Weight Gain Associated With Antipsychotic Drugs

Young children and adolescents who take the newest generation of antipsychotic medications risk rapid weight gain and metabolic changes that could lead to diabetes, hypertension and other illnesses, according to the biggest study yet of first-time users of the drugs.

The study, to be published Wednesday in The Journal of the American Medical Association, found that 257 young children and adolescents in New York City and on Long Island added 8 to 15 percent to their weight after taking the pills for less than 12 weeks.

The patients, ages 4 to 19, added an average of one to one-and-a-half pounds a week.

“The degree of weight gain is alarming,” said Dr. Wayne K. Goodman, head of a Food and Drug Administration advisory panel on the drugs last summer and chairman of psychiatry at Mount Sinai School of Medicine in Manhattan. “The magnitude is stunning,” he said.

Although the drugs’ influence on weight and metabolism had been previously detected, Dr. Goodman, who was not involved in the study, said the speed and magnitude of the effects found in the study were greater than previously reported — findings he said were made possible by looking exclusively at new patients.

The four drugs in the study, the most popular antipsychotic medications, are industry blockbusters, with combined sales of $12.7 billion last year. And while all four caused weight gain, there were differences in the extent of the side effects. Among them, Zyprexa, made by Eli Lilly & Company, showed the most severe effects on weight and metabolism. The study’s authors, and an accompanying JAMA editorial, called for closer monitoring of patients taking the drugs, as well as additional long-term studies.

The drugs are prescribed for schizophrenia, bipolar disorder and a broad range of less serious psychological conditions. Their use by children and teenagers has been rising steadily. A 2008 study found that patients under 19 years old accounted for 15 percent of antipsychotic drug use in 2005, compared with 7 percent in 1996.

The study, financed by federal grants, is the largest yet published on childhood use of the drugs. And because it is also the largest study of first-time users of the drugs, whether children or adults, it provided an opportunity to analyze the cause and severity of near-term side effects.

As a result, the study goes further than previous research in distinguishing varying metabolic effects among the four drugs, according to Dr. Judith L. Rapoport, another expert who was not involved in the research.

“It’s by far the best documentation of not just weight gain and metabolic changes but also suggesting there might be differences among the drugs,” Dr. Rapoport, chief of the child psychiatry branch at the National Institute of Mental Health, said in an interview.

The lead researcher, Dr. Christoph U. Correll of Zucker Hillside Hospital in Queens and the Feinstein Institute for Medical Research in Manhasset, N.Y., said researchers had saved their blood work for future study of the molecular basis of the different drugs’ metabolic effects.

“People should think twice before they actually prescribe the medications,” Dr. Correll said in a phone interview. The drugs studied are in a class known as atypical antipsychotics, which are second-generation psychiatric drugs that in some cases regulate the receptors in the brain that interact with the mood-altering hormones serotonin and dopamine.

Abilify and Risperdal are the only two of the four drugs approved as pediatric treatments, for the severe mental conditions schizophrenia and bipolar disorder — and in Risperdal’s case, for some children with autism. More than 70 percent of atypical antipsychotics’ use in young children and teenagers has been off-label prescriptions for nonpsychotic conditions like attention deficit hyperactivity disorder, according to Stephen Crystal, a Rutgers University professor who studies the drugs.

Dr. Rapoport said Lilly’s Zyprexa drug, introduced in 1996, had been so heavily marketed that it was in widespread use before physicians began to recognize the severity of its side effects a few years ago. Zyprexa has continued selling in the range of nearly $3 billion a year in the United States even as concerns emerged about its tendency to cause patients to gain weight.

Abilify, from Bristol-Myers Squibb, showed the least metabolic effects among the four drugs in the study. “It’s considered a very good but weaker drug,” Dr. Rapoport said.

The other two drugs in the study, whose weight-related side effects fell between Zyprexa and Abilify, were Risperdal and Seroquel. Seroquel, from AstraZeneca, had United States sales of $2.2 billion in the first six months of this year, according to IMS Health, a research company. Abilify had sales of $1.9 billion during that period; Zyprexa, $1.5 billion; and Risperdal, from Johnson & Johnson, $660 million.

