May 02, 2007 03:00 AM

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EvanKitchens, a cheerful fourth-grader who loves basketball and idolizeshis 16-year-old brother, had been hospitalized for mental illness bythe time he was 8.

The boy from Bandera,Texas, was aggressive and hyperactive and had been diagnosed with avariety of other ailments, including obsessive-compulsive disorder andan autism spectrum disorder.

A couple ofyears ago, Evan was taking five psychiatric drugs, says his mother,Mary Kitchens. Two were so-called atypical antipsychotics, a group ofrelatively new drugs approved by the Food and Drug Administration fortreating adults with schizophrenia or bipolar disorder.

“Evanwas a walking zombie on all those drugs,” Kitchens says. At theharrowing nadir two years ago, she wondered whether her son wouldsurvive, let alone live a normal life.

Evanshook with severe body tremors and hardly talked. He had crossed eyes,a dangerously low white blood cell count and a thyroid disorder, allsymptoms that emerged after he started the atypical antipsychoticdrugs, Kitchens says. Now, he has been weaned from the drugs and takesmedicine only for attention-deficit disorder, she says. And he ismentally healthier than he has ever been.

Thesesix new antipsychotic drugs — Clozaril, Risperdal, Zyprexa, Seroquel,Abilify and Geodon — are not approved for children, but doctors canprescribe them to kids “off label.” And prescribing atypicalanti-psychotics for aggressive children such as Evan is leading thefield in a growing pediatric business, according to a new analysis of afederal survey by Vanderbilt Medical School researchers.

Outpatientprescriptions for children ages 2 to 18 jumped about fivefold — fromjust under half a million to about 2.5 million — from 1995 to 2002, thesurvey shows.

At the same time, reports ofdeaths and dangerous side effects potentially linked to the drugs areincreasing. A USA TODAY analysis of Food and Drug Administration datashows at least 45 deaths of children from 2000 to 2004 where anatypical was considered the “primary suspect.” More than 1,300 casesreported bad side effects, including some that can be life threatening,such as convulsions and a low white blood cell count.

Non-drug treatments

Treating children’s disruptive behavior with pills is a complicated issue and the subject of debate among experts.

“Inmy experience, and that of many psychiatrists, antipsychotics are oftenoverused for aggression in young patients,” says Ronald Pies, aclinical professor at Tufts University and author of Handbook of Essential Psychopharmacology.

That doesn’t mean it’s necessarily wrong to give the pills, he adds.

Nobodydisputes that the lives of schizophrenic or severely manic childrenmight be saved by antipsychotics. But many non-drug treatments can helpto keep aggressive, disruptive children off the atypicals, says JohnMarch, chief of child and adolescent psychiatry at Duke UniversitySchool of Medicine.

So much hinges on whether safer treatments can work for a child.

Kidswho show up on antipsychotics for aggression often can be weaned off ifthere are family changes, says behavioral pediatrician Lawrence Dillerof Walnut Creek, Calif. For instance, adolescents may lash out angrilyif their parents are fighting or discipline is inconsistent, Dillersays. In a divorce, the child sometimes ends up with the less effectiveparent.

Last year, Diller saw an 8-year-oldboy on four psychiatric drugs, including an atypical. He lived with hismother, “a highly anxious, incompetent parent.” When he went to livewith his father, his symptoms virtually disappeared, and he didn’t needany drugs, Diller says.

Child psychiatristGeorge Stewart says he has seen dozens of aggressive children weanedoff the atypical antipsychotic drugs in his consulting work and asmedical director of a residential treatment facility in Concord, Calif.Too often, he says, doctors give the drugs without considering familyconditions or life experiences that cause aggressive behavior, whichcan be changed with intensive counseling. Three examples he offers:

•A boy younger than 3 was treated with two antipsychotics at atherapeutic preschool for kids with severe behavior problems. Stewartgot a full family history, discovering his teen mother had a series ofabusive boyfriends. “He was acting out due to that, but nobody took thetime to find out what was going on at home,” says Stewart, who workedwith the mom to improve conditions. “She settled down.”

The child was taken off atypicals and is doing fine.

•A 12-year-old boy with out-of-control rage — “we’re talking smearingpoop all over the ‘quiet room’ ” — was treated at Stewart’s center.Intensive therapy identified the sources of his rage and taught the boyhow to cope. He returned home, off all meds.

•A teen girl seemed to be intractably violent. “She was trying to stabpencils in people’s eyes,” Stewart says. It turned out she had beenraped and experienced other severe trauma. She was weaned offantipsychotics and counseled. Now in her late teens, she’s livingindependently and doing well with no psychiatric drugs.

Oneof the most disturbing, potentially dangerous trends linked toatypicals is called “polypharmacy”: routinely giving kids severalpsychiatric drugs, says child psychiatrist Joseph Penn of BradleyHospital and Brown University School of Medicine in Providence. “Weknow very little about the interaction of these drugs, the effects theycould be having on kids,” he says.

Thebenefits of prescribing multiple drugs may outweigh risks in somecases, but Penn says he is appalled at how many times he has seen themega-powerful atypicals prescribed to children suffering from insomniawhen they’re taking other medicines.

