We're conducting a very large experiment on our children: New anti-psychotic dru

[Guest guest]

SSRI-Research@

Tue, 2 May 2006 18:16:53 -0400

[sSRI-Research] We're conducting a very large experiment on

our children: New anti-psychotic drugs carry risks for children

 

 

 

 

 

New anti-psychotic drugs carry risks for children

By Marilyn Elias, USA TODAYTue May 2, 7:21 AM ET

 

http://news./s/usatoday/20060502/ts_usatoday/newantipsychoticdrugscarry\

risksforchildren

 

Nancy Thomas remembers the bad old days when she had to wear

long-sleeve clothes to church to cover bite marks all over her arms

from her daughter Alexa's rages.

 

 

At age 8, Alexa was diagnosed with bipolar disorder. She was a violent

child with sharp mood swings and meltdowns that drove her to tear up

the house. Antidepressants and drugs for attention-deficit disorder

had only made Alexa more aggressive, Thomas says.

 

 

A mix of medicines including so-called atypical anti-psychotics -

drugs approved only for adults - finally stabilized Alexa's moods. Now

at 15, she is able to live a more normal life - as long as she takes

the medication.

 

 

Even so, the Russellville, Mo., teen is paying a price: On one of the

atypical anti-psychotics, Alexa gained about 100 pounds in a year,

putting her at risk for a host of health problems, including diabetes.

It has taken her three years to lose a third of that extra weight; she

is still struggling with the rest.

 

 

Atypicals are a new generation of anti-psychotic drugs approved by the

Food and Drug Administration for adult schizophrenia and bipolar

disorder (manic depression). None of the six drugs - Clozaril,

Risperdal, Zyprexa, Seroquel, Abilify and Geodon - is approved for

kids, but doctors can prescribe them as " off-label " medications.

 

 

Psychiatrists say the drugs can be helpful for children with serious

mental illnesses and have been known to save young lives [and

destroy... how many????]. But diagnosis often is difficult, making

appropriate prescribing tricky. And many experts, including behavioral

pediatrician Lawrence Diller, author of Should I Medicate My Child?,

say there is growing overuse of these powerful anti-psychotics.

 

 

Schizophrenia is rare in children under 18: It strikes about 1 in

40,000, as opposed to 1 in 100 adults, according to the National

Institute of Mental Health. Nobody knows exactly how many kids have

bipolar disorder; psychiatrists don't even agree on criteria to

diagnose the disease in childhood.

 

 

Research on how the drugs affect children is sparse, and experts

increasingly are concerned that the drugs are being prescribed too

often for children with behavior problems, such as attention-deficit

disorder and aggression.

 

 

John March, chief of child and adolescent psychiatry at Duke

University School of Medicine, prescribes the drugs to kids in some

cases of serious illness when he thinks the benefits outweigh the

risks. But he says prescribing them for behavior problems alone may be

a mistake. " We have no evidence about the safety of these agents or

their effectiveness in controlling aggression, " he says. " Why are we

doing this? "

 

 

At the same time, reports of deaths and dangerous side effects linked

to the drugs are mounting. A USA TODAY study of FDA data collected

from 2000 to 2004 shows at least 45 deaths of children in which an

atypical anti-psychotic was listed in the FDA database as the " primary

suspect. " There also were 1,328 reports of bad side effects, some of

them life-threatening.

 

 

Drug companies are required to file any reports they have to the FDA,

but consumers and doctors report such events on a voluntary basis.

Studies suggest the FDA's Adverse Events Reporting System database

captures only 1% to 10% of drug-induced side effects and deaths,

" maybe even less than 1%, " says clinical pharmacologist Alastair J.J.

Wood, an associate dean at Vanderbilt Medical School in Nashville. So

the real number of cases is almost certainly much higher.

 

 

" We're conducting a very large experiment on our children, " March says.

 

 

Side effects that linger

 

 

Some parents tell stories of serious effects that linger long after

their kids stop taking the drugs.

 

 

Rex Evans' parents are bitter about what happened to their son. They

believe the 13-year-old Colorado Springs boy was harmed permanently by

an atypical anti-psychotic he took several years ago. Rex now has a

serious case of tardive dyskinesia (TD), suffering daily episodes of

involuntary jerking movements and facial grimacing, says Erin Evans,

his mother.

 

 

Anti-psychotics are known to cause TD, but it's thought to be a rare

effect for the newer atypicals.

 

 

Despite such reports, outpatient prescriptions for kids ages 2 to 18

leaped fivefold - from just under half a million to about 2.5 million

- from 1995 to 2002, according to a new analysis of a federal survey

by Vanderbilt Medical School researchers. This doesn't include

prescriptions at psychiatric hospitals or residential treatment centers.

 

 

And even though the drugs are approved only for adults, the rate of

children treated with atypicals " is growing dramatically faster than

the rate for adults, " says Robert Epstein, chief medical officer for

Medco Health Solutions, pharmacy benefit managers.