A Lilly spokesman, Jamaison R. Schuler, said the new research echoed Lilly’s own findings and previous studies about weight gain and metabolic changes that led to a label warning being placed on Zyprexa in October 2007. But in an interview, he said the drug was still essential to sparing children a lifetime of psychological suffering.

“It’s important to recognize that severe mental illnesses, including schizophrenia and bipolar 1 disorder, often strike during adolescence and are devastating,” Mr. Schuler said.

In an editorial accompanying the study in the journal, Dr. Christopher K. Varley and Dr. Jon McClellan, child psychiatrists at Seattle Children’s Hospital and the University of Washington school of medicine, wrote that “ominous long-term health implications” arise from weight gain and changes in blood fat levels early in life. “These results challenge the widespread use of atypical antipsychotic medications in youth,” they wrote.

Dr. Varley said in a phone interview Monday that doctors had been loath to use the older antipsychotic medicines, like Thorazine and Haldol, because of neurological side effects. But he said the new data indicated that the newer ones should be prescribed more cautiously.

“In the course of less than 12 weeks, the weight gains are startling,” he said. “If you look at Zyprexa, the kids are gaining a pound and a half a week. Even with the drug Abilify, which is one that was not so prone to weight gain, kids still gained a pound a week. In addition, they had evidence in a very short period of time of other metabolic problems.”

The study covered 272 patients visiting clinics in Brooklyn, Queens and Long Island from 2001 to 2007. Fifteen patients who stopped taking their medicine were used as a control group. Their weight stayed level. The 257 patients who stayed on their drugs took detailed tests, including a fasting blood test to check for high glucose levels.

Their mean weight at the start of the study period was 118 pounds. But after about 11 weeks, those who took Zyprexa had gained 18.7 pounds; Seroquel, 13.4 pounds; Risperdal, 11.7 pounds; and Abilify, 9.7 pounds.

Their waists typically expanded three inches with Zyprexa, and two inches with the others.

All but Abilify showed rapid and significant increases in one or more metabolic markers, which can presage adult obesity, hypertension and Type 2 diabetes. The metabolic markers included glucose, insulin, triglycerides and cholesterol.

The authors noted that the study had limitations. Patients were not randomly assigned, so the baseline starting weights differed. Clinicians, given the choice, started heavier patients on Seroquel and those with the lowest fat mass on Zyprexa, who then gained the most, the data show. Also, the study did not control for dosing or other medications, which can affect outcome.

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Antipsychotic Drugs Prescribed to Kids Get More Scrutiny

Alison Bass directs our attention to the tragic story of Denis Maltez, a 12-year-old Miami boy who died of serotonin syndrome after being given two anti-psychotic medications (Seroquel and Zyprexa) plus an anti-seizure drug and tranquilizer. Serotonin syndrome occurs when a combination of drugs causes the brain to produce excess serotonin. Denis had severe autism and was living in a Rainbow Ranch group home; the lawsuit just filed by his mother, Martha Quesada, says the drugs were used as a “chemical restraint to control Denis’s behavior.” Florida shut down Rainbow Ranch shortly after Denis’s death.

Denis is not the only child to have died after being given a cocktail of psychiatric drugs. In 2006, 4-year-old Rebecca Riley died from an overdose of drugs prescribed for bipolar disorder and ADHD. The Wall Street Journal’s David Armstrong reports that prescriptions of psychiatric drugs for children increased 44.6% between 2002 and 2007, and many of these drugs are not approved for use in children. The good news is that since Riley’s death, states are increasing scrutiny of psychiatric drugs prescribed for children, and this scrutiny is starting to have an effect. Armstrong writes:

Some states began moving to require special approval before they would cover a
claim for an antipsychotic. A group of 16 states started studying the use of
psychiatric medication in children in 2007 in an effort they dubbed “too many,
too much, too young,” says Jeffrey Thompson, the medical director of the
Washington state Medicaid program.

