Yourlawyer.com (Adderall News)

ADHD Drug Study Finds Heart Death Risks for Kids, But FDA Says Recommendations Won't Change

Tue, 16 Jun 2009 00:00:00 -0700

While a new study has found that stimulant medications used to treat attention-deficit hyperactivity disorder (ADHD) may increase the risk of sudden cardiac death in children, the Food & Drug Administration (FDA) is not changing its recommendations on the way such drugs are prescribed. According to a posting on its website, the agency is asserting that the study had "limitations" that makes it difficult to draw conclusions about the drugs' risks.

Labeling for drugs like Ritalin, Adderall, Dexedrine, and Concerta already include warnings about the risk of sudden cardiac death in patients with heart problems, but they have been considered safe for children who don't have pre-existing heart conditions. There have been worries, however, that such stimulants could be risky in children with undiagnosed heart problems. It is not known how often cardiac events occur in children taking these drugs.

According to a report on WebMD, concerns about the drugs' heart risks were raised in 2006, when an FDA panel reported that between 1992 and 2005, 11 sudden cardiac deaths occurred in children taking Ritalin and Concerta, and 13 sudden cardiac deaths occurred among children taking Adderall and Dexedrine. Last year, the American Heart Association recommended screening all children and teens taking ADHD drugs for hidden heart problems, as well electrocardiogram screening of all patients being placed on the stimulants for the first time, WebMD said.

This latest study on ADHD stimulant drugs, which was published in the American Journal of Psychiatry, did find a slight increase in the risk of sudden cardiac death among children and teens taking the medications. The study was funded by the FDA and the National Institute of Mental Health.

According to the FDA, the study compared the use of stimulant medications in 564 healthy children from across the United States who died suddenly, most likely due to sudden cardiac disturbance, to the use of stimulant medications in 564 children who died as passengers in a motor vehicle accident. According to the study report, out of the children who died suddenly, 10 were reported to be taking a stimulant medication at the time of death. Out of those who died in a motor vehicle accident, two were reported to be taking a stimulant medication at the time of death. Researchers concluded that the odds of using stimulant medication were six to seven times greater among the children who died suddenly of unexplained causes than among those who died in car crashes.

However, the FDA maintains that the study had several limitations, including the significant time lag between when the deaths occurred and when the information was collected. Given such limitations, the FDA said it is unable to conclude that the data presented in the study affect the overall risk-and-benefit profile of stimulant medications used to treat ADHD in children. The agency said that parents should not stop a child’s stimulant medication based on the study. Instead, parents should discuss concerns about the use of these medications with the prescribing health care professional, FDA said.

According to report in the Los Angeles Times, for more conclusive answers, parents of ADHD children are going to have to wait for the results of two more studies due to be released next fall and winter. Those studies will look at rates of heart attack and stroke in children and adults who take stimulant medication for ADHD and compare them to cardiovascular events in populations not on ADHD medication, the Times said.

ADHD Study Stirs Controversy

Fri, 27 Mar 2009 00:00:00 -0700

The safety and effectiveness of medications used to treat attention-deficit hyperactivity disorder (ADHD) are being questioned with the release of new study data that shows such drugs to be ineffective - and possibly harmful - in the long term. According to The Washington Post, the findings are also raising questions about the conduct of some involved in the research, because they are very different than initial findings that were released in 1999.

The study, known as the Multimodal Treatment Study of Children (MTA), was designed to test whether children diagnosed with ADHD do better when treated with drugs, with drugs plus talk therapy, with talk therapy alone or with routine medical care alone.

According to the Washington Post, the initial results published over a decade ago showed clearly that those treated with medication did much better than those who got only talk therapy or routine care. Drug makers, of course, took advantage of the findings, and used the initial results in promotional materials. And according to The Post, the study's initial findings resulted in treatment being skewed in direction of medication.

The first follow-up results were issued in 2007. They no longer showed differences in behavior between children who were medicated and those who were not. What's worse, the study also showed that children on drugs for three years were shorter and lighter than their non-medicated counterparts.

But according to The Post, those results were presented in a more positive light in a July 2007 news release issued by the National Institute of Mental Health. And instead of saying that the growth of medicated kids was stunted, the release said that non-medicated children “grew somewhat larger.”

The positive presentation of the MTA study most likely encouraged the increased use of ADHD medications. In 2004, physicians wrote 28.3 million prescriptions for ADHD drugs; last year, they wrote 39.5 million, The Post said.

According to The Washington Post, over the past several years, the study continued to show little difference between medicated and non-medicated children. Some of data were published online Thursday in the Journal of the American Academy of Child and Adolescent Psychiatry.

One principal scientist in the study, psychologist William Pelham, told the Post that the most obvious interpretation of the data is that the medications are useful in the short term but ineffective over longer periods. But Pelham claims his colleagues had repeatedly sought to explain away evidence that challenged the long-term usefulness of medication, the Post said.

"The stance the group took in the first paper was so strong that the people are embarrassed to say they were wrong and we led the whole field astray," Pelham, of the State University of New York at Buffalo, told the Post. "If 5 percent of families in the country are giving a medication to their children, and they don't realize it does not have long-term benefits but might have long-term risks, why should they not be told?"

American Children Take the Most Psychotropic Drugs

Fri, 26 Sep 2008 00:00:00 -0700

A new study reports that American children are about three times likelier to be prescribed psychotropic medications than children in Europe. The study states that the differences may be attributable to regulatory practices and cultural beliefs about the role of medication in emotional and behavioral problems.

Julie Zito led the team comprised of researchers from the U.S., Germany, and the Netherlands. The group investigated prescription levels in the three countries. Zito reported that, "Antidepressant and stimulant prevalence were three or more times greater in the U.S. than in the Netherlands and Germany, while antipsychotic prevalence was 1.5 to 2.2 times greater." The use of antidepressants, such as Prozac, and stimulants, such as Ritalin, in children has been the subject of much controversy; this study is believed to quantify the differences in practice between the US and Western Europe.

Study authors believe the differences may be partly due to different diagnostic classification systems. For instance, "The US trend of increasing bipolar diagnosis in children and adolescents does not reflect European practice." The team also discussed government cost restrictions in Europe, the increased amount of child psychiatrists per capita in the U.S., as well as the U.S. practice of using two or more different psychotropic drugs in a single year as possible explanations. "Direct to consumer drug advertising, which is common in the U.S., is also likely to account for some of the differences. The increased use of medication in the US also reflects the individualist and activist therapeutic mentality of US medical culture," Zito added.

Earlier this month we reported about one million children and teenagers are treated for schizophrenia and prescription rates for atypicals—the anti-psychotic drugs most prescribed for these disorders—have increased more than five-fold for children over the past 15 years and are also being used to control outbursts and aggression in children with a wide variety of diagnoses representing about 80 percent of the prescriptions written for maladies such as autism, ADHD, bipolar disorder, depression, and anxiety, despite the drugs’ serious side effects. Some uses are off-label, or not approved by the Food and Drug Administration (FDA). Approximately three million Americans suffer from schizophrenia and about 20 percent begin to show symptoms as children or teens.

Meanwhile, state officials are finding atypical antipsychotics have become the largest drug class in Medicaid and many question if this is due to marketing or need; several states are suing drug makers for off-label promotion and commissioning "ghost-written" articles to increase use. But, drug makers continue to obtain new approvals from the FDA to treat more conditions. In the last two years, Risperdal received approval to treat schizophrenia in adolescents and the irritability of autism in children ages five to 16. Nicola Huff, whose son, John Aaron, took Risperdal for seven years to resolve behavioral problems said at age 14, he developed female-sized breasts that had to be surgically removed. Tammy Wandling, whose son Austin has autism, said a psychiatrist put him on Risperdal at age four. In less than nine months, Austin developed a baseball-size growth in his right breast. Research suggests Risperdal can cause an increase in the hormone prolactin, which causes breasts to enlarge and produce milk.

Screen for Kids for Heart Problems Before Prescribing ADHD Drugs, Heart Group Says

Tue, 22 Apr 2008 00:00:00 -0700

Children with Attention Deficit Hyperactivity Disorder (ADHD) should be screened for heart problems before they are prescribed stimulant drugs like Ritalin, the American Heart Association has warned. About 2.5 million American children and 1.5 million adults take stimulants such as Ritalin, Adderall and Concerta to control the symptoms of ADHD. Such drugs are known to increase heart rates, a side effect that can be dangerous - and even deadly - if a patient has an undetected heart condition.

ADHD is a condition that becomes apparent in some children in the preschool and early school years. It is hard for these children to control their behavior and/or pay attention. It is estimated that between 3 and 5 percent of children have ADHD, or approximately 2 million children in the United States. Stimulants, like Adderall and Ritalin, are known to raise blood pressure. In 2006, the FDA added a “black box” warning to the labels of ADHD drugs warning of cardiovascular risks associated with the medications. The heart-related problems cited by the new warning included sudden death in patients who have heart problems or heart defects; stroke and heart attack in adults; and increased blood pressure and heart rate.

Last December, the journal "Pediatrics" published a study that suggested such medications do cause some heart symptoms. The study that looked at data on 55,383 Florida children ages 3 to 20 years who had ADHD. About 59 percent were taking a stimulant medication during the study period (1994 to 2004). Children taking a stimulant to control ADHD symptoms were 20 percent more likely to visit an emergency clinic or doctor’s office with heart-related symptoms, such as a racing heartbeat, than children who had never used or discontinued treatment. However, rates of death or hospital admission for serious heart conditions were no different than the national rates among the general population.

