Feb. 17, 2008
By Karl Stark
CHIP ELLIS / For The Inquirer
Tammy Wandling of West Virginia hired legal counsel in Philadelphia after son Austin developed a growth in his breast while taking Risperdal for autism.
SARAH J. GLOVER / Inquirer Staff PhotographerJohn Huff of Pleasantville, N.J., required surgery to remove the female-size breasts he developed at 14 while on Risperdal.
SARAH J. GLOVER / Inquirer Staff PhotographerJohn Huff, 17, of Pleasantville, N.J., took the antipsychotic Risperdal for seven years for behavioral problems. "He would ask me 'Am I a girl?' said his mother, Nicola. A spokeswoman for Risperdal's maker, Janssen, said the side effect was rare.
When they were first introduced in the early 1990s, new antipsychotic medications for severe mental illness were seen as wonder drugs that were safer and more effective than their predecessors. Sales soared as doctors tried them on new conditions, including dementia, aggression and other behavioral problems. Children and the elderly were among the biggest users.
But now, several studies questioning some of the drugs' benefits have led many doctors to talk of using them for shorter periods and with tighter monitoring, because of side effects that include sedation, obesity and diabetes.
"You can't just pop someone on it and see them in a year," said Jason Karlawish, a geriatric psychiatrist at the University of Pennsylvania.
These drugs, known as atypical antipsychotics, offer a contentious case study of a common pattern in pharmaceuticals. New drugs are typically approved for narrow uses and get tried off-label on conditions that are difficult to treat. Companies' sales efforts stoke up overall use until the research catches up years later, dulling the early enthusiasm. While some patients are helped, lawsuits are also a common legacy.
The atypicals were originally approved for severe mental illness - schizophrenia and bipolar disorder - which had limited markets.
But under a determined marketing effort portraying them as safer and more effective than their predecessors, the atypicals came to be tried beyond their approved uses for nursing-home residents, prisoners, and children younger than 6 years old.
Total U.S. sales for the class reached $13 billion in 2007, doubling sales of 2002, according to IMS Health Inc., a pharmaceutical-information firm. Atypicals carry such names as Risperdal, made by Janssen Pharmaceutica, part of Johnson & Johnson; Zyprexa from Eli Lilly & Co.; Seroquel by AstraZeneca P.L.C.; Geodon by Pfizer Inc.; and Abilify by Bristol-Myers Squibb Co.
All over the country, state officials are discovering that atypicals have become the largest drug class in Medicaid, the health program for the poor. And many state officials question whether that reflects overzealous marketing or real need. Several states, including Pennsylvania, are suing some drugmakers for allegedly promoting the drugs beyond approved uses and commissioning "ghost-written" articles to stoke use of the drugs.
The drugmakers reject the suits' claims and are obtaining new approvals from the Food and Drug Administration to treat more conditions. In the last two years, Janssen's Risperdal got approval to treat schizophrenia in adolescents and the irritability of autism in ages 5 to 16.
Atypicals remain a cornerstone of care for serious mental illness.
Ellen Sholevar, director of child and adolescent psychiatry at the Temple University School of Medicine, said atypicals could help children even though they had not been well-studied. Antipsychotics are used when young children appear to be out of control and represent a danger to themselves or others, or have "very severe disorders where there is no other viable treatment option," she said.
Naas Siddiqui, 25, of West Philadelphia, said that antipsychotics eased her manic symptoms and helped her graduate from Yale University in 2007.
While Zyprexa made her lethargic and gain weight, she said, Abilify calmed her. She gets her blood tested every six months and sees a physician more frequently.
"I don't want to stay on it permanently. But I think it's helped me significantly," she said.
A different view of the drugs came from Nicola Huff of Pleasantville, N.J., whose son, John Aaron, took Risperdal for seven years to resolve his behavioral problems.
But at age 14, he developed a well-known drug side effect: female-size breasts that had to be surgically removed."He would ask me 'Am I a girl?' And I would tell him 'no,' " Nicola Huff said.