In California, the number of children
six and under using psychiatric medications has fallen to 4,200 from 5,686 since
a 2006 prior-authorization plan was put in place, the state’s top Medicaid
official says.

Florida’s state Medicaid agency says the number of
prescriptions for atypical antipsychotics written for children under age six in
the second half of last year dropped to 1,137 from 3,167 a year earlier.

The agency says the decline was the result of a state program started
last year under which prescriptions for children under six are reviewed for
appropriateness by state-hired psychiatric consultants before Medicaid will
cover them.

Washington has created a system to flag the use of
psychiatric drugs that may contain too high a dose for young children or have
side effects that it regards as particularly dangerous. From May 2006 to April
2008, the system flagged 1,032 cases for review by outside consultants.

Attorneys general from 11 states are also investigating Eli Lilly for allegedly marketing its antipsychotic Zyprexa for non-approved uses; the company has already agreed to a $1.4-billion settlement over its marketing of the drug.

In her post about Denis Maltez’s death, Alison Bass brings us back to the larger question:

Why, you might ask, do some psychiatrists prescribe these potentially lethal
drugs to young children and then not monitor them for side effects? I can’t
answer that question. What I do know is that many doctors and consumers think
these drugs are safe and effective for such off-label uses in large part because
drug companies have paid big bucks both to KOLs [Key Opinion Leaders] and
“patients” like Andy Behrmann and Jim McNulty to shill for them. And that’s
precisely why we need public disclosure laws like the one that the Vermont
Legislature passed this week — see New York Times article here — so that
everyone knows who the shills are and can take what they say with a hefty dose
of skepticism. Here’s hoping Congress passes the Physician Payment Sunshine Act
and makes this a national trend.

The new Vermont law she references requires pharmaceutical companies to publicly disclose all payments given to healthcare providers with prescribing authority, and it bans nearly all gifts (including free meals) given to healthcare providers and other health-related staff. Vermont already requires pharmaceutical companies to report marketing expenses, but the new legislation closes a loophole that had allowed companies to use the “trade secret” designation to keep some expenses private.

Minnesota already requires pharmaceutical companies to report their payments to healthcare providers, and these reports are made available to the public. In 2007, New York Times reporters Gardiner Harris, Benedict Carey, and Janet Roberts analyzed Minnesota’s records and found a correlation between financial relationships between doctors and pharmaceutical companies and an increase in the prescriptions of atypical antipsychotics for children:

From 2000 to 2005, drug maker payments to Minnesota psychiatrists rose more than
sixfold, to $1.6 million. During those same years, prescriptions of
antipsychotics for children in Minnesota’s Medicaid program rose more than
ninefold.

Those who took the most money from makers of atypicals tended
to prescribe the drugs to children the most often, the data suggest. On average,
Minnesota psychiatrists who received at least $5,000 from atypical makers from
2000 to 2005 appear to have written three times as many atypical prescriptions
for children as psychiatrists who received less or no money.

The article goes on to note that “no one has proved that psychiatrists prescribe atypicals to children because of drug company payments,” and that some prescribers of these drugs for children receive no payments from the pharmaceutical industry.

There are many reports of children with serious mental health issues benefiting from psychiatric drugs; it’s likely that for many children, the benefits of atypical antipsychotics outweigh the risks, which include “rapid weight gain and blood sugar problems, both risk factors for diabetes; disfiguring tics, dystonia and in rare cases heart attacks and sudden death in the elderly.” For other patients, less-risky treatments might also be effective and should be tried first. The drop in psychiatric-medication prescriptions for children in states that have instituted prior authorization suggests that prior to these programs, some doctors were writing these prescriptions without have first tried these less-risky options.

Increased scrutiny from regulators responding to disturbing trends seems to be improving prescribing practices around psychiatric drugs for children. Increased transparency in Minnesota has enabled journalists to draw attention to potential conflicts of interest, which can prompt doctors to examine their own prescribing behaviors and may result in additional regulatory measures. When it comes to drugs that can result in serious health problems and even death, vigilance and transparency are key.


Sourec : thepumphandle.wordpress.com

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