Despite the apparent good news on serious heart conditions and deaths related to ADHD stimulants, the authors of the “Pediatrics” article asserted that there was a great need for more research on the long-term effects of these drugs. Given that 3 to 4 million children take stimulant medications like Ritalin to control symptoms of ADHD, they wrote that further studies need to be done to determine the consequences of chronic stimulant use during childhood on heart disease in adulthood.

The American Heart Association is now recommending that doctors conduct a thorough exam, including a family history and an EKG, before children are put on the drugs to make sure that they don't have any undiagnosed heart issues. "We don't want to keep children who have this from being treated. We want to do it as safely as possible." said Dr. Victoria Vetter, a pediatric cardiologist at the University of Pennsylvania School of Medicine and head of the committee making the recommendation.

An EKG can detect abnormal heart rhythms that can lead to sudden cardiac arrest. Children who are already on ADHD drugs should also be tested, the heart group said. With careful monitoring by a pediatric cardiologist, children with heart problems can take the medicines if necessary.

ADHD Stimulant Drugs Tied to ER Visits for Heart Symptoms

Tue, 11 Dec 2007 00:00:00 -0800

Adderall, Ritalin and other stimulants used to treat Attention Deficit Hyperactivity Disorder (ADHD) could be responsible for sending hundreds of people to the emergency room each year with heart related symptoms, a new study says. This latest study of ADHD drugs was the first to look at potential heart problems linked to the medications since the Food & Drug Administration (FDA) updated their labels last year to include heart warnings.

ADHD is a condition that becomes apparent in some children in the preschool and early school years. It is hard for these children to control their behavior and/or pay attention. It is estimated that between 3 and 5 percent of children have ADHD, or approximately 2 million children in the United States. Stimulant medications like Ritalin are known to improve ADHD symptoms, but they come with side effects.

Stimulants, like Adderall and Ritalin, are known to raise blood pressure. In 2006, the FDA added a “black box” warning to the labels of ADHD drugs warning of cardiovascular risks associated with the medications. The heart-related problems cited by the new warning included sudden death in patients who have heart problems or heart defects; stroke and heart attack in adults; and increased blood pressure and heart rate.

Until now, no long term studies had been done on the heart risks associated with Ritalin, Adderall and other ADHD stimulants. Now, new research published in the journal “Pediatrics” suggests that such medications do cause some heart symptoms. The article details a study that data on 55,383 Florida children ages 3 to 20 years who had ADHD. About 59 percent were taking a stimulant medication during the study period (1994 to 2004). Children taking a stimulant to control ADHD symptoms were 20 percent more likely to visit an emergency clinic or doctor's office with heart-related symptoms, such as a racing heartbeat, than children who had never used or discontinued treatment. However, rates of death or hospital admission for serious heart conditions were no different than the national rates among the general population.

Despite the apparent good news on serious heart conditions and deaths related to ADHD stimulants, the authors of the “Pediatrics” article asserted that there was a great need for more research on the long-term effects of these drugs. Given that 3 to 4 million children take stimulant medications like Ritalin to control symptoms of ADHD, they wrote that further studies need to be done to determine the consequences of chronic stimulant use during childhood on heart disease in adulthood.

This is not the first time the safety of ADHD drugs have been called into question. A small study conducted by he University of Texas and the M.D. Anderson Cancer Center found a link between Ritalin and increased risk of cancer. While this research only involved 12 children, those taking Ritalin all experienced a significant increase in the chromosomal abnormalities associated with an a higher chance of developing cancer. Other known side effects of ADHD stimulants include loss of appetite, abdominal pain, sleep problems and headaches.

ADHD drugmakers must tell of risks

Fri, 23 Feb 2007 00:00:00 -0800

Federal officials told the makers of Ritalin, Adderall, Strattera and all other drugs for treatment of attention deficit hyperactivity disorder, or ADHD, on Wednesday to come up with new pamphlets to explain the potential risks of the drugs to patients and parents.

The announcement came almost a year after panels of Food and Drug Administration advisers recommended that informational guides be provided to consumers. There are 15 drugs to treat ADHD, including extended-release, patch and chewable versions.

The panels made the recommendation after reviewing reports of young children hearing voices or having hallucinations while on the medications, some reporting they could see snakes or bugs or worms, and there were other reports of heart complications, including sudden death.

An agency review found a slightly increased risk, about one per 1,000 patients for adverse psychiatric reactions. A separate review of reports of serious cardiovascular adverse events found reports of sudden death in patients with underlying serious heart problems or defects, and reports of stroke and heart attack in adults with certain risk factors.

The new patient guides would supplement the information already included on the drugs' labeling and would be given out in booklet or pamphlet form with each prescription.

Dr. Mark Epstein, a specialist in the treatment of ADHD and medical director of the Miami Children's Hospital Dan Marino Center in Weston, Fla., said the concerns first surfaced about two years ago and that he got calls from many parents of his patients who take the drugs.

"Parents are very scared when they hear about a risk for sudden death," Epstein said. But after he explained that the risk is no higher for children on the drugs than for the general population, and that the deaths occurred in patients with known heart problems or a family history of such problems, only one or two parents insisted their children be taken off the drugs, he said.

"When the appropriate diagnosis is made and the medications are prescribed properly, they are exceedingly safe," Epstein said, but he recommended that patients and parents talk with their own doctors if they have concerns.

ADHD affects an estimated 3 percent to 7 percent of school-age children and about 4 percent of adults. The three main symptoms are inattention, hyperactivity and impulsivity.

Government wants further ADHD drug warnings

Thu, 22 Feb 2007 00:00:00 -0800

The makers of Ritalin, Adderall, Strattera and other drugs treating attention-deficit hyperactivity disorder were advised by the government Wednesday to give patients and their parents an additional warning that those medicines could cause serious psychiatric and heart problems, including sudden death.

Patients would receive with their prescriptions two-page "medication guides" that warn about possible side effects and urge them to notify doctors immediately after any sign of heart or psychiatric problems, such as chest pain, shortness of breath, fainting or hallucinations.

Dr. Thomas Laughren of the Food and Drug Administration emphasized that the move was precautionary and should not frighten patients away from taking the drugs, which he said were safe. He expected the manufacturers of the 15 drugs to comply with the request within 30 days.

An estimated 3.3 million children and 1.5 million adults take ADHD drugs, whose sales exceed $3.5 billion a year. Their use has been dogged by concerns about overuse in children and side effects, prompted by scattered reports of children dying suddenly. Some of the children were later determined to have had heart defects.

The latest action expands upon a move the government made last year, when the FDA asked manufacturers to revise ADHD drug labels to alert prospective patients with heart problems and warn of hallucinations in one out of 1,000 children.

Dr. Richard L. Gorman, a pediatrician who served on an FDA advisory panel that recommended the ADHD drug warnings, said the medication guides were "in line with" what the committee recommended. Gorman said parents must pay close attention to their children's reactions to the drugs because children might take them for years.

Laughren said it took until now to work out the wording of the medication guides, which are more simply worded than drug labels. Companies may tweak the language that the FDA proposed, he added.

More than 2,500 children who took ADHD drugs went to emergency rooms in 2004, and about a quarter of them had serious heart or blood pressure problems, the Centers for Disease Control and Prevention reported last year. Twenty-five deaths, 19 involving children, linked to the drugs were reported to the FDA from 1999 to 2003. Fifty-four strokes, heart attacks and other heart issues were also reported; some of those patients had previous heart conditions.

ADHD drug makers to warn of side effects

Wed, 21 Feb 2007 00:00:00 -0800

Drugs prescribed to treat attention deficit hyperactivity disorder will include guides to alert patients and parents of the risks of mental and heart problems, including sudden death.

The Food and Drug Administration said Wednesday that it directed the manufacturers of Ritalin, Adderall, Strattera and all other ADHD drugs to develop the guides. In May 2006, the agency told manufacturers to revise the labels of the drugs to reflect concerns about the cardiovascular and psychiatric problems.

Draft versions of the guides posted on the FDA Web site include discussion of reports of increased blood pressure and heart rate in ADHD patients, as well as cases of sudden death in some who have heart problems and heart defects. In adult patients, the reported problems also include stroke and heart attack.

The alerts also cover psychiatric problems, such as hearing voices, unfounded suspicions and manic behavior, of which there is a slightly increased risk in patients who take the drugs, the FDA said. The guides also tell patients and their parents of precautions they can take to guard against the risks.

Wednesday's announcement came roughly a year after two panels of FDA advisers recommended that the drugs include such patient medication guides. The announcement covers 15 drugs, including extended-release, patch and chewable versions of some of them.

Ritalin is manufactured by Novartis Pharmaceuticals Corp. and in generic form by other companies; Adderall is made by Shire Pharmaceuticals Inc.; Strattera by Eli Lilly & Co.

ADHD affects an estimated 3 percent to seven percent of school-age children and four percent of adults, the FDA said.

Drug makers to add warnings to ADHD pills

Wed, 21 Feb 2007 00:00:00 -0800

Drugs prescribed to treat attention deficit hyperactivity disorder will include guides to alert patients and parents of the risks of mental and heart problems, including sudden death.