Tammy Wandling, whose son Austin has autism, said a psychiatrist put him on Risperdal at age 4. In less than nine months, Austin developed a baseball-size growth in his right breast.
"I couldn't believe how big it was," said his mother, who lives near Charleston, W.Va.
Research suggests Risperdal, like the older antipsychotics, can cause an increase in the hormone prolactin, which directs breasts to enlarge and make milk. Risperdal's label warns about the possibility.
The experience helped drive both women to hire Steve Sheller and James J. Pepper, both Philadelphia lawyers.
"They're being given an easy out with a pill. But the easy out may create a much more serious problem," Sheller said.
A spokeswoman for Risperdal's maker, Janssen, rejected the claims and said the side effect was rare.
Experts say the condition can be avoided by close monitoring or by switching to another antipsychotic.
The drugmakers still face vast legal threats.
Zyprexa-maker Lilly has set aside $1.2 billion to settle 31,000 claims, mostly about whether the firm failed to warn patients of diabetes in package inserts before 2003.
Lilly still faces 1,200 cases as well as a federal probe over its marketing of Zyprexa.
Much litigation has focused on how doctors have prescribed antipsychotics beyond their approved use. Doctors may prescribe off-label, and have done so for dementia, attention deficit, aggression, autism and post-traumatic stress disorder.
But firms are not allowed to promote off-label uses.
Bristol-Myers Squibb, maker of Abilify, agreed last year to pay $515 million in part to settle allegations that it improperly promoted the antipsychotic for off-label uses.
The firms also face thousands of additional claims. AstraZeneca, for example, said it had 8,000 suits pending for Seroquel.
It was not always that way. The first antipsychotics, including Thorazine, helped free many people from state hospitals. But that generation came with severe side effects, including the involuntary and debilitating movements called tardive dyskinesia.
The second generation, dubbed atypicals, began appearing in the 1990s.
They are thought to cause fewer involuntary movements and other severe effects. But they are more likely to cause weight gain and diabetes, said Tom Clark, director of clinical affairs for the American Society of Consultant Pharmacists Foundation.
"There's more awareness of the risks of these drugs," Clark added. "There's a tendency to more caution."
Amy Brodkey, a Philadelphia psychiatrist, agreed, saying she and her colleagues use antipsychotics, with more monitoring. "Everybody is thinking about it a lot more," she said.
Some of the dramatic sales growth has come in nursing homes, where the drugs are used to combat the delusions and aggressiveness that often accompany dementia.
Such behavior is one of the thorniest problems in geriatrics and often becomes the tipping point that sends patients into nursing homes.
More than 26 percent of the nation's nursing-home residents were on antipsychotics in early 2007. That compares with 19.4 percent in 1999, federal surveys show.
U.S. Sen. Charles Grassley (R., Iowa) has asked the government to review how antipsychotic drugs are being used off-label in nursing homes, and whether residents are being sedated unnecessarily.
Those drugs do little to help dementia patients, said Lon S. Schneider, a California psychiatrist and lead investigator of the CATIE-AD study of outpatients with Alzheimer's. He and his colleagues found that patients on antipsychotics for 12 weeks had a slightly greater risk of dying sooner than those on placebo.
While actual deaths were rare, physicians should monitor the drugs more closely and stop them when they do not seem to help, he said.
Antipsychotic use also has exploded in young people. Doctor visits with antipsychotic prescriptions became six times more common from 1993 to 2002 in people 20 and younger, according to a study led by Columbia University psychiatrist Mark Olfson.
"I've seen the growth of these agents for several years," added Mark Helm, a pediatrician in Arkansas, where the state attorney general is also suing a maker of an antipsychotic drug.
In Pennsylvania, Medicaid in 2006 paid for atypicals for at least 824 children under the age of 6, said Terri Cathers, director of pharmacy for Medicaid. Both Pennsylvania and New Jersey have hired a firm, Comprehensive NeuroScience Inc., to identify unusual prescriptions and send doctors letters about the use.
"We want to make sure all other avenues are exhausted before they resort to putting children on these drugs," Cathers said.