Nudged by public pressure, Florida health officials took a baby step last year toward reining in the use of powerful antipsychotic drugs among children: They began requiring that doctors get approval before giving these drugs to kids under 6 on the Medicaid program.
That simple step prompted a seismic change in doctors' prescribing habits.
The number of prescriptions of these potent drugs to kids in this age group plummeted nearly 75 percent.
Another dramatic change: Nearly 40 percent fewer doctors are even bothering to write prescriptions for these drugs — including Risperdal, Abilify, Seroquel and Zyprexa — apparently finding alternatives that require less paperwork.
David Cohen, a Florida International University professor who has long questioned the rampant use of the new generation of antipsychotics among kids, applauded the steep decline. He wonders why anyone prescribes these drugs.
"Viewing the increase over the past 10 years, I couldn't imagine that many preschoolers needed the most powerful drugs available on the planet,'' he said. "I think the change is great, but is it enough?"
The state's review process has hardly been draconian, with approval going to nearly three out of four prescriptions submitted, mostly refills. But once Medicaid decided to take a closer look at the off-label prescribing of these drugs to preschoolers, about 200 physicians had this response: Never mind.
Since the preapproval process began, the state has denied one out of three prescription requests from Dr. Helene Hubbard, a Bradenton pediatrician who specializes in developmental problems.
"It's a terrible thing," said Hubbard, who was approved for 31 prescriptions in 2008 after writing 101 in 2007. "My kids are suffering."
Among them was 4-year-old Robert Bartlett, who had his Risperdal refill held up for a few weeks in December. Diagnosed as developmentally delayed, Robert had been taking the drug for about a year. Without medication, he started biting classmates and bouncing around the classroom during story time.
"The school called me several times, asking 'What's going on?' " said Cynthia Bartlett, whose 9-year-old also is on Risperdal. "When they're on the meds, they're still typical boys, but at least you can get them to pay attention. People get scared of antipsychotics, but believe me, on these drugs, they have a much better quality of life."
Florida instituted the requirement for prior approval in April 2008, after intensifying public debate over the proper use of this class of antipsychotics.
The new data compares the prescriptions of these drugs for kids younger than 6 from May to December 2008 to the same period a year earlier. The numbers do not include prescriptions for kids on Medicaid HMOs or private insurance because that data is not publicly available.
State figures show there was a 40 percent drop in the number of preschoolers receiving these drugs. Use was pared back at every age level and eliminated for infants under age 1, for whom there were 23 such prescriptions in 2007.
The number of kids under 6 prescribed more than one of the drugs also dropped, from 73 to 28.
The demand for drugs deemed essential just a year ago dried up; requests from doctors was cut by two-thirds.
Robert Constantine heads a group at the University of South Florida that monitors prescribing trends of antipsychotics for Medicaid. He said he plans to analyze what happened to the kids who were not given prescriptions.
"But there's been no major outcry from doctors," Constantine said. "And ordinarily we would have heard."
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Introduced in the 1990s for treatment of adult schizophrenia and bipolar disorder, the new class of drugs, called "atypicals,'' were touted as causing fewer side effects than first-generation, "typical" antipsychotics, such as Haldol. Despite their limited approved use, atypicals rapidly became best sellers, prescribed to adults for everything from mild dementia to insomnia.
Pediatric prescriptions skyrocketed as well, as doctors and parents alike became enamored of atypicals' ability to calm even the most fractious child. Though drug companies cannot promote unapproved or off-label uses, doctors can write such prescriptions. Atypical sales reps became frequent visitors to pediatricians' offices, often dropping off samples.
"Eighty percent of all the drugs a pediatrician uses are off-label because nobody tests drugs on kids," said Hubbard. "Unfortunately they don't let the companies sample atypicals to pediatricians anymore."
None of the atypicals have been approved by the FDA for use on preschoolers, and Florida Medicaid guidelines recommend they be used on this age group "only in the most extraordinary of circumstances." But those warnings didn't slow a tsunami of atypical prescribing. Between 2001 and 2004, the number of kids under 6 taking atypicals increased 300 percent. For all youths under 19, the increase was about 250 percent.
It wasn't until late 2006, well after the drugs were being widely prescribed to kids, that the FDA officially approved the use of Risperdal for irritability associated with autism for kids 5 and older.
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As the number of people taking atypicals rose, so too did reports of dangerous side effects. By late 2003, the FDA told atypical makers to add warnings of weight gain and diabetes. Lawsuits followed against all the drugmakers, alleging patient harm and illegal marketing.
The makers of Abilify and Zyprexa have settled off-label marketing claims, with Zyprexa's maker, Eli Lilly, paying a record $1.4 billion fine. Lilly also has paid $1.2 billion to settle patient lawsuits. Complaints against the makers of Seroquel and Risperdal have not been resolved.
The public's growing wariness about the drugs, particularly their pediatric use, was also heightened with disclosures of financial ties between the drugmakers and doctors.
Last year it was revealed that a leading proponent of the use of Risperdal in kids, Harvard's Dr. Joseph Biederman, received more than $1.6 million from the company that makes it, Johnson & Johnson. The company also funded a research center headed by Biederman with a goal "to move forward the commercial goals of J&J."
Sen. Charles Grassley, R-Iowa, has spearheaded a congressional investigation into doctors' financial ties to the drug industry. He has asked the American Academy of Pediatrics, American Psychiatric Association and American Medical Association to say how they're addressing concerns over pediatric use of atypicals.
Industry funding does not surprise or bother many child psychiatrists, including St. Petersburg's Dr. Mark Cavitt.