 

Medco did an analysis of outpatient prescriptions for USA TODAY and

found that, in a sampling of about 2.5 million of Medco's 55 million

members, the rate of children 19 and under with at least one atypical

prescription jumped 80% from 2001 to 2005 - from 3.6 per 1,000 to 6.5

per 1,000. And that only represents kids who are privately insured,

not those in foster care or others on Medicaid.

 

" We know these are very strong medicines, " Epstein says. " You'd want

to be absolutely sure the child needs it. "

 

The more serious risks

 

Because of the nature of the FDA data, they don't prove that these

drugs caused the deaths or the side effects. Many side effects for

which an atypical is listed as the " primary suspect " occurred in the

normal course of using the drug, but the database also includes cases

involving drug abuse, overdoses, suicides and homicides. Entries are

sometimes cryptic, and the FDA enters verbatim - misspellings and all

- what's reported on the form.

 

Still, the data " can be a useful signaling device " suggesting problems

with a drug that warrant conclusive studies, says Jerome Avorn, a

pharmacology specialist at Harvard Medical School and author of the

book Powerful Medicines.

 

One-fourth of the cases in the database studied by USA TODAY did not

list the patient's age. But in cases that listed an age under 18:

 

.. A condition called dystonia was most often cited as an " adverse

event " suffered by someone taking one of the drugs, with 103 reports.

Dystonia produces involuntary, often painful muscle contractions.

 

.. Tremors, weight gain and sedation often were cited, along with

neurological effects such as TD. Symptoms of TD can vary from slight

twitching to full-blown jerking of the body.

 

.. A condition called neuroleptic malignant syndrome, with 41 pediatric

cases over the five years, was the most troubling effect listed, says

child psychiatrist Joseph Penn of Bradley Hospital and Brown

University School of Medicine. It is life-threatening and can kill

within 24 hours of diagnosis. It's been linked to drugs that act on

the brain's dopamine receptors, which would include the atypicals,

Penn says.

 

The FDA office of drug safety checks the database, " and we haven't

been alerted to any particular or unusual concern, " says Thomas

Laughren, director of the agency's division of psychiatry products.

" The effects (in kids) are similar to what we're seeing in adults. We

have not systematically looked at the data for children " because the

drugs aren't approved for them, he says.

 

The 45 deaths

 

Among the 45 pediatric deaths in which atypicals were the primary

suspect, at least six were related to diabetes - atypicals carry

warnings that the drugs may increase the risk of high blood sugar and

diabetes. Other causes of death ranged from heart and pulmonary

problems to suicide, choking and liver failure.

 

An 8-year-old boy had cardiac arrest. A 15-year-old boy died of an

overdose. A 13-year-old girl experienced diabetic ketoacidosis, a

deficiency of insulin.

 

More than half of the kids who died were on at least one other

psychiatric drug besides the atypical anti-psychotic, and many were

taking drugs for other ailments.

 

The youngest, a 4-year-old boy whose symptoms suggested diabetes

complications, was taking 10 other drugs.

 

The reports don't tell the child's general state of health or other

factors that could predispose him to trouble. Also, neither Clozaril,

which is rarely used, nor Abilify, the newest atypical, was listed as

a primary suspect in any deaths.

 

All the drugmakers emphasize that their products are not approved for

children, and they say the drugs are safe and effective for adults

with schizophrenia or bipolar disorder who are monitored for side

effects. Still, " there are worrisome questions here, " says Avorn.

Large, longer-term database studies could provide answers, he says.

 

There's some evidence that the drugs can help young schizophrenics and

may be helpful in treating bipolar disorder in children, says Robert

Findling, a child psychiatrist at University Hospitals of Cleveland.

 

But the data from controlled studies " are too few to guide treatment

decisions " on bipolar disorder, concluded Findling's research team in

a summary of pediatric studies published in the Journal of Clinical

Psychiatry.

 

These anti-psychotics are the most widely used class of drugs to treat

disruptive kids who attack others and defy adults, Findling says.

Again, there's a paucity of proof that the drugs help.

 

There are only a handful of carefully controlled, sizable studies

testing the drugs for any pediatric disorder, and they're mostly

short-term, says Benedetto Vitiello, chief of child and adolescent

psychiatry at the national mental health institute. The most serious,

widespread problem found to be caused by the medicines is weight gain,

he says. The effect varies by drug, but kids typically put on twice

the pounds they should in their first six months on atypicals.

 

In the first three months on the drugs, children add about 2 to 3

inches to their waistlines, says research psychiatrist Christoph

Correll of Zucker Hillside Hospital in Glen Oaks, N.Y. A lot of this

is abdominal fat, which increases the risk of diabetes and heart

disease. Obese children are twice as likely as normal-weight children

to have diabetes, according to a new University of Michigan study.

