Medicating Young Minds

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Getting by is hard enough in middle school. It's harder still when you've got other things on your mindand 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, Minnesota, 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, yesand no. Lexapro is the perfect answer for anxiety all right, provided that you're willing to overlook the fact that it does its work by artificially manipulating the very chemicals responsible for feelings and thought. Adderall is the perfect answer for ADHD, provided that you overlook the fact that it's a stimulant like Dexedrine. Oh, yes, you also have to overlook the fact that 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 thingswhether Lexapro or Ritalin or Prozac or something elseare being done for more and more children the world over. In the U.S., they are being done with such frequency that some Americans 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 be suffering from some mental illness. Perhaps twice that many have exhibited some symptoms of depression. Up to a million others may be suffering 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, American children between the ages of 5 and 19 have at least a 7.5% chance of being found to have ADHD, which amounts to nearly 5 million kids. In Japan, the Asian country most attuned to psychological problems in children, a survey of more than 40,000 elementary and middle school kidsthe first such large-scale study by the governmentrevealed that 2.5% were suffering from ADHD, which translates into one child in every schoolroom. Kwai Chung Hospital in Hong Kong, which runs one of the five main child psychiatric centers in the territory, has seen a doubling of ADHD cases since 1998 and an even bigger jump in kids diagnosed with schizophrenia. Other maladies affecting children: obsessive-compulsive disorder, social-anxiety disorder, post-traumatic stress disorder, pathological impulsiveness, sleeplessness, phobias and more.

Has the world simply become a more destabilizing place in which to raise children? Probably so. But other factors are at work, including sharper-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. While an earlier generation of antidepressantstricyclics such as Tofranildidn'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 BPD), and more are coming along all the time. There are stimulants, mood stabilizers, sleep medications, antidepressants, anticonvulsants, antipsychotics, antianxieties and 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 communityto say nothing of the families of the troubled kidsconcern is growing about just what psychotropic drugs can do to still developing brains. Few people deny that mind pills helpask the untold numbers who have climbed out of depressive pits or shaken off bipolar fits thanks to modern pharmacology. But in America, few deny that a quick-fix culture exists, and if you offer a feel-good answer to a complicated dilemma, people will 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 (UCSF), "is that our usage exceeds our knowledge base. We're learning what these drugs are to be used for, but let's face it: we're experimenting on these kids."




IS ASIA CATCHING UP?
Shohei Asakura was a restless and troubled child since he was several months old. He didn't respond normally to his peers, and his language development lagged behind other kids' in his neighborhood in Japan's Fukushima prefecture. At age 3, Shohei was diagnosed with ADHD and pervasive development disorder, but for a year his parents refused the doctor's offer of a "miracle drug," Ritalin. When they finally relented in 1999, Shohei's behavior changed almost overnight. He was more comfortable around his mother, Rei, and could concentrate for extended periods of time. But Rei is still apprehensive about her son's dependence on drugs and is sometimes criticized by people who respond to her website, which chronicles her son's struggle. "I could tell them only that I got him to take it because it was absolutely necessary," she says.

Asia is far behind the West in diagnosing kids with mental illness. "A gross number of children and teenagers who really need help are untreated," says Dr. Ahn Dong Hyun, president of the Korean Academy of Child and Adolescent Psychiatry. In all of India, for example, there are only a dozen child psychiatrists. In China, most parents have never even heard of conditions such as ADHD. "They tend to think their kids are misbehaving, disobedient, or that they don't like going to school," says Du Yasong, director of the department of child and adolescent behavior at the Shanghai Mental Health Center. "Their reaction is to blame the children, scold them, even beat them." And from that foundation of ignorance springs many more problems. Ritalin, for example, isn't approved in Japan for treating hyperactivity (although it is for severe depression and narcolepsy). The drug isn't officially sanctioned for any condition in China (although it is available to doctors there). Ritalin's manufacturer, Novartis Pharmaceuticals, doesn't even bother marketing the drug in Asia. But ADHD, the ailment for which Ritalin is most frequently prescribed, is at least starting to be diagnosed in Asian kidsfar more than depression, BPD or OCD. "The problem here," says Dr. Angeline Chan, a child psychiatrist in Hong Kong, "is undermedication."

Which suggests that Asian kids are impervious to the dangers of these drugsbut that's not true either. School performanceoften the first thing to be affected in a child with mental illnessis an obsession with middle-class Asian parents, and a whole lot of kids are hauled off to unqualified physicians who can dispense a pharmacopoeia of potentially dangerous drugs. Varkha Chulani, a Bombay-based child psychologist, saw a seven-year-old boy with ADHD last year who had suffered problems at school. His parents had brought him to a doctor who prescribed a slew of medications, including Valium and Alprax. "The child was on so many drugs, he had become a zombie," she says. In South Korea, school-obsessed teens self-medicate on powerful over-the-counter drugs, including amphetamines (to concentrate) and opiates (to counter anxiety and depression). "When we see these kids at the hospital," says Kim Hun-Soo, a psychiatrist at Seoul Asan Hospital, "it's because these drugs have changed their behavior so much that their previously nonchalant parents finally were able to notice a difference." Once the kids get off the street drugs, Kim says, some are found to have undiagnosed mental illness such as ADHD, depression and social-anxiety disorder, which should have been treated with entirely different drugs.

THE CASE FOR MEDICATION
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 such as 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 getting into trouble with the law. Bipolar kids have a tendency to injure or kill themselves and others with uncontrolled behavior such as brawling or reckless driving. They are also more prone to suicide.

Which is why Teresa Hatten of Fort Wayne, Indiana, hesitated little when it came time to put her granddaughter Monica on medication. Hatten's grown daughter, Monica's mom, suffers from BPD, 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 BPD under control. It's been a long, tough slog. An initial drug combination of Ritalin and Prozac, prescribed when Monica was six years old, simply collapsed her alternating depressed and manic moods into a single state with sad and wild features. By the time she was eight, her behavior was so unhinged that 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 eight-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 years old 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 problemschildren who are somber but not depressed, or antsy but not clinically hyperactive, or who rely on some repetitive behaviors for comfort but are not patently obsessive-compulsivethe pros and cons of using drugs are far less obvious. "Unless there is careful assessment, we might [inadvertently] 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 skillswhen, 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 personalityall 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 therapyin which patients are gently exposed to graduated levels of the very things they fear until the brain habituates to the escalating risk.

Depression, too, might respond to new, streamlined therapy techniques, especially cognitive therapya 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 for these other treatments for adults and children alike.

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 adulthood.




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 might 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 from 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 because 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 afflicted 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 BPD. Dr. Kiki Chang of Stanford University 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 have resulted from treatmentand 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 questionsand 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 new pill.

The pharmaceutical companies could be doing better in research, tooand if they don't, governments 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 U.S. 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 firm 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 parentone 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 drugsand 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.