Medication Information

Medication News

Press Release

American Academy of Pediatrics (AAP)

RELEASES NEW GUIDELINES FOR DIAGNOSIS OF ADHD

Below is a news release of a policy published in the May issue of Pediatrics, the peer-reviewed scientific journal of the American Academy of Pediatrics (AAP).

For Release: May 1, 2000, 5:00 p.m. (ET)

CHICAGO - The American Academy of Pediatrics (AAP) released new recommendations today for the assessment of school-age children with attention-deficit/hyperactivity disorder (ADHD).

Research in various community and practice settings shows that between 4 and 12 percent of all school-age children may have ADHD, making it the most common childhood neurobehavioral disorder. Children with ADHD may experience significant functional problems such as school difficulties, academic underachievement, troublesome relationships with family members and peers, and behavioral problems.

In recent years, there has been growing interest in ADHD as well as concerns about possible over diagnosis. In surveys among pediatricians and family physicians across the country, wide variations were found in diagnostic criteria and treatment methods for ADHD.

The new standardized AAP guidelines were developed by a panel of medical, mental health and educational experts. The Agency for Healthcare Research and Quality provided significant research and background information for the new policy.

The new guidelines, designed for primary care physicians diagnosing ADHD in children age 6 to 12, include the following recommendations:

ADHD evaluations should be initiated by the primary care clinician for children who show signs of school difficulties, academic underachievement, troublesome relationships with teachers, family members and peers, and other behavioral problems. Questions to parents, either directly or through a pre-visit questionnaire, regarding school and behavioral issues may help alert physicians to possible ADHD.
In diagnosing ADHD, physicians should use DSM-IV criteria developed by the American Psychiatric Association. These guidelines require that ADHD symptoms be present in two or more of a child's settings, and that the symptoms adversely affect the child's academic or social functioning for at least six months.
The assessment of ADHD should include information obtained directly from parents or caregivers, as well as a classroom teacher or other school professional, regarding the core symptoms of ADHD in various settings, the age of onset, duration of symptoms and degree of functional impairment.
Evaluation of a child with ADHD should also include assessment for co-existing conditions: learning and language problems, aggression, disruptive behavior, depression or anxiety. As many as one-third of children diagnosed with ADHD also have a co-existing condition.

Other diagnostic tests, sometimes considered positive indicators for ADHD, have been reviewed and considered not effective. These tests include lead screening, tests for generalized resistance to thyroid hormone, and brain image studies.

Comprehensive ADHD treatment guidelines are also in development.

The American Academy of Pediatrics is an organization of 55,000 primary care pediatricians, pediatric medical subspecialists and pediatric surgical specialists dedicated to the health, safety and well-being of infants, children, adolescents and young adults.

******************************************************************

Warnings About Ephedra
"Natural" does NOT necessarily mean "Safe."

From Bob Seay at About.com

The New England Journal of Medicine has published a report titled "Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids". The report was released to the public on 6 November 2000, almost two months ahead of the planned date of publication. According to editors of the Journal, this was done "because of its potential public health implications." The final version of the report will be published on December 21, 2000.

Ephedra, also known as the herb Ma Huang, is marketed as an aid for weight loss. Because Ephedra is a stimulant, it has also been promoted as a "natural alternative" for treatment of ADHD. Anti-medication groups often mix advocacy with business as they sell and promote products containing the herbal alternative to Ritalin. In April, 2000, concerns about safety prompted the FDA to consider regulation.

How serious is it?
During the study reported in the New England Journal, researchers looked at 140 reports received by the FDA. Of those 140 reports, 31% (43 people) "definitely" or "probably" suffered an adverse effect fromEephedra. Of the 43, seven suffered permanent injury and four more required ongoing medical treatment.

Three people, or just over 2% of cases that reported an adverse reaction, died after using products containing Ephedra. Other serious effects among those people included five cardiac arrests resulting in either permanent brain damage or death, four strokes and 10 cases of hypertension.

Nutritional supplements often escape FDA regulation because they are sold as food and not drugs. The fact that the FDA is actively pursuing this is a good indication of the potential seriousness of the problem. Alternative products for ADHD have been investigated or even shut down by the U.S. Government before. However, the reason is usually related to false or misleading sales campaigns.

Alternative Treatments for ADHD may offer some promise for people with ADHD in some cases. Unfortunately for those who are taking Ephedra, the risks may outweigh any potential benefits.

