How should drugs properly be studied for use in children? Only two of the newer psychotropic drugs have been approved by the FDA for the treatment of a psychiatric condition in children. Paxil and Luvox, both variations of Prozac, have proved effective in clinical trials required by the FDA for the treatment of pediatric obsessive compulsive disorder (OCD). No other medication, as yet, has met FDA approval. Several drug trials in children, actively supported by the pharmaceutical industry, are under way.

Once a drug is approved for use by the FDA for the treatment of a specific medical condition, a doctor can legally prescribed it "off label" for any purpose. Virtually every other med used to treat children's behavior is prescribed this way. Off-label use of medicines in pediatrics is common, but nowhere more so than in psychiatric medications. Physicians are constrained only by their own judgment and ethics. Local hospital and medical boards usually do little to interfere with doctors' preferences for treatment.

Most of the drugs used to treat children's emotional problems first became available after they met the FDA's standards for approval in psychiatric clinical trials in adults. A few were initially approved for use in adults for other medical conditions: Depakote and Neurontin for control of seizures, clonidine for blood pressure.

The typical path to the widespread use of any of these drugs for children begins with a report of a single child's response to a drug, usually as a letter in one of the professional journals. Journal editors explicitly state their openness to these kinds of "case" reports and more critical peer review scrutiny is omitted. The report will generate other letters until a series of cases are reported in which everyone -- the kids, parents and doctors -- knows what drug the child is taking.

Such studies are notorious for creating expectations of both positive and unwanted placebo effects. In the only study demonstrating the effectiveness of Prozac in children when the patients and doctors didn't know which pill was taken, 60 percent of the improvement in depressive symptoms was attributed to the placebo effect.

The Super Bowl of drug testing, which supposedly can distinguish between the actual effects of the active ingredients of a medication and placebo, is called the double-blind randomized control study (DBRCS). In a DBRCS neither the family nor doctor knows whether the child is getting the medication or an identical capsule filled with an inert ingredient. Only the pharmacist who prepares the medication knows which capsule contains the drug to be tested.

Patients are carefully screened for the psychiatric condition to be treated and then are randomly selected to receive either the real drug or the placebo. The children are monitored by their parents and doctors for improvements and side effects; along with benefits coming from placebo, many children complain of unwanted effects like headache and stomachache while taking placebos. After a pre-determined period it is revealed who took the drug and who took the the placebo. Only then does one learn the "real" vs. "believed" effects of the drug.

Such DBRCS are expensive; until recently, pediatric psychopharmacology researchers have been limited by low funds for their studies. Those few DBRCSs that had been run usually included only enough children, usually fewer than 100, to generate the likelihood of a statistically significant difference between drug and placebo required for scientific journal publication, but not enough for FDA approval.

But with only scores of children assessed, drugs like Prozac, imipramine, clonidine and Wellbutrin have come to be prescribed for hundreds of thousands of children. Research with imipramine demonstrated that adult drug studies do not necessarily correspond to effects in children. Nonetheless, adult medication trials are regularly invoked to justify the use of those same agents in children.

Calls for increased funding for pediatric psychopharmacology research are ubiquitous within the child mental-health community. The pharmaceutical industry, which now sees a children's market large enough to justify the expense, is funding several large studies, hoping to obtain FDA approval for the tested drugs.

On the other hand, studies on psychosocial interventions provide no similar profit-driven initiative for investigation. The much lower funding for this kind of research comes primarily from government. However, with the profit-motive incentive to develop new drugs and the real-life pressures to medicate children these days, there is ever-increasing pressure to medicate.

When all you've got is a hammer, everything starts to look like a nail.

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