Chemical kids

Throughout the 1990s, family physicians and psychiatrists in the US would compare notes in clinic hallways and at conferences: The scuttlebutt was about a perceived boom in prescriptions for drugs designed to treat a range of mental conditions - for kids.

Recently, researchers have been putting hard numbers to the trend, confirming a dramatic rise - as much as a threefold increase - in the share of young patients treated with stimulants, antidepressants, "mood stabilizing" anticonvulsants, and other psychotropic drugs that previously had been prescribed primarily for adults.

The rise has been so steep and so sudden that the medical community is itself

debating with new vigor whether such drugs are being overprescribed. For some researchers, the new studies raise other fundamental questions such as whether young people taking drugs such as Ritalin and Prozac are being properly diagnosed and whether the dosages - and even the medications themselves - are appropriate.

Increasingly, doctors see conditions such as attention deficit hyperactivity disorder (ADHD) as "lifetime disorders," says Julie Zito, an associate professor of pharmacy at the University of Maryland at Baltimore. "If that means that you can start a child on a stimulant at the age of three and tell him he's going to take it for the rest of his life, we are into a very new world."

One key difficulty, researchers say, is that healthcare professionals prescribing these medications have at their disposal little data on how the compounds may affect the still-growing mind and body of a young person in the long term. It's a tough debate, with physicians on the front lines trying to balance their desire to help a youngster and family in distress by prescribing such drugs with their uncertainty about the risk to the child in the long term.

"A lot of kids we see are in terrible shape and can use whatever tools we have to help them get their lives back together again. Sometimes pharmacological tools are quite helpful," says James Leckman, a professor of child psychiatry and pediatrics at Yale University in New Haven, Conn. But "there's a lot we don't know about how these medications work, and it may be that we're putting a few children at risk for problems down the road."

In January, Dr. Zito and colleagues from two other institutions published what many say is the most comprehensive study yet of trends in psychotropic drug treatment for people under the age of 20. From 1987 to 1996, the proportion of young patients treated with psychotropic drugs in three large healthcare programs doubled, and in some cases, more than tripled. The study covered nine classes of medication and nearly 900,000 young people.

"This increase in use is really dramatic," Zito says, especially over such a relatively short period.

Another study, published last spring, looked at the prevalence of psychotropic treatments for groups of more than 500,000 young people who were in employer-insured healthcare programs. It found that the number of young people being treated with any of four classes of psychotropic medication rose from 38 per 1,000 in 1995 to 52 per 1,000 by 1999.

Zito says her own study prompts two questions: "Why have these numbers increased so rapidly and dramatically, and how appropriate is this increase in use?"

Explanations for the increase are numerous - and mostly conjectural.

Some researchers cite an explosion of research during the 1980s and 1990s on how the brain functions. Those findings led the medical community to tend to attribute kids' behavior problems more often to physiological causes. For instance, a child who seems unable to stay in his seat during class is now more likely to be treated for a chemical imbalance in his brain rather than trained to change his behavior. This new emphasis on neurological diagnoses has been followed automatically by a growth in pharmaceutical treatments.

Changes in the nation's healthcare system may also have played a role. During this same time, skyrocketing healthcare costs became a burning national issue, and in an effort to bring costs down, many managed-care plans outsourced their psychiatric services to specialized for-profit clinics, says Michael Jellinek, chief of child- psychiatry services at Massachusetts General Hospital in Boston. In an editorial accompanying Zito's January research paper, he explains that the for-profit clinics found that they could cut costs and earn tidy returns by using medication instead of counseling and other forms of "talking therapy." By prescribing medication, doctors can see more patients in an hour than they do otherwise. In short, the economic incentives favor medication.

Factored into these developments is pressure from patients or parents themselves, who may say they have seen a particular drug improve the behavior of a friend's or neighbor's child and so want to try it in their own case, says Oakley Ray, a psychiatry professor at Vanderbilt University and executive secretary of the American College of Neuropsychopharmacology. In the absence of strong evidence of significant risk, the patient's expectations that a drug will help - and a willingness to go elsewhere if the family pediatrician fails to prescribe something - are strong incentives for a physician to write the prescription, he says.

Giving properly dosed "potent anti- psychotic drugs" to a two-year-old diagnosed with schizophrenia, rather than waiting to medicate until the child is older, "solves the problem for the patient, for the parents, for society, and for the physician," Dr. Ray says.

Many physicians defend the use of such drugs for youngsters, noting the compounds have been on the market for years and clinical experience shows they are helpful. Moreover, the medicines have been reformulated as research narrowed the range of chemicals or nerve elements in the brain that the drugs target.

Still, little research exists on the drugs' long-term effects on youths, particularly young children. Many physicians, though, prescribe these medications for children "off label" - ignoring the recommended restriction for age and dose levels on the packaging and using their clinical experience to cut the dose to a level they feel would be effective for youths.

In 1997, the US Food and Drug Administration began encouraging drug companies to conduct studies to establish appropriate dose levels for young people on a range of drugs, including some psychotropics. Last June, for example, Ritalin was approved for use and the dosage set for children ages 6 to 12.

"Things have gotten a little better" over the past few years, says Yale's Dr. Leckman. "We have some knowledge of what the short-term effects are, how effective the drug might be, and the range of side effects."

But the practice of giving off-label prescriptions continues, researchers say, and has worked its way down to preschool-age children.

Concerns about misdiagnosis are also mounting among child-health professionals. In the current issue of the journal Pediatrics, for example, researchers at the University of Louisville reported that certain sleep disorders can lead to hyperactivity in young people, which might be misdiagnosed as ADHD. The researchers found that once the sleep problem was handled, about one-quarter of the children (ages 5 to 7) identified as ADHD kids were able to give up ADHD medication.

Given the uncertainty over long-term effects of psychotropic drugs on young people, researchers are trying to fill the data gap. Even as the studies answer some questions, they add new ones.

Paradoxically, one of the key treatments for young people diagnosed with ADHD is amphetamine-like stimulants. This has raised concerns that exposure to stimulants at an early age could lead to drug-addiction problems later in life. A research team at McLean Hospital in Belmont, Mass., in an experiment with rats, found the opposite. Rats exposed at a young age to methylphenidate, a stimulant often prescribed to young ADHD patients, later in life did not find cocaine to be pleasurable and, in some cases, had an adverse physical reaction to it.

That alleviates one worry, but the research may imply that something basic is happening to the brain, says William Carlezon Jr., director of the behavioral genetics lab at McLean Hospital and one of the researchers. He explains that methylphenidate may increase the amount of a chemical that, early in a person's physical development, guides the growth of the brain's neurons and encourages them to make the proper connections.

Treatments based on methylphenidate "may fundamentally change the connections that occur," leading to a "rewiring of the brain," Dr. Carlezon suggests.

A key question, he adds, is whether this rewiring is occurring and, if so, whether it has the potential to suppress the brain's reward-and-pleasure system and cause depression later. Those experiments are under way.

Clinicians, meanwhile, face a need to help their patients. For many, the issue is not a drugs/no drugs debate, but one of appropriate use given all the tools at hand, the diagnosis guidelines that exist, and experience with available medications.

"I'm always delighted and impressed" when the medications work, says Leckman. But he nonetheless is prescribing drugs less frequently than he used to and is putting more emphasis on counseling and other person-to-person therapies.

"For a lot of these kids," he says, "real success in life is going to depend on their interests and on how we can build on their strengths."