NEWS FLASH - October 26, 2000

New Non-Stimulant ADHD Medication Shows Promise
Eli Lilly & Co. on October 26, 2000 reported positive results for early clinical testing of tomoxetine, a possible non-stimulant medication for ADHD. The story also appeared as a Reuters news article today.

Tomoxetine is a noradrenergic compound that appears to have less cardiac effect than traditional stimulant medications like Ritalin or Adderall. (Noradrenergic means that it behaves like a stimulant in the body even though it is not an actual stimulant.)

If approved, the medication should be available to the public by 2003 or 2004.

Pharmaceutical Companies Nudged by the DEA
Concern from the Drug Enforcement Agency about Diversion, Trafficking, and Abuse of Methylphenidate (generic Ritalin) has prompted interest in the development of non-stimulant treatments for ADHD. Ritalin, Adderall and Dexedrine are all Schedule II medications. Patients are required to visit the doctor each time a prescription needs to be refilled. CHADD and other ADHD groups had lobbied DEA for a reclassification of Ritalin, citing the needs of parents to be able to more easily obtain refills for their children, but the medication remains on the Schedule II list.

Other concerns about Ritalin include side effects such as headache and loss of appetite, both of which are associated with stimulant medications.

******************************************************************

*****************************************************************8

News Flash: The Relationship Between Medication Treatment for ADHD and Substance Abuse
Stimulants Reduce Likelihood of Later Substance Use a new study says that boys treated with Ritalin or other stimulants are less likely to abuse alcohol and other drugs when they are older, according to an Aug. 2 press release from the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH).

An ongoing source of concern for many parents and clinicians about the use of stimulant medication for treating children with ADHD is that it will increase the risk that these youth will develop SUDs (i.e. substance use disorders) later in life. Given the documented potential for abuse of stimulant medications, and the widespread use of this form of treatment, such concerns are understandable.

A recently published study, however, provides the most compelling data to date on this important issue (Biederman et al.; (1999). Pharmacotherapy of ADHD reduces the risk for substance use disorder. Pediatrics, 104, p. e20.). Although the title of this paper makes the authors' conclusion pretty clear, these are very important data and warrant a careful look.

What were the rates of different types of SUDs in these 3 groups? The data are presented below with the entries indicating the % of teens in each group with the particular SUD.

	Medicated	No Medication	Control
Alcohol	25%	75%	18%
Marijuana	16%	68%	15%
Stimulants	2%	5%	0
Cocaine	2%	16%	1%
Tobacco	34%	32%	16%

As is clearly evident in the figures above, children with ADHD who had not been treated with medication had higher rates of substance use problems than those who had been treated. Rates of substance use for children who had received medication treatment was not appreciably different from control subjects (i.e. marijuana, stimulants, and cocaine).

****************************************************

*****************************************************

Concerta

Safety and Efficacy Data of Once-Daily Concerta (methylphenidate HCl) extended-release tablets (CII) Presented at Pediatric Academic Societies/American Academy of Pediatrics Meeting

Unique Delivery Profile of Concerta™ extended-release tablets (CII) Yields Similar Efficacy to MPH TID with Consistent Improvement in Symptoms Throughout the Day

BOSTON, Mass., May 12, 2000 … ALZA Corporation (NYSE: AZA) today announced the presentation of clinical results of Concerta™ (methylphenidate HCl) extended-release tablets (CII) in the treatment of children with Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (ADD/ADHD). Researchers from the University of California at Irvine presented results today of a study that demonstrated once-daily Concerta™ is superior to placebo and similar in efficacy to methylphenidate given three times a day for the treatment of ADHD. These results were presented at the first joint meeting of the Pediatric Academic Societies and the American Academy of Pediatrics in Boston, Massachusetts.

Concerta™, which is being developed by ALZA on behalf of Crescendo Pharmaceuticals Corporation (Nasdaq: CNDO), is currently under review for marketing approval by the U.S. Food and Drug Administration (FDA) as a once-daily treatment for ADD/ADHD. Concerta™ utilizes ALZA's OROS^® osmotic controlled-release technology to deliver methylphenidate throughout the school day, eliminating the need for in-school and after-school dosing.

"This study demonstrated that Concerta™ taken once-a-day provided consistent improvement in the symptoms of ADHD from the morning through the early evening, and was similar in effectiveness to methylphenidate taken three times a day every four hours," said James Swanson, Ph.D., Director of the Childhood Development Center and Professor of pediatrics and Cognitive Sciences at University of California at Irvine, and lead investigator for the study. "For children diagnosed with ADHD, multiple daily doses of methylphenidate is inconvenient. Concerta™ may help improve compliance because it is taken once a day."