The Food and Drug Administration said Wednesday that it directed the manufacturers of Ritalin, Adderall, Strattera and all other ADHD drugs to develop the guides. In May 2006, the agency told manufacturers to revise the labels of the drugs to reflect concerns about the cardiovascular and psychiatric problems.

Draft versions of the guides posted on the FDA Web site include discussion of reports of increased blood pressure and heart rate in ADHD patients, as well as cases of sudden death in some who have heart problems and heart defects. In adult patients, the reported problems also include stroke and heart attack.

The alerts also cover psychiatric problems, such as hearing voices, unfounded suspicions and manic behavior, of which there is a slightly increased risk in patients who take the drugs, the FDA said. The guides also tell patients and their parents of precautions they can take to guard against the risks.

Wednesday’s announcement came roughly a year after two panels of FDA advisers recommended that the drugs include such patient medication guides. The announcement covers 15 drugs, including extended-release, patch and chewable versions of some of them.

Ritalin is manufactured by Novartis Pharmaceuticals Corp. and in generic form by other companies; Adderall is made by Shire Pharmaceuticals Inc.; Strattera by Eli Lilly & Co.

ADHD affects an estimated 3 percent to seven percent of school-age children and four percent of adults, the FDA said.

ADHD Drugs to Get New Warnings

Wed, 21 Feb 2007 00:00:00 -0800

The U.S. Food and Drug Administration (FDA) announced today that it is ordering all manufacturers of attention deficit hyperactivity disorder (ADHD) medication to develop Patient Medication Guides to warn patients of potentially serious side effects. The most significant warnings will be related to adverse psychiatric symptoms and to cardiovascular risks.

“Medicines approved for the treatment of ADHD have real benefits for many patients but they may have serious risks as well,” said Dr. Steven Galson, director of the FDA’s Center for Drug Evaluation and Research (CDER). “In our ongoing commitment to strengthen drug safety, FDA is working closely with manufacturers of all ADHD medicines to include important information in the product labeling and in developing new Patient Medication Guides to better inform doctors and patients about these concerns.”

According to the agency, “An FDA review of reports of serious cardiovascular adverse events in patients taking usual doses of ADHD products revealed reports of sudden death in patients with underlying serious heart problems or defects, and reports of stroke and heart attack in adults with certain risk factors. Another FDA review of ADHD medicines revealed a slight increased risk (about 1 per 1,000) for drug-related psychiatric adverse events, such as hearing voices, becoming suspicious for no reason, or becoming manic, even in patients who did not have previous psychiatric problems.”

In May of 2006, the FDA’s Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee directed the drug makers to revise their label warnings, and the new directive for Patient Medication Guides is the next step in that process. There are 15 medications subject to the new warnings: Adderall, Adderall XR, Concerta, Daytrana, Desoxyn, Dexedrine, Focalin, Focalin XR, Metadate CD, Methylin Oral Solution, Methylin Chewable Tablets, Ritalin, Ritalin SR, Ritalin LA, and Strattera.

The FDA says that approximately 3 percent to 7 percent of children and 4 percent of adults suffer from ADHD, which has three main symptoms: inattention, hyperactivity, and impulsivity. They recommend that any patient considering using any of these drugs “develop a treatment plan that includes a careful health history and evaluation of current status, particularly for cardiovascular and psychiatric problems (including assessment for a family history of such problems).”

According to drafts of the medication guides posted on the FDA’s website, the warnings include information about adverse events including “heart-related problems” and “mental (psychiatric) problems.” The heart-related problems cited include sudden death in patients who have heart problems or heart defects; stroke and heart attack in adults; and increased blood pressure and heart rate. The psychiatric problems facing all patients include new or worse behavior and thought problems; new or worse bipolar illness; and new or worse aggressive behavior or hostility. For children and teenagers, there are added warnings about new psychotic symptoms (such as hearing voices, believing things that are not true, unfounded suspicion) or new manic symptoms.

FDA orders warning 'guides' for ADHD drugs

Wed, 21 Feb 2007 00:00:00 -0800

Pharmacists will soon begin handing out consumer-friendly "medication guides" about cardiovascular and psychiatric problems linked to widely prescribed attention deficit/hyperactivity disorder drugs, the Food and Drug Administration announced Wednesday.

Tom Laughren, director of the FDA's Division of Psychiatry Products, said makers of the 15 products approved to treat ADHD have 30 days to finalize the language in the medication guides. Meanwhile, drafts written by the FDA are posted online at www.fda.gov/cder/drug/ infopage/ADHD/default.htm.

About 3% to 7% of school-age children and about 4% of adults have attention disorders, the FDA says. In 2006, U.S. sales of ADHD drugs totaled about $3.5 billion, according to IMS Health, a health care information company.

Laughren said the new guides reflect changes ordered last May in the warnings section of the drugs' physician labeling. Two FDA advisory committees a year ago recommended adding information about new data on cardiovascular and psychiatric problems in children and teens who took the ADHD drugs.

From 1993 to February 2005, the FDA received 27 reports of unexpected death in patients under 18 who had taken one of the medications, Laughren said. It's not clear whether the deaths were the result of the ADHD drugs or underlying cardiovascular problems, he said.

In addition, since 2000 the agency has received hundreds of reports of psychosis or manic behavior, particularly hallucinations, in patients who had no known risk factors, according to an agency memo given last year to one of the advisory committees.

Also, a pooled analysis of trials that compared an ADHD drug with a placebo found a higher rate of hallucinations, delusions and mania in patients who were given the medication, Laughren said, putting the risk for such problems at one in 1,000 patients.

"Despite this new warning language in the medication guides; we continue to view ADHD as an important illness that benefits from treatment," Laughren said.

FDA Directs ADHD Drug Manufacturers to Notify Patients about Cardiovascular Adverse Events and Psychiatric Adverse Event

Wed, 21 Feb 2007 00:00:00 -0800

The U.S. Food and Drug Administration (FDA) today directed the manufacturers of all drug products approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) to develop Patient Medication Guides to alert patients to possible cardiovascular risks and risks of adverse psychiatric symptoms associated with the medicines, and to advise them of precautions that can be taken.

"Medicines approved for the treatment of ADHD have real benefits for many patients but they may have serious risks as well," said Steven Galson, M.D., Director, Center for Drug Evaluation and Research (CDER). "In our ongoing commitment to strengthen drug safety, FDA is working closely with manufacturers of all ADHD medicines to include important information in the product labeling and in developing new Patient Medication Guides to better inform doctors and patients about these concerns."

Patient Medication Guides are handouts given to patients, families and caregivers when a medicine is dispensed. The guides contain FDA-approved patient information that could help prevent serious adverse events. Patients being treated with ADHD products should read the information before taking the medication and talk to their doctors if they have any questions or concerns.

ADHD is a condition that affects approximately 3 percent to 7 percent of school-aged children and approximately 4 percent of adults. The three main symptoms are inattention, hyperactivity, and impulsivity. People with ADHD may have difficulty in school, troubled relationships with family and peers, and low self-esteem.

An FDA review of reports of serious cardiovascular adverse events in patients taking usual doses of ADHD products revealed reports of sudden death in patients with underlying serious heart problems or defects, and reports of stroke and heart attack in adults with certain risk factors.

Another FDA review of ADHD medicines revealed a slight increased risk (about 1 per 1,000) for drug-related psychiatric adverse events, such as hearing voices, becoming suspicious for no reason, or becoming manic, even in patients who did not have previous psychiatric problems.

FDA recommends that children, adolescents, or adults who are being considered for treatment with ADHD drug products work with their physician or other health care professional to develop a treatment plan that includes a careful health history and evaluation of current status, particularly for cardiovascular and psychiatric problems (including assessment for a family history of such problems).

As part of the Agency’s ongoing regulatory activity, in May 2006 the FDA directed manufacturers of these products to revise product labeling for doctors to reflect concerns about adverse cardiovascular and psychiatric events. These changes were based on recommendations from the FDA Pediatric Advisory Committee and the Drug Safety and Risk Management Advisory Committee. To help patients understand these risks, an additional part of this revised labeling process is the creation of a Patient Medication Guide for each individual product.

The medicines that are the focus of the revised labeling and new Patient Medication Guides include the following 15 products:

Adderall (mixed salts of a single entity amphetamine product) Tablets
Adderall XR (mixed salts of a single entity amphetamine product) Extended-Release Capsules
Concerta (methylphenidate hydrochloride) Extended-Release Tablets
Daytrana (methylphenidate) Transdermal System
Desoxyn (methamphetamine HCl) Tablets
Dexedrine (dextroamphetamine sulfate) Spansule Capsules and Tablets
Focalin (dexmethylphenidate hydrochloride) Tablets
Focalin XR (dexmethylphenidate hydrochloride) Extended-Release Capsules
Metadate CD (methylphenidate hydrochloride) Extended-Release Capsules
Methylin (methylphenidate hydrochloride) Oral Solution
Methylin (methylphenidate hydrochloride) Chewable Tablets
Ritalin (methylphenidate hydrochloride) Tablets
Ritalin SR (methylphenidate hydrochloride) Sustained-Release Tablets
Ritalin LA (methylphenidate hydrochloride) Extended-Release Capsules
Strattera (atomoxetine HCl) Capsules

Study: ADHD drugs send thousands to ERs

Wed, 24 May 2006 00:00:00 -0700

Accidental overdoses and side effects from attention deficit drugs likely send thousands of children and adults to emergency rooms, according to the first national estimates of the problem.