 

" Some patients gain weight on Zyprexa and others do not, " says Calvin

Sumner, a medical adviser to Eli Lilly Research Laboratories. Lilly

makes the drug, which has been associated with weight gains in adult

studies. Sumner stresses that Zyprexa isn't approved for kids.

 

There's no proof atypicals cause diabetes, says Ramy Mahmoud of

Janssen LP, maker of Risperdal. He says the FDA added a label warning

of increased diabetes risk " to make people aware of the possibility. "

 

One key question about atypicals is whether they will have long-term,

unknown effects on the brains of children.

 

The brain system that the drugs work on develops through childhood and

adolescence, says Cynthia Kuhn, a Duke University pharmacologist. " We

really don't know the impact of chronically perturbing that system in

childhood. "

 

Why atypicals get prescribed

 

Given all the potential problems, why would doctors prescribe these

drugs to children to begin with?

 

Nobody disputes that the lives of schizophrenic or severely manic

children may be saved by anti-psychotics. " I use them myself for

patients, " says March, the Duke psychiatrist. " I have a 9-year-old who

threatened to jump out of a second-story window if her mom didn't give

her the car keys to drive down to the 7-Eleven to get a Coke. If I

took her off anti-psychotics, she'd disintegrate. "

 

But several factors can lead to misprescribing of anti-psychotics.

 

It can be difficult to tell one behavioral disorder or illness from

another in kids. For example, the aggression and irritability of

bipolar disorder can mimic attention-deficit hyperactivity disorder or

depression, the mental health institute says. Also, the environment

can be a key cause of symptoms that may be mistakenly diagnosed as

mental disorders, says Diller, the behavioral pediatrician. Some

events in a child's life can trigger acting-out or other symptoms.

Adults can explain what happened to them; children, especially the

youngest, may be more reticent.

 

Doctors often face time pressures that prevent them from finding out

what's going on in kids' lives, knowledge that might suggest

alternative treatments, Penn says. For example, abuse of drugs such as

methamphetamine, OxyContin and cocaine is fairly common among teens,

he says. Kids begin acting strangely, hearing voices, becoming

paranoid. The symptoms can mimic psychosis or behavioral disorders,

and doctors can end up giving these children unneeded anti-psychotic

drugs, he says.

 

Insurance coverage rules may encourage the soaring use of

anti-psychotics for children, as well. " With some companies, the only

thing they reimburse for is prescribing. There's little or no

therapy, " says Ronald Brown, editor of the Journal of Pediatric

Psychology and a dean at Temple University.

 

Also, kids with serious mental health problems often have at least one

hospitalization, but policies cover only a week or two.

 

It can take a couple of weeks just to get medical records and family

histories, Penn says, but insurers often extend time if there's a new

medicine started, which encourages drug dabbling for children who are

not ready to go home.

 

In the end, some parents say their children have such severe behavior

disorders or mental illness that the benefits outweigh risks.

 

Parents of children such as Alexa Thomas, who have bipolar disorder,

say the atypicals often help. " We were very fortunate, " says Alexa's

mother, special-education director for the Russellville, Mo., school

district. " The medication worked for my daughter. It doesn't work for

everybody. "

 

Misdiagnosis common

 

The Vanderbilt study of anti-psychotic prescribing finds at least 13%

of pediatric prescriptions are for bipolar disorder. But there is some

concern about over-diagnosis and " jumping to this (bipolar) label too

quickly, " says psychiatrist Peter Jensen, head of the Center for the

Advancement of Children's Mental Health at Columbia University.

 

Sandra Spencer's son, Stephen, was diagnosed as bipolar at age 6 and

put on atypicals. He developed liver abnormalities and obesity, his

mother says. " He's been on a smorgasbord of meds, " she says. None

worked well for very long.

 

By the time he was in sixth grade, doctors said they weren't sure

Stephen was bipolar after all. Now 15, he is on low doses of an

antidepressant and mood stabilizer. He's being weaned off both, says

Spencer, executive director of the Federation of Families for

Children's Mental Health, a support group.

 

She worries about how the drugs have affected Stephen, who is black:

As little psychiatric drug research as there is on children, there's

least of all on minority kids. Some drugs are known to affect black

adults differently from whites. " He probably had ADHD all along, "

Spencer says. " Psychiatry is so not an exact science. "

 

Child psychiatrist Barbara Geller, a bipolar expert at Washington

University in St. Louis, agrees: " The science is nowhere near where it

is in other branches of medicine. "

 

So parents struggle to make the right decisions for very troubled

kids. " There's a lot of fear among parents, " Spencer says. " You don't

know what the effects of these drugs are going to be. You're at the

mercy of your doctor.

 

" I have had to make a lot of decisions, and they were fear-driven. You

don't have enough information to make an intelligent decision. "

 

 

2006 USA TODAY, a division of Gannett Co. Inc.