Medicating Young Minds

By Jeffrey Kluger

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 also more prone to suicide.

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.

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. --With reporting by Dan Cray/Los Angeles, Alice Park/New York, Kathie Klarreich/Miami, and Leslie Whitaker/Jefferson City

With reporting by Dan Cray/Los Angeles, Alice Park/New York, Kathie Klarreich/Miami, and Leslie Whitaker/Jefferson City