Scientists at the U.S. Centers for Disease Control and Prevention estimated problems with the stimulant drugs drive nearly 3,100 people to ERs each year. Nearly two-thirds overdoses and accidental use could be prevented by parents locking the pills away, the researchers say.

Other patients had side effects, including potential cardiac problems such as chest pain, stroke, high blood pressure and fast heart rate.

Concerns over those effects have led some doctors to urge the Food and Drug Administration to require a "black box," its most serious warning, on package inserts for drugs such as Ritalin, Concerta and Adderall. Yet even doctors advising the FDA don't agree on whether that's warranted.

The issue was discussed in a series of letters in Thursday's New England Journal of Medicine, including some from doctors worried about the dangers of not treating attention deficit hyperactivity disorder.

"The numbers (of side effects) are puny compared to the numbers of stimulant prescriptions per year," said Dr. Tolga Taneli, a child and adolescent psychiatrist at University of Medicine and Dentistry of New Jersey in Newark. "I'm not alarmed."

An estimated 3.3 million Americans who are 19 or younger and nearly 1.5 million ages 20 and older are taking ADHD medicines. Ritalin is made by Novartis Pharmaceuticals Corp. of East Hanover, N.J.; Concerta by Johnson & Johnson of New Brunswick, N.J., and Adderall by Shire US Inc. of Newport, Ky.

Twenty-five deaths linked to ADHD drugs, 19 involving children, were reported to FDA from 1999 through 2003. Fifty-four other cases of serious heart problems, including heart attacks and strokes, were also reported. Some of the patients had prior heart problems.

Still, there hasn't been a clear estimate of the scope of side effects. The CDC report, while not a rigorous scientific study, attempts to provide that by using a new hospital surveillance network.

From August 2003 through December 2005, the researchers counted 188 ER visits for problems with the drugs at the 64 hospitals in the network, a representative sample of ERs monitored to spot drug side effects.

Doctors linked use of stimulant ADHD drugs to 73 patients with side effects or allergic reactions. Another 115 accidentally swallowed ADHD pills, including a month-old baby, or took too much.

"These are cases where a young child took someone else's medication or they took too much of their own," CDC epidemiologist Dr. Adam Cohen said of the second group.

Nearly 1 in 5 patients was admitted to the hospital, 1 in 5 needed stomach pumping or treatment with medicines, and 1 in 7 had cardiac symptoms. Sixteen percent of the side effects involved interaction with another drug.

Besides cardiac problems, common symptoms included abdominal pain, rashes and spasms, pain or weakness in muscles, according to Cohen. No patients died.

Extrapolating to all U.S. hospitals, the researchers estimated 3,075 ER visits occur each year.

In another letter in the journal, the heads of the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry wrote they are concerned a black box warning would discourage use of ADHD drugs, raising patients' risks of academic failure, substance abuse and other problems.

This past February, an FDA drug safety advisory panel voted 8-7 for a black box warning. The next month, another FDA panel instead recommended data on cardiac and other risks go in a new "highlights" section the agency plans to add to the top of drug inserts.

Dr. Marsha Rappley, pediatrics professor at Michigan State University, and two other doctors on the advisory panels believe the vote for a black box was premature.

She said studies show the drugs raise blood pressure and pulse rates a bit, but it's unknown whether that would harm children taking them for years, and that cardiac risks may be higher for adults.

Dr. Steven Nissen, cardiology chief at the Cleveland Clinic, who had pressed for a black box warning at the FDA panel meeting, said ADHD drugs are powerful stimulants and inherently risky. Nissen and other doctors say the drugs are being prescribed to some who don't need them.

This week, the FDA said it is "working diligently" on "labeling changes that we feel accurately reflect the available data and the advice of the committees." The agency declined interview requests.

Ped Med: ADHD in the very young

Thu, 16 Feb 2006 00:00:00 -0800

Discerning behavior that portends attention-deficit/hyperactivity disorder presents challenges during the highly volatile first years of life.

"The range of symptoms is greatest in the youngest children: there is more impulsivity, low frustration tolerance, aggression than in older children," said ADHD investigator Donna Palumbo of the University of Rochester in New York. "It's much harder to diagnose preschoolers."

Because the diagnostic criteria call for symptoms that set the child back in at least two social settings, most youngsters do not qualify until they enter school, daycare, or some other arena that requires an engagement with their peers.

"We wouldn't interfere with infants or toddlers unless their behavior interfered with functioning, for example, if they were really aggressive," Palumbo said. "Most can do fine until they're around other children."

In her practice, Palumbo conducts behavior modification with parents, providing them with tools to deal with their child's disruptive deportment, before resorting to medication.

One of the theories she is testing in her investigation of 500 preschoolers is that such intervention with mom and dad might postpone, or even eliminate, the need to medicate the child.

A growing number of critics take issue with what they see as a tendency to over-prescribe potentially risky medications to children, particulary in view of the dearth of scientific evidence of the long-term effects of the drugs on developing bodies and brains.

The medicating of preschool minds comes under particularly harsh attack. Among the concerns is that this demographic, more than any other, has a wildly inconsistent response to the treatment.

A review of studies of 3-to-6-year-olds with ADHD, published in the Journal of Developmental and Behavioral Pediatrics, for example, shows this age group is more likely than its elders to experience a wide array of responses to and side effects from the stimulant drugs that comprise the single most popular first-line treatment of the disorder.

Keeping close tabs on any side effects is important, especially in view of a recent preliminary Food and Drug Administration report that drew a tentative link between stimulants and sudden deaths, strokes, heart attacks, high blood pressure and other serious complications in a small number of users, including children, although none was younger than 7.

Researchers stressed the results were tentative and theoretical. The review did not determine whether all the patients were actually taking the ADHD medicines at the time or account for such confounding factors as preexisting health conditions. However, the regulators considered the risk high enough to warrant immediate monitoring and further study.

Overall, 25 sudden deaths, including 19 in children ages 7 to 16, and 54 cases of serious, though not fatal, cardiovascular or cerebrovascular adverse events, 26 of them in minors under 18, occurred in patients taking the drugs between 1999 and 2003, according to the report. Those who died included 11 children treated with Adderall, one with Adderall XR, three with Ritalin, and four with Concerta, the study showed.

What role, if any, the drugs played is difficult to assess because some of the youngsters had underlying heart conditions that could have contributed to their demise, the report concluded.

Although the authors stressed no final conclusions about stimulant safety could be drawn from the analysis released Feb. 8, the following day an FDA panel took the highly unorthodox step of veering off its assigned course to call for strong new warnings on the drugs' labels and in their advertisements.

As time goes by, even when untreated, some of the symptoms of ADHD seen at younger ages tend to dampen, though not disappear, scientists said.

"The frontal lobe of the brain, which controls these behaviors, matures until age 21," Palumbo explained. "As children mature, some symptoms get better though they don't grow out of ADHD, as used to be believed, and half need treatment into adulthood."

Research has shown, in fact, the behavioral shift over the early years can be sufficiently profound to alter an initial diagnosis.

In a study of 118 tots ages 4 to 6, the investigators observed in some cases the symptomatic comportment took so many twists and turns over the eight-year study period, it detoured from the original classification, falling into another category of the disorder or even out of the ADHD realm altogether.

"Was (hyperactivity/impulsivity) 'outgrown,' suggesting that it is only a transient problem that may not require treatment, or did (these) children shift to (another ADHD category)?" the study authors wondered. Their qualified answer: "Both."

FDA Advisory Committee Recommends 'Black Box' Warning for Ritalin, Adderall, Concerta, and Other ADHD Drugs for Potential Risk of Heart Attacks, Strokes, and Sudden Death

Fri, 10 Feb 2006 00:00:00 -0800

In what many experts are viewing as an unusual turn of events, an FDA advisory panel has voted to recommend that the agency order the inclusion of the most serious “black box” warning on all stimulant ADHD medications due to evidence of a potential risk of heart attacks, strokes, and sudden death. The drugs include amphetamines, such as Adderall, and methylphenidates, sold as Ritalin, Concerta, Methylin, and Metadate.

What makes this action (by an 8-7-1) vote surprising to critics of what they see as an influence-riddled agency beholden to the pharmaceutical industry and a system that “rubber stamps” the fully-expected recommendations of supposedly independent panels is that the FDA is now faced with a vote that is clearly against the best interests of the drug companies.

Thus, rather than having a “safe” vote that the agency can simply endorse as its position on a drug, the FDA is already expressing its view of the vote in terms that strongly suggest it may not adopt the panel’s carefully considered recommendation. This has done little more than throw fuel on an already blazing fire.

The panel also voted 15-0-1 to recommend that the FDA require that the drugs include a medication guide for patients and parents. All of this controversy was prompted by data that showed that widely prescribed ADHD drugs like Ritalin may be lined to as many as 25 deaths that occurred between 1999 and 2003. Of these deaths, 19 involved children. In addition, the FDA was advised of 54 cases involving serious cardiovascular problems like heart attacks, strokes, hypertension, heart palpitations and arrhythmias in both adults and children taking these medications.

There is also the open issue of another 26 deaths between 1969 and 2003 in medicated ADHD patients involving suicide, intentional overdose, drowning, heat stroke, and underlying diseases.