"In a perfect world, it would be much better if research were funded by independent agencies, but most of the research dollars in child psychiatry comes from the pharmaceutical companies,'' said Cavitt, who is with All Children's Hospital. "Now that drug companies are required to reveal negative as well as positive studies, I'm not overly concerned."
Cavitt has been involved in industry-funded atypical research and has spoken on behalf of Abilify. He has mixed feelings about the state's new preapproval process. "It's probably an important step in terms of establishing some regulation of medication that can be very helpful but have potential negative consequences and are expensive.''
Yet as a specialist who sees severely disturbed kids gouging their eyes and pummeling siblings, Cavitt appreciates the powerfully calming effects of atypicals.
"If they're monitored and dosed low enough that you can avoid side effects, an atypical can almost become a first-line instead of second- or third-line treatment,'' he said. "And you don't want to go through two or three failed trials to get to the best choice."
Since Medicaid's review process went into effect, Cavitt has had about five atypical prescriptions denied. He has reluctantly put those patients on first-generation antipsychotics.
"When I truly believe it's in the patient's best interest to be on an atypical and it gets denied, I'm frustrated," Cavitt said. "Overall the numbers are relatively low, but that doesn't console myself or the patient or his family."
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When a provider faxes Tallahassee a request to be allowed to prescribe an atypical for a preschooler, a Medicaid pharmacist reviews the one-page form and accompanying medical history and notes. If the prescription is for a refill, chances are good it will be approved.
If it's a new prescription, or if the child has been on the drug and stable for more than nine months, the paperwork hits the fax again. This time it ends up in a single-story, yellow-brick building at the University of South Florida in Tampa.
Two USF child psychiatrists, Drs. Michael Bengtson and Saundra Stock, take turns reviewing as many as 20 requests a week. Bengtson, who has experienced the hassles of prior approval himself, said they try to respond within 24 hours.
He understands doctors might want to use an atypical to sedate an uncontrollable child with ADHD, one of the most frequent diagnoses reported. But he rejects the request unless a recent evaluation shows the child is violently aggressive. Bengtson also wants proof the physician has first tried other medications with fewer side effects. And if the request is for an inappropriately high dosage, the answer is no.
On the other hand, kids who are autistic and aggressive are routinely approved for Risperdal, even if they're younger than the FDA age guidelines. "At least we have some safety data for autism," Bengtson said.
Of preschoolers who received prior authorization for atypicals in 2008, more than half were diagnosed with autism and PDD (pervasive developmental disorder). Risperdal was by far the atypical of choice, accounting for more than 70 percent of all prescriptions.
On Bengtson's desk one recent afternoon was a sheaf of papers documenting the troubles of a 5-year-old with ADHD, a family history of bipolar disorder and penchant for hitting teachers and scratching his face. Records showed the nurse practitioner had tried two conventional ADHD treatments. Notes from three office visits in the prior two months showed no improvement. Bengtson approved the prescription.
"This is not a cost-saving goal," he said of the prior approval process. "It's a question of whether these drugs are being used appropriately. And I think we've narrowed it down to a very small population."
Bengtson, who has one preschooler in his practice on atypicals, said he thinks most child psychiatrists were astounded when they learned how widely the drugs were being prescribed. He hopes the sharp decline in their use in Florida means children who didn't really need the drugs aren't getting them.
"But it may have made other challenges for the families," he said. "These are kids that have got just a bit more energy. I'm ashamed to say it, but atypicals work. But that doesn't make it the right thing to do."
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Bengtson said Medicaid doesn't want to continue the pre-approval process for atypicals indefinitely. At the same time, he can't explain why the review isn't required when the drugs are prescribed for older kids. "You may have the same concerns with an 8-year-old,'' he said.
Hubbard, the Bradenton pediatrician, cringes at the possibility. She already has a staffer whose job is to fax drug requests to the state and Medicaid HMOs after her Wednesday clinic in Arcadia, where she sees about 40 troubled kids.
She estimates that one-third to one-half of her patients under 6 are on small doses of atypicals, which she said stabilizes them so other interventions — sleep, nutrition, exercise, parental support — can take effect. Hubbard considers atypicals a temporary medication until the child learns to control his impulses, but she advises parents to keep a pill on hand for emergencies.
"Atypicals like Risperdal keep the kid from flying into a rage over a broken pencil tip," she said, adding that she has seen them tame even autistic toddlers doing a "naked dance."
"But I stress the medicine only lets the other interventions work. These drugs just calm them down so they can get back to school and their parents back to work."
Catherine Lambert-Power of North Port, who has three adopted sons in Hubbard's care, can attest to the power of Risperdal. All the boys have been diagnosed with fetal alcohol syndrome and intermittent explosive disorder. This means 3-year-old Joshua repeatedly kicks the dog and shakes uncontrollably. Grayson, the 4-year-old, is a kicker and headbanger if his waffle isn't right. Jay, the 5-year-old, punches holes in the wall and has destroyed two ceiling fans.
Lambert-Power, whose two biological children are 13 and 16, said the boys' behavior is far beyond that of normal preschoolers. "Sometimes you just have to sit down and hold them so they don't harm themselves," she said.
Jay had been on Risperdal about six months when state reviewers stopped it in December. After two weeks of pleading by the pediatrician and the mother, who was fielding angry calls from Jay's kindergarten teacher, Medicaid approved the drug for all three boys.
"Now they are able to process things better, rather than jumping on the impulse wagon," Lambert-Power said. "It seems to level them out."
Nor is she overly concerned about long-term side effects of the drugs. "I'm more worried about how they can harm themselves now.''
Times computer-assisted reporting specialist Connie Humburg contributed to this report. Kris Hundley can be reached at firstname.lastname@example.org or (727) 892-2996.