“I’veseen hundreds of cases,” he says, “and often parents don’t seem to havebeen told about the many less risky prescription and non-prescriptionoptions out there.”

Sometimes medicalconditions or drugs for attention-deficit hyperactivity disorder causethe insomnia. Rather than attacking causes, doctors add an atypical tothe mix, he says.

More research needed

Therehas been little carefully controlled, long-term research on childrentaking most psychiatric drugs, including the atypical antipsychotics.The FDA is trying to get more pediatric research on the atypicals, saysThomas Laughren, the agency’s director of the psychiatry productsdivision.

The FDA has asked fivepharmaceutical companies that make the drugs to test them in childrenwith schizophrenia and bipolar disorder, the uses they’re approved forin adults. Under law, they can get a six-month extension on theirpatents for doing these studies.

Also, thedrug companies are doing their own pediatric studies on children withdisorders as diverse as ADHD, autism, conduct disorder and Tourette’ssyndrome.

Janssen LP has applied to the FDAfor approval to use its atypical antipsychotic, Risperdal, in thetreatment of symptoms of autism, says Ramy Mahmoud, vice president ofmedical affairs for Janssen.

The NationalInstitute of Mental Health also is conducting pediatric studies, butthe research is primarily funded and supervised by pharmaceuticalcompanies.

Even if the companies winapproval, it won’t guarantee safety or effectiveness of the drugs inchildren, says David Graham of the FDA Office of Drug Safety, whoemphasizes he doesn’t speak for the agency. “You basically know thedrug isn’t cyanide. You don’t know much else,” says Graham, who was thewhistle-blower in the 2004 Vioxx heart disease scandal. Industry-fundedtrials are four to five times more likely than independent studies toshow effectiveness for a drug, he says.

Accordingto a research review published in February, 90% of drug-company-fundedstudies come up with findings that support the company’s drug.

Inhead-to-head research testing more than one atypical antipsychoticdrug, the outcomes are contradictory, coming down on the side ofwhichever company is paying for the research. (The research includedstudies of Risperdal, Zyprexa, Clozaril and Geodon, but none onSeroquel or Abilify.)

“It appears thatwhichever company sponsors the trial produces the better antipsychoticdrug,” writes lead author Stephan Heres of the Technical University ofMunich in the American Journal of Psychiatry.

And the short-term, smaller studies required of companies rarely detect any but the most glaring problems, Graham says.

“TheAmerican public is operating under the illusion that a drug is safejust because it’s approved by the FDA,” says Jeffrey Lieberman,chairman of psychiatry at the Columbia College of Physicians andSurgeons in New York. Studies lasting a few weeks to a few months, witha couple of thousand patients total, won’t reveal all that’s wrong witha drug, he says.

Laughren agrees that “it’svery difficult to answer every question we’d like to answer with thesestudies, because obviously they’re not huge. Sometimes bad things thathappen are going to be discovered only when a drug is used more widely.”

Hesays he, too, shares concern about the antipsychotics prescribed forchildren without proof of safety or effectiveness. Much more pediatricinformation on the atypicals will be available within five years, hesays.

Recommended changes

Othersfavor fundamental changes to get the needed facts about drug safety.Lieberman thinks one solution would be for the FDA to be given a newlegal authority: the right to require drug companies seeking to gainapproval of a drug to contribute to a collective pool at the NationalInstitutes of Health. The NIH could supervise larger safety andeffectiveness studies of medicines after they’re on the market.

Anational electronic medical records database that would capture all badside effects of drugs, and require ages and diagnoses, could do a lotto protect children from careless prescribing and reveal the effects ofantipsychotics, Duke’s March says.

“We know so little about what’s happening to all the kids who are getting these powerful antipsychotics,” he says.

Marchalso thinks more private insurers ought to insist that aggressivechildren with short fuses try non-drug therapies proven to help beforedoctors jump in with antipsychotics. These pills can seem like anappealing “quick fix,” he says, so they’re popular.

Forfoster children with mental health problems, medication is a mainstay,says Ira Burnim, legal director at the Bazelon Center for Mental HealthLaw, an advocacy group for those with mental disabilities. There’sproof that the most effective care is “wraparound,” he says, meaningthat caseworkers touch base regularly with a child’s school, doctor,foster and perhaps birth families, in addition to ensuring therapy ormedication as needed.

“Now they’re medicatingmany kids instead of giving them the services they need. But there’svery little time spent with psychiatrists and not much attention paidto side effects from these heavy drugs,” Burnim says.

Statesvary in how much wraparound care they provide for foster kids, “but atypical pattern is patches here and there,” Burnim says. “They relyheavily on medications like the antipsychotics. This costs more thanwraparound in the long run, and it’s less safe for the kids.”

Marchconsiders the widespread use of antipsychotics on children withoutproof of safety or effectiveness “a very large experiment.” Many kidsare getting the short end of the stick, he says. “We’re not evengathering good data on the outcome of the experiment. It’s the worst ofall possible worlds.”