The panel’s vote also caught the FDA off guard because the committee was convened to advise the agency on how to design studies to assess possible risks associated with stimulant ADHD medications.

During the meeting, however, talk soon turned to the over-prescribing of these drugs and the public as well as many doctors were unaware of these serious potential risks. The panel then agreed to consider the enhanced-warning issue that was outside of its planned agenda.

In attempting to lay the foundation for ignoring the panel’s vote, officials said they would be reluctant to require a black box warning based on a “theoretical risk.”

Such warnings could unreasonably deter patients and doctors from using a drug that could benefit them, said Robert Temple, MD, director of medical policy at the FDA's Center for Drug Evaluation and Research. He stated: "The absence of bona fide problems in your hand pushes against the box. We will also, frankly, worry about the possibility that overstatement can do active harm."

Thus, Temple indicated the full FDA would wait for the recommendation a pediatric advisory committee scheduled for March before reaching any decision with respect to new warnings. That panel, which is made up of pediatricians and psychiatrists, is considered more likely to look favorably on the benefits of ADHD drug treatment as outweighing the potential risks.

ADHD pills need warning, panel says

Fri, 10 Feb 2006 00:00:00 -0800

A Food and Drug Administration advisory panel Thursday urged that the strongest-possible safety warning be issued for drugs used by millions of children and adults to treat attention-deficit hyperactivity disorder because of emerging concern that they may increase the risks of heart attacks, strokes and sudden death.

The FDA had called the drug-safety experts together to help design further research into such risks. But in an unexpected twist, a majority of the panel members concluded the evidence of serious risks was so great that a strong new warning not just more research was needed.

"This is out-of-control use of drugs that have profound cardiovascular consequences," said Dr. Steven Nissen, a Cleveland Clinic cardiologist and member of the panel.

Although ADHD is commonly associated with children, members of the safety panel emphasized that the drugs could pose a greater danger to adults.

The FDA has received reports of several dozen deaths linked to the drugs, and a larger number of cases involving serious health consequences, such as heart attacks.

The safety panel voted 8-7 to call for a "black box" warning on literature distributed with the drugs, which include well-known brands such as Ritalin, Adderall and Concerta.

As many as 4 million Americans take the medications, and government figures show that almost 10 percent of all 10-year-old boys in the United States get the drugs; only about 4 percent of girls that age use them.

The safety experts also voted unanimously to recommend that a brochure be provided to patients and families to inform them in greater detail about the risks and benefits of using the drugs. And it urged the FDA to expedite studies to better understand the drugs' effects.

Senior FDA officials said they would study the panel's recommendations and that they planned to refer the issue to another advisory panel dealing with psychological problems in children. The agency has been criticized in the past for being slow to respond to evidence of health risks associated with drugs, including painkillers and anti-depressants.

"You don't want to over-scare people and make them not use an important drug," said Dr. Robert Temple, a top policy official at the FDA. "But you don't want people using drugs if they don't have to."

Drug makers said Thursday that the attention-deficit medications are safe when taken as directed. They noted that some have been in use for more than 50 years.

Shire, the maker of Adderall, said it would work with the FDA to make sure patients have all the information they need, but that stronger warnings are not needed. Novartis, which makes Ritalin, said it has reviewed its own data and has not seen any increase in heart risks for patients.

The companies suggested there probably were other explanations for the deaths and serious health issues reported to the FDA, such as heart problems that had gone undetected before the patient was taking the medication.

Most of the attention-deficit drugs are derived from powerful stimulants, including amphetamines. They are thought to help patients concentrate, though exactly how they work is not clear. But they also raise blood pressure, a major risk factor for heart disease and stroke.

Attention-deficit hyperactivity disorder can make it difficult for children to apply themselves in school; adult patients may have trouble with multitasking. In the United States, an estimated 2.5 million children and 1.5 million adults are taking medication for the condition.

Though the drugs have been widely used by children since the 1990s, their use to treat adults is relatively new. Prescriptions written for adults increased by 90 percent from 2002 to 2005. And the risks for adults may be greater, because high blood pressure and heart conditions are more prevalent among adults.

Currently, 10 percent of those taking ADHD drugs are 50 or older.

FDA officials convened Thursday's meeting after they began to worry that the drugs could be present problems.

"We wouldn't be going through this exercise if we didn't think there was a real possibility of an increase in risk," said Dr. David Graham, the FDA drug-safety investigator who was one of the first to call attention to the heart risks of Vioxx, a leading painkiller withdrawn from the market in 2004.

The risks appear to be different for children and adults. Graham and his colleagues undertook a preliminary study using information in the databases of large health insurers and government programs. Their early findings indicated a higher-than-expected number of heart attacks and strokes among adults taking the medications.

Among children and teens through age 18, the number of strokes was higher than expected but the number of heart attacks was lower.

Not all ADHD drugs are the same. One medication, Strattera, is not classified as a stimulant. But several panel members said the warnings should apply to the entire class of drugs, without exception. That may put a brake on overprescribing, they said.

The FDA's Temple said that agency officials would discuss internally how to address the problem of the emerging risk for adults.

The panel members suggested several types of studies to look at safety issues for all patients.

The studies could take two years or more to complete.

Canada halted sales of Adderall last year after health authorities there received 20 reports of sudden deaths in patients. But the drug was allowed back on the market after statistical studies indicated it was no riskier than other medications.

It is not recommended for patients with underlying heart problems, however.

'Black box' label urged after deaths of some on Ritalin, other drugs

Feds Consider Warnings on ADHD Drugs

Thu, 09 Feb 2006 00:00:00 -0800

Federal health advisers considered on Thursday whether warning labels might be needed on drugs for attention deficit hyperactivity disorder following the deaths of 25 people taking the increasingly popular medicines.

Analysis of reports of death and injury suggests a possible link between the drugs and cardiovascular problems, said Dr. Kate Gelperin of the Food and Drug Administration. But she told an FDA advisory panel that the link is not conclusive, nor is it clear whether there is an increased incidence of death or serious injury among people treated with the drugs.

That, Gelperin said, "is really a question we'd like to have answered."

The deaths occurred between 1999 and 2003, according to FDA staff. Nineteen involved children. The report also detailed 54 cases of serious cardiovascular problems, including heart attack, stroke, hypertension, palpitations and arrhythmia, in adults and children being treated with ADHD drugs.

Some of these ADHD drug-treated patients had pre-existing heart conditions or hypertension. That could lead to a new warning on the labels on the drugs, the FDA said.

The drugs include amphetamines, such as Adderall, and methylphenidates, sold as Ritalin, Concerta, Methylin and Metadate.

The FDA said it has tallied an additional 26 deaths between 1969 and 2003 in ADHD patients involving death by suicide, intentional overdose, drowning, heat stroke and from underlying disease.

The FDA's Drug Safety and Risk Management advisory committee is considering how best to study whether the deaths and injuries are linked to use of the drugs, as well as specific ways of conducting such studies. The few studies that have looked at longer-term use of ADHD drugs provide little information on those risks, the FDA said.

Sen. Chuck Grassley, R-Iowa, criticized the FDA's pace in studying the issue earlier this week.

In a letter sent Monday to acting FDA commissioner Dr. Andrew von Eschenbach, Grassley said in part, "I remain concerned that while both psychiatric and cardiovascular risk signals have cropped up across this class of drugs this past year, it appears that FDA is just now beginning to 'discuss approaches' for studying these risks."

An FDA review found fewer than one case of death or serious injury per 1 million ADHD drug prescriptions filled, with one exception: 1.79 cases per million of nonfatal cardiovascular or cerebrovascular problems in adults treated with amphetamines.

Currently, about two million children and one million adults are prescribed ADHD drugs each month, the FDA's Dr. Andrew Mosholder said. Adult use alone grew 90 percent between March 2002 and June 2005, he said.

Sales of ADHD drugs increased to $3.1 billion in 2004, from $759 million in 2000, according to IMS Health, a pharmaceutical information and consulting firm.

The FDA's Canadian equivalent, Health Canada, briefly pulled the ADHD drug Adderall XR from the market last year. A Canadian panel eventually concluded there was inadequate evidence of increased harm from the drug. The FDA reached a similar conclusion at the time.

Adderall is made by Shire Pharmaceuticals and Ritalin is made by Novartis Pharmaceuticals Corp. Various other companies make generic versions of Ritalin as well.

Feds Recommend Warnings on ADHD Drugs

Thu, 09 Feb 2006 00:00:00 -0800

Federal science advisers voted narrowly Thursday to recommend the most serious type of warning labels for Ritalin and other stimulants that are used to treat attention deficit hyperactivity disorder.

The 8-7 vote, with one abstention, by the Food and Drug Administration committee was to recommend adding "black box" safety warnings to ADHD drugs. Doctors prescribe the increasingly popular drugs to about 2 million children and 1 million adults a month.

The FDA isn't required to follow the recommendations of its advisory committees but typically does.

The federal agency originally had asked the scientific panel to consider ways of studying the drugs, which include amphetamines, such as Adderall, and methylphenidates, sold as Ritalin, Concerta, Methylin and Metadate.

The agency's own data suggested a link between the drugs and an increased risk of sudden death and serious cardiovascular problems, including heart attacks.

The panel quickly turned to a debate on whether it should consider new warnings for the drugs rather than simply discuss the need for more studies.

