of money to be made in
developing the next Prozac, but there is less profit if you test it for longer
than the law demands. The Food and Drug Administration (FDA) doesn't require
long-term studies that follow patients over decades. Its only requirement is
toxicity trials that span six to eight weeks. In an effort to entice companies
to conduct lengthier studies, the agency now grants an extension of six months
of exclusive marketing rights to any company engaging in studies of a drug's
effects on a minimum of 100 children for more than six months. "It's a
relatively small amount of data," acknowledges Dr. Thomas Laughren, a
psychiatrist with the FDA's psychopharmacology division, "but it's better than
what we had before, which was nothing."
Until all these things happen, the heaviest lifting will, as always, be left to
the family. Perhaps the most powerful medicine a suffering child needs is the
educated instincts of a well-informed parent—one who has taken the time to
study up on all the pharmaceutical and nonpharmaceutical options and pick the
right ones. There will always be dangers associated with taking too many
drugs—and also dangers from taking too few. "Like every other choice you make
for your kids," says Chang, "you make right ones and wrong ones." When the
health of a child's mind is on the line, getting it wrong is something that no
parent wants.