Panel member Dr. Curt Furberg said it would be "inappropriate, unethical behavior" for the FDA not to disclose to doctors and patients that there was uncertainty about the safety of ADHD drugs.

Dr. Steve Nissen told his colleagues they should push for the black box warning on the drugs' packages.

The drugs already bear warnings related to the possible risk they could pose to patients with heart defects, the FDA's Dr. Gerald DalPan said.

"We feel this warning is appropriate given our current knowledge of these drugs," he said prior to the votes.

The balloting on warning labels followed an earlier 15-0 vote to recommend that the FDA require that the drugs include a medication guide for patients and parents.

A federal health official said Thursday that there was a strong possibility the drugs may be linked to the deaths of 25 people.

"There's smoke. Does that represent a fire?" asked Dr. David Graham of the Food and Drug Administration.

The deaths occurred between 1999 and 2003, according to an FDA report. Nineteen of them involved children. The report also detailed 54 cases of serious cardiovascular problems, including heart attack, stroke, hypertension, palpitations and arrhythmia, in adults and children being treated with ADHD drugs.

Some of these patients had pre-existing heart conditions or hypertension.

The FDA said it has tallied an additional 26 deaths between 1969 and 2003 in ADHD patients involving death by suicide, intentional overdose, drowning, heat stroke and from underlying disease.

The FDA's Drug Safety and Risk Management advisory committee was reviewing different ways to study whether the deaths were linked to use of the drugs. The few studies that have looked at longer-term use of ADHD drugs provide little information on those risks, the FDA said.

Analysis of the reports of death and injury suggests a possible link between the drugs and cardiovascular problems, the FDA's Dr. Kate Gelperin told the panel. But the link is not conclusive, nor is it clear whether there is an increased incidence of death or serious injury, she said.

That, Gelperin said, "is really a question we'd like to have answered."

An FDA review found fewer than one death or serious injury per 1 million ADHD drug prescriptions filled, with one exception: 1.79 cases per million of nonfatal cardiovascular or cerebrovascular problems in adults treated with amphetamines.

Sales of ADHD drugs increased to $3.1 billion in 2004, from $759 million in 2000, according to IMS Health, a pharmaceutical information and consulting firm.

That stepped up use could spell increased risk.

"Because adults have a higher risk of heart disease and stroke to begin with, any increase in risk caused by these drugs could affect a large number of people," Graham said.

The FDA's Canadian equivalent, Health Canada, briefly pulled the ADHD drug Adderall XR from the market last year. A Canadian panel eventually concluded there was inadequate evidence of increased harm from the drug. The FDA reached a similar conclusion at the time.

Adderall is made by Shire Pharmaceuticals and Ritalin is made by Novartis Pharmaceuticals Corp. Various other companies make generic versions of Ritalin as well.

Drug under scrutiny

Thu, 02 Feb 2006 00:00:00 -0800

A hyperactivity drug linked last year to deaths, strokes and heart attacks in dozens of patients is expected to face new scrutiny next week when a government advisory committee considers how to study the safety of such medications.

A Food and Drug Administration advisory committee will meet Feb. 9 and 10 to discuss life-threatening side effects linked to drugs that treat attention deficit hyperactivity disorder (ADHD). Adderall, an ADHD drug made by Shire Plc in England, is expected to be on the agenda.

In 2005, Canada withdrew Adderall XR, an extended release capsule, from the market after it was associated with 20 deaths - 14 in children - and a dozen strokes. The deaths occurred in the United States between 1999 and 2003. Canada later allowed Adderall back on the market.

The FDA did not remove Adderall from drugstores here. However, before the Canadian action, the FDA had required Shire to change its U.S. label for Adderall to include a warning about sudden deaths in children with cardiac abnormalities.

Dr. Peter Gross, chairman of the FDA's Drug Safety and Risk Management Advisory Committee said Tuesday that the panel will contemplate methods for studying the risks posed by ADHD drugs like Adderall while continuing to allow doctors to prescribe them. Gross said Adderall has not come before the committee in the past.

Gross said the committee usually suggests "a risk management plan and the FDA advises us later on what was done with the risk management plan."

In 2005, the FDA also said it had logged seven sudden deaths in children taking two other ADHD drugs, Concerta, marketed by Johnson & Johnson, and Ritalin, made by Switzerland's Novartis. An FDA announcement about next week's meeting did not specify which ADHD drugs will be discussed.

Arthur Levin, another member of the FDA advisory committee and director of the Manhattan-based Center for Medical Consumers, said of Adderall: "It appears as if there's reason for concern but how strong the evidence is is not clear. Obviously, there's not convincing data one way or the other."

Shire spokeswoman Heidi Wunder said the drug company will send representatives to attend the public FDA meeting in Gaithersburg, Md., but that they are not scheduled to speak.

FDA spokeswoman Alice Cohen provided no details except to say that the meeting would address "scientific issues."

The FDA also is expected to update the committee on steps taken to monitor the safety of Accutane, the acne drug, and Cox-2 inhibitors that treat pain resulting from conditions like arthritis or bursitis.

Another FDA panel, the Pediatric Advisory Committee, has scheduled a March 22 meeting to consider side effects connected to Adderall and several other ADHD drugs used by children.

FDA to probe ADHD drug safety

Thu, 05 Jan 2006 00:00:00 -0800

The US Food and Drug Administration is planning to review the cardiovascular risks of attention-deficit hyperactivity disorder treatments, and has asked an advisory panel to discuss the issue at a meeting on February 9-10.

The move follows reports of sudden deaths, strokes, heart attacks and high blood pressure in both children and adults taking drugs to treat ADHD, according to the agency.

Last June, the FDA announced an investigation into the safety of ADHD products based on the stimulant drug methylphenidate, including Johnson & Johnson's once-daily Concerta product, and said it was considering extending the review to include all ADHD treatments on the market. But the agency was subsequently advised to hold back on any label changes until it was established whether the reported side effects were common to all drugs in the class.

"The few controlled clinical studies of longer term drug treatment of ADHD provided little information on cardiovascular risks," said the FDA. The Drug Safety and Risk Management Advisory Committee will be asked to discuss approaches that could be used to study whether these products increase the risk of adverse cardiovascular outcomes.

Use of ADHD drugs is expanding rapidly in the USA, according to a report published last year by pharmacy benefits company Medco. Prescribing swelled 23% among young adults (aged 20-34), with a 40% in the amount spent on these prescriptions, while use older adults also climbed, up 33% in adults aged 39-49 and 36% in those aged 50-64.

FDA to examine new ways to study ADD drugs

Wed, 04 Jan 2006 00:00:00 -0800

Reports of sudden deaths, strokes, heart attacks and hypertension in both children and adults taking drugs to treat attention deficit hyperactivity disorder are spurring new government study into the medications’ safety.

Sales of drugs to treat ADHD have increased sharply in recent years, with use growing at a faster rate among adults than children, according to a recent study by Medco Health Solutions, a prescription benefit manager. Spending on ADHD drugs soared from $759 million in 2000 to $3.1 billion in 2004, according to IMS Health, a pharmaceutical information and consulting firm.

The Food and Drug Administration said it had received reports of what it called “serious adverse events” including deaths in association with the therapeutic use of the drugs. The agency considers the reports “rare though serious,” FDA spokeswoman Susan Bro said Wednesday.

The FDA’s Canadian counterpart, Health Canada, yanked the ADHD drug Adderall XR from the market for six months last year in response to reports of 20 sudden deaths and 12 strokes in adults and children using the drug. A number of the cases involved children with structural heart defects.

The panel eventually concluded there was inadequate evidence of increased harm from Adderall XR compared with other available therapies a conclusion the FDA also reached based on data on hand.

Now the U.S. regulatory agency is asking its Drug Safety and Risk Management advisory committee to examine ways of studying further the potential cardiovascular risks of the drugs. The few studies that have looked at longer-term use of ADHD drugs provide little information on those risks, the FDA said.

“It almost sounds like cox-2 inhibitor redux,” said committee chairman Dr. Peter Gross, referring to cox-2 painkillers like Vioxx and Bextra pulled from the market because of evidence they can raise the risk of a heart attack or stroke.

The committee is to meet Feb. 9 and 10 in Gaithersburg, Md.

“The issue of drug treatment of attention deficit disorder in children has been a controversial one without this issue of cardiovascular risk too. It adds another concern to what will certainly be an interesting conversation,” said Arthur Levin, the FDA committee’s consumer representative.

A posting to the FDA Web site did not identify any of the drugs by name. However, the most commonly used ADHD drugs include Adderall XR, made by Shire Pharmaceuticals, and Ritalin, made by Novartis Pharmaceuticals Corp. Various other companies make generic versions of Ritalin as well.

Shire spokesman Matthew Cabrey said the company hadn’t been told of the meeting but added it may send representatives. Novartis did not immediately return a call seeking comment.

The committee’s Feb. 10 meeting will include updates on FDA actions on cox-2 drugs as well as a recently begun patient, doctor and pharmacist registry program for the anti-acne drug Accutane and its generic competitors.

Separately, the committee also will discuss the FDA’s Drug Safety Oversight Board, an internal, government employee-only panel created nearly a year ago.

The board is supposed to monitor FDA-approved medicines once they’re on the market and update physicians and patients with emerging information on risks and benefits.

Gross said he had concerns about the board’s impartiality and independence, as well as its relationship to his committee and the very similar work it does.

New Warnings Due for ADHD Drugs

Thu, 30 Jun 2005 00:00:00 -0700

The Food and Drug Administration plans to add new warnings about psychiatric side effects to the label of Concerta and other drugs for attention deficits and hyperactivity, according to documents posted on the FDA Web site and confirmed by the agency.

At a meeting today of the FDA's Pediatric Advisory Committee, officials will discuss safety concerns about Concerta, a form of methylphenidate, the active ingredient in Ritalin and similar medications.

A briefing document about the meeting says the review was prompted by reports of hallucinations, suicidal thoughts, psychotic behavior and aggression among methylphenidate users. Officials note that Concerta's label already lists possible psychiatric side effects but suggests the problems aren't serious or that the drug might only aggravate existing problems.

The FDA also has received reports of cardiovascular problems among Concerta users, such as high blood pressure, arrhythmia and racing heartbeats. The agency doesn't yet know whether these problems are caused by the drug.

Attention-deficit hyperactivity disorder (ADHD) affects about 7.5% of school-age children, Concerta's maker says. The drug, approved in 2000, is intended to improve concentration and impulse control. Patients filled 7.8 million prescriptions last year, the FDA report says.

The agency also plans to examine other stimulants used to treat ADHD, including amphetamines and Strattera. Last year, the FDA changed the label for Adderall XR to include risk of sudden cardiovascular death, especially in children with heart disease, the report says.

Bonnie Jacobs of McNeil Consumer & Specialty Pharmaceuticals, a division of Johnson & Johnson that makes Concerta, says the company is reviewing the information and "will of course do what is in the best interest of patients."

ADHD Drug Comes Under Scrutiny From Parents

Tue, 29 Mar 2005 00:00:00 -0800

Parents whose children take Adderall XR for Attention-Deficit Hyperactivity Disorder (ADHD) face a dilemma :whether to let their kids stay on a medicine that could be unsafe when experts say there is a lack of long-term research to guide the decision.

The popular drug, which has been linked to 20 sudden deaths worldwide, mostly in children, has been taken off the Canadian market, sparking questions about whether kids in the United States should be using it.

The Food and Drug Administration issued a public health advisory on its Web site saying that the rate of sudden death for children on Adderall XR is no higher than for those not on the drug. But children with heart defects could be at higher risk.

Parents are making decisions about stimulants such as Adderall XR with few facts, says Julie Magno Zito, an epidemiologist at the University of Maryland. There are no good long-term studies of such medicines, she says. Rare side effects of a drug won't surface in short studies unless they include a huge number of kids, such as in a national HMO, and that kind of study hasn't been done on Adderall XR, Zito says.

About 700,000 children in the United States take Adderall XR, a timed-release stimulant, and 300,000 use Adderall, a version that often needs to be taken more than once a day, according to Shire Pharmaceuticals Group PLC, maker of the drug.

Parents whose kids are doing well on Adderall might consider a "wait and see" approach for now, says Baltimore pediatrician Richard Gorman. "School failure is a big issue for kids with ADHD, and these are very rare effects so far."

Of the 20 reports of sudden death, 12 were in the United States from 1999 to 2003, a time frame when 30 million prescriptions were written for the medicine, according to the FDA advisory.

More deaths could be reported in the wake of Canada's decision to pull the drug off shelves. On the other hand, the withdrawal could be rescinded if harmful effects are confirmed to be rare, Gorman says.

Shire Suspends Sales Amid Safety Fears

Thu, 10 Feb 2005 00:00:00 -0800

Shire Pharmaceuticals saw its share price plunge 10% today after its best-selling drug was ordered off the shelves in Canada amid safety fears.

Canadian health officials demanded the suspension of sales of its Adderall XR hyperactivity treatment after the drug was linked to 20 sudden deaths.

They cited data showed that 14 children and six adults had died after taking the usual recommended doses of the drug, while there were also 12 reports of strokes in patients.

In a statement, regulators said: The incidence of serious adverse reactions leading to death was higher in Adderall and Adderall XR combined than in the other drugs of this class.

Shire said it had agreed to suspend sales of the drug in Canada even though it strongly disagreed with the conclusions of officials at Health Canada.

It was considering appropriate responsive action and said the issue was linked to labelling of the drug, which should stress that it should not be used by children or adults with heart problems.

Adderall XR was approved in Canada in January last year and launched the following month, with around 11,000 patients using it to treat attention deficit hyperactivity disorder in the country currently.

It contributed 10 million US dollars to annual revenues in its first year on the Canadian market. Global sales of Adderall XR account for 43% of the total turnover of the company.

Chief executive Matthew Emmens said: We are surprised by this action from Health Canada. Shire remains confident in the safety and efficacy of Adderall XR.

Labelling of the drug in the United States was revised in September and Shire said the same data had been considered by the Food and Drugs Administration (FDA) there.

Analysts said shares in Shire would have collapsed if investors thought that US regulators were likely to follow their Canadian counterparts in suspending sales of the drug.

Dr Jonathan Senior, of Evolution Securities, said: Unless there is something lurking in the data that the FDA hasnt seen then it is unlikely to lead to a withdrawal in the US, which would be a massive blow to them.

The crisis that followed the withdrawal of the Vioxx painkiller manufactured by rival drugmaker Merck last year meant the FDA was likely to look again at the data, but Dr Senior said this would be to dot the Is and cross the Ts.

Shire, based in Basingstoke, is the UKs third-largest pharmaceuticals group behind GlaxoSmithKline and AstraZeneca. The product is not available in the UK.

Health Canada Orders ADHD Drug Off Market After Reports of Deaths, Strokes

Wed, 09 Feb 2005 00:00:00 -0800

Health Canada has ordered a once-a-day
treatment for attention deficit hyperactivity disorder off the market after learning the drug has been linked to 20 sudden deaths and 12 strokes, including among children.

And makers of related stimulants used to treat the
commonly diagnosed condition have been asked to
provide a thorough review of their worldwide safety data, Health Canada said in a release late Wednesday. None of the deaths or strokes associated with Adderall XR were reported Canada, said department spokesman Ryan Baker.

"However, Health Canada has received eight reports of adverse reactions ranging in severity from convulsions to minor skin rash," Baker said.

"It's not been determined yet whether these reactions were a result of Adderall XR use."

Of the 20 cases of sudden death linked to the drug, 14 were in children. Two of the 12 strokes were suffered by children taking the drug. The adverse reactions were not associated with overdose, misuse or abuse of the drug, the department said.

The drug is made by Shire Biochem Inc. and is sold in Canada and the United States. A related
immediate-release form of the drug, sold simply as
Adderall, is sold in the U.S. but has never been
approved for sale in Canada.

Health Canada is asking people taking the drug or
parents of children on it to consult their physicians immediately to select alternatives. It is also asking them not to flush unused pills down a toilet or sink but rather to take them to a pharmacy for safe
disposal.

People taking related drugs for the management of ADHD should not stop their treatment but could consult their doctors if they have concerns, the department said.

In light of the international reports of adverse
reactions, the department reviewed the drug's safety data and conducted a preliminary review of safety data for the other related stimulants authorized for treatment of ADHD in Canada.

The incidence of serious adverse reactions leading to death was higher in Adderall and Adderall XR combined than in any other drugs of this class, the release
said.

ADHD is the most commonly diagnosed psychiatric
disorder among school-aged children.

PUBLIC ADVISORY - Health Canada Important Safety Information on ADDERALL XR(R)

Wed, 09 Feb 2005 00:00:00 -0800

Health Canada is informing Canadians that
it has instructed Shire BioChem Inc., the manufacturer of ADDERALL XR(R) to withdraw the drug from the Canadian market. Health Canada has suspended the market authorization of the product due to safety information concerning the association of sudden deaths, heart-related deaths, and strokes in children and adults taking usual recommended doses of ADDERALL(R) and ADDERALL XR(R). The immediate release form of ADDERALL(R) has never been marketed in Canada.

Health Canada is advising patients who are currently being treated with ADDERALL XR(R) to consult their physician immediately about use of the drug and selecting treatment alternatives.

Health Canada's decision comes as a result of a thorough review of safety information provided by the manufacturer, which indicated there were 20 international reports of sudden death in patients taking either ADDERALL(R) (sold in the United States, not in Canada) or ADDERALL XR(R) (sold in Canada).

These deaths were not associated with overdose, misuse or abuse. Fourteen deaths occurred in children, and six deaths in adults. There were 12 reports of stroke, two of which occurred in children. None of the reported deaths or strokes occurred in Canada.

A preliminary review of safety data for the other related stimulants authorized for use in the treatment of ADHD in Canada has been conducted. In that review, the incidence of serious adverse reactions leading to death was higher in ADDERALL(R) and ADDERALL RX combined than in the other drugs of this class.

Health Canada has asked manufacturers of other related stimulants approved for the treatment of ADHD to provide a thorough review of their
worldwide safety data. Information updates will be provided by Health Canada as they become available.

Patients taking drugs of the same class for the management of ADHD should NOT discontinue their medication, and should consult with their physician if they have any concerns or questions.

ADDERALL XR(R), a Central Nervous System (CNS) stimulant, was approved in Canada on January 23, 2004 for the management of Attention Deficit Hyperactivity Disorder (ADHD) in children.

After having consulted with their physician, consumers should not flush unused drugs down the toilet or sink to avoid contaminating ground or municipal water systems but return any unused product to their pharmacy.

Health Canada has been in contact with Shire BioChem Inc., and will be monitoring the removal of this product from the Canadian market.

FDA Alert Sudden Death in Children

Wed, 09 Feb 2005 00:00:00 -0800

Health Canada has suspended marketing of Adderall XR (extended release) from the Canadian market due to concern about reports of sudden unexplained death (SUD) in children taking Adderall and Adderall XR. SUD has been associated with amphetamine abuse and reported in children with underlying cardiac abnormalities taking recommended doses of amphetamines, including Adderall and Adderall XR. In addition, a very small number of cases of SUD have been reported in children without structural cardiac abnormalities taking Adderall. At this time, FDA cannot conclude that recommended doses of Adderall can cause SUD, but is continuing to carefully evaluate these data.

Recommendations

FDA is currently examining the data on these cases occurring in children who are using Adderall as recommended. As a precaution, FDA recommends that Adderall products not be used in children or adults with structural cardiac abnormalities.

Data Summary

A review of the data from the FDA's Adverse Event Reporting System database for the years 1999 through 2003 identified 12 cases of sudden death in pediatric patients (1 to 18 years of age) who were being treated for ADHD with Adderall or Adderall XR (see table for description of cases).

Characteristics of domestic pediatric sudden death cases reported during past five years (n=12)*

Age: 7-16 years (mean 12. years)

Gender: 12 male, 0 female

Suspect drug: Adderall or Adderall XR

Total daily dose: 10 mg (1), 20 mg (5), 30 mg (1), 40 mg (1), 50 mg (1) , NR (3)

Duration of therapy: 1 day 8 years (range)

Autopsy: yes (11), not mentioned or not done (1)

Cardiac structural abnormalities: aberrant origin of coronary artery (1), idiopathic hypertrophic subaortic stenosis (1), bicuspid aortic valve (1), cardiac hypertrophy (2)

Other risk factors: unexplained increase or toxic amphetamine level (2), family history of ventricular arrhythmia (1), extreme exercise and dehydration (1)

Concomitant meds: none mentioned (9), 1 med (3)

Year reported: 1999 (0), 2000 (2), 2001 (6), 2002 (2), 2003 (2)

*numbers in parentheses represent count of cases

Five of the 12 pediatric sudden death cases described cardiac risk factors including undiagnosed cardiac abnormalities (e.g., aberrant origin of coronary artery, bicuspid aortic valve, idiopathic hypertrophic subaortic stenosis). Seven occurred in children without such abnormalities, including 1 with a positive family history of ventricular arrhythmia. Several of the cases were complicated by other illness, and very rigorous exercise. Unusual and unexplained accumulation of drug resulting in toxic levels during usual therapeutic dosing also appears to have played a role in several of the pediatric sudden death cases. The rare occurrence of sudden death during stimulant therapy of ADHD deserves continued evaluation.

SUD as a possible effect of amphetamines should be considered in the assessment of benefit versus risk during therapeutic decision-making for individual patients. In the pediatric population, potential risk factors include cardiac abnormalities that may be undiagnosed, positive family history for ventricular arrhythmias, and as yet unidentified factors that may cause excessive levels of stimulant to accumulate in children who are taking apparently normal doses.

Health Canada Has Suspended Market Authorization of ADDERALL XRTM (amphetamine salts), A Drug Approved for Attention Deficit Hyperactivity Disorder (ADHD) In Children

Wed, 09 Feb 2005 00:00:00 -0800

Health Canada advises you that marketing of the Attention Deficit Hyperactivity Disorder (ADHD) drug, ADDERALL XRTM (amphetamine salts) has been suspended effective February 9, 2005. ADDERALL XRTM, marketed by Shire BioChem Inc., is a prescription drug that was authorized in Canada for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children.

Health Canada's decision to withdraw ADDERALL XRTM is founded on very rare, international, spontaneous reports of sudden deaths, in paediatric and adult patients in association with ADDERALL (immediate release) and ADDERALL XRTM (extended release). Reports for death include those for patients taking usual recommended doses, including recommended starting doses, of ADDERALL and ADDERALL XRTM. In a minority of cases, the events occurred on the first day of dosing or shortly after an increase in dose or a switch from another drug in the structural class. Deaths were reported for patients both nave or chronically exposed to amphetamine-related Central Nervous System stimulants. This decision was not based on reported deaths that were associated with overdose, misuse or abuse. Of the 20 reported deaths, there were cases that occurred in patients without a documented history of structural or other cardiac abnormalities/disease. In a few cases, other drugs, including anti-depressants, clonidine and/or anti-psychotics, were concomitant medications. Exercise was an associated event in some of the reports of death. None of the reported deaths occurred in Canada.

Health Canada is aware of 20 international reports of sudden death in patients taking either ADDERALL (immediate release) or ADDERALL XRTM (extended release) with 3.45 million patient-years of exposure. 14 deaths occurred in children, and 6 deaths in adults. ADDERALL XRTM has been marketed in Canada since January 23, 2004, while the immediate release form of ADDERALL has never been marketed in Canada.

A preliminary review of safety data for the other stimulants authorized for use in the treatment of ADHD in Canada has been conducted. The incidence of serious adverse reactions leading to death was higher in ADDERALL/ADDERALL XRTM than in the other stimulants, based upon these reviews. In addition, the safety information submitted to Health Canada also included 12 reported cases of stroke, with 2 occurring in children.

Health Canada has requested manufacturers of other stimulants approved for the treatment of ADHD provide a thorough review of their worldwide safety data. Information updates will be provided as they become available.

Adderall Stroke Sudden Death Injury Attorney

Wed, 09 Feb 2005 00:00:00 -0800

DOWNLOAD OUR ADDERALL INFORMATION PACKAGE

Injured by Adderall?

The FDA awarded Shire Pharmaceuticals approval for Adderall on November 8, 2002. Adderall is used by approximately 700,000 Americans and is one of the most popular drugs for people with attention deficit hyperactivity disorder. Adderall contains amphetamine and dextroamphetamine, which are both stimulants. Shire Pharmaceuticals Group PLC sold $759 million of Adderall XR in the U.S. and roughly $10 million in Canada in 2004.

Adderall is approved in the United States for the treatment of adults and pediatric patients 6 years of age and older with ADHD, and Adderall, the immediate-release formulation of the drug, is approved for pediatric patients with ADHD. The Food and Drug Administration (FDA) has been aware of these post-marketing cases, and evaluated the risk of sudden death with Adderall prior to approving the drug for treatment of ADHD in adults last year.

On February 9, 2005, Health Canada, the Canadian drug regulatory agency, suspended sales of Adderall in Canada. Adderall is a controlled release amphetamine used to treat patients with Attention Deficit Hyperactivity Disorder (ADHD). The Canadian action was based on U.S. post-marketing reports of sudden deaths in pediatric patients.

In a one-page letter to Adderall's manufacturer, Health Canada, the Canadian regulatory agency, said the "identified risk of sudden death following the recommended doses cannot be managed by label changes." The company said there have been 20 reports of sudden deaths on Adderall's extended release and a prior formulation of the medicine since 1994, when the drug first came on the market.

In a news release, Health Canada said, "the incidence of serious adverse reactions leading to death was higher in" the extended release and earlier formulations of Adderall, when added together, than in other drugs in the same class. Of the 20 deaths reported in patients taking Adderall, 12 were from strokes, and two were in children, Health Canada said.

The FDA is continuing to evaluate these and other post-marketing reports of serious adverse events in children, adolescents, and adults being treated with Adderall and related products.

In August 2005, Health Canada allowed Shire Pharmaceuticals to begin selling Adderall again.

On January 3, 2006, the Food and Drug Administration asked its standing committee of risk-management advisers to review reports of heart-related complications in children and adults using attention deficit disorder drugs. U.S. and Canadian regulators have been looking in the past few years at the probable heart risk of attention-deficit drugs, which are stimulants used to improve concentration.

The three main ADHD drugs that will be reviewed at the February 9, 2006 FDA review meeting include Adderall, Concerta, and Strattera.

On February 9, 2006, Federal science advisers voted narrowly on proposing the most serious type of warning labels for Adderall, Concerta, Ritalin and all other ADHD drugs. The Food & Drug Administration (FDA) Committee voted 8-7, recommending the adding of “black box” safety warnings to ADHD drugs. Doctors prescribe ADHD drugs to approximately 2 million children and 1 million adults a month.

The FDA’s data suggested a link between ADHD drugs and an increased risk of sudden death and serious cardiovascular problems, including heart attacks. Dr. Steve Nissen told his colleagues they should push for the black box warning on the ADHD drugs' packages. A federal health official said Thursday that there was a strong possibility the drugs may be linked to the deaths of 25 people.

The deaths took place between 1999 and 2003, based upon a FDA report. Nineteen of them involved children. The report also detailed 54 cases of severe cardiovascular problems, including heart attack, stroke, hypertension, palpitations and arrhythmia, in adults and children being treated with ADHD drugs.

Sales of Adderall, Concerta, Ritalin and other ADHD drugs increased to $3.1 billion in 2004, from $759 million in 2000, according to IMS Health, a pharmaceutical information and consulting firm.

If you or a loved one took Adderall and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.