Concerta™ has a uniquely patterned plasma profile that minimizes the peak-trough fluctuations associated with methylphenidate given three times a day. This delivery pattern is designed to extend the duration of effect, provide consistent improvement in symptoms and overcome the need for repeated administration throughout the day. In a previous study, blood levels of medication were assessed throughout the day once a week. "We saw smooth plasma concentrations with Concerta™ without the peaks and valleys in blood levels seen in MPH given three times a day," said Dr. Swanson.

The double-blind, randomized placebo-and active-controlled crossover study evaluated 64 children, aged six to 12 years old with a confirmed diagnosis of ADHD who were currently being treated with methylphenidate. Children received each of three treatments (Concerta™ once a day, MPH three times a day or placebo) for seven days. Over the three-week period, patients were observed in their usual community school five days a week and in a laboratory school setting one day a week. Efficacy was evaluated in multiple settings including community and laboratory schools by both teachers and parents using standardized tests including Inattention/Overactivity with Aggression (IOWA) Conners Inattention/Overactivity (I/O) subscale, which was the primary outcome measure.

The sum of the five IOWA Conners I/O subscale items range from 0 to15, with higher ratings reflecting higher degrees of inattention and overactivity. The IOWA Conners I/O subscale scores from the community school teachers showed a significant improvement for Concerta™ (6.54) and MPH tid (6.89) compared to placebo (11.6), but no significant difference between the two active treatments. Laboratory school teachers used the SKAMP rating scale to measure eight attention items and five behavior items scores nine times throughout the day. SKAMP scores revealed that the onset of action and duration of efficacy were comparable for Concerta™ and MPH tid. In addition, parents showed a preference for Concerta™ over the other treatments in the study and over therapy received prior to the study. The study design ensured that all patients received treatment three times a day for all treatment sequences. Thus, these results do not reflect preferences that may result from different daily dosing schedules. "We surmise parents preferred Concerta™ based on the extent of symptom improvement versus the other treatments," remarked Dr. Swanson.

In the study, Concerta™ was well tolerated and had a similar safety profile to methylphenidate dosed three times daily. Adverse events that occurred in more than 2 percent of patients include headache (4.8 percent), abdominal pain (4.8 percent) and fever (4.8 percent).

*****************************************************************************************************************************

News Flash: New Drug for ADHD

July 20, 1999

The Eli Lilly pharmaceutical company is now in Phase II with pediatric patient studies using a nonstimulant norepinephrine enhancer called Tomoxetine. This very promising medication follows an adult study that demonstrated statistically superior performance in reducint the severity of ADHD symptons. Results of the adult study were published in the American Journal of Psychiarty in May 1998. It is the first time that this type of medication has been studied for ADHD relief. The potential elimination of the side effects from psychostimulants (insomnia and decreased appetite, which result in non-compliance or limited efficacy) is very promising.

We will bring you updates on this new medication as we receive information.

***************************************************************

New Flash: Cylert

The FDA has issued new warnings about the medication Cylert (pemoline). Abbot Laboratories has also issued a statement regarding the deaths due to liver toxicity that have been connected to the drug.

June 21, 1999

Alert - Labeling for Pemoline revised

Abbott Laboratories has issued a Dear Health Care Professional letter in the U.S. announcing labeling changes for pemoline (Cylert). Pemoline is a central nervous stimulant utilized in attention deficit hyperactivity disorder. According to the letter, 15 cases of acute liver failure have been reported in association with the use of pemoline as of December 1998, of which 12 resulted in deaths or liver transplantation.

Apart from the more frequent recommendations for liver function test monitoring, the new label emphasizes that written informed consent should be obtained. Pemoline was withdrawn from the U.K. nearly two years ago. The FDA has posted a copy of the Patient Information/Consent Form and the revised Production Information (labeling) for pemoline.

*****************************************************************************************

******************************************************************************************

News Flash: Ritalin

By Stephanie O'Brien, CBS MarketWatch

WARREN, N.J. (CBS.MW) -- Biotech company Celgene Corp. said it won a key patent that could block rivals from developing a similar version of its attention deficit disorder drug.

The company said the patent covers methods of treatment for attention deficit disorder and attention hyperactivity disorder with Celgene's improved version of Ritalin, themarket leader, which is made by Novartis AG.

Celgene is developing a version of Ritalin that could require a lower dose and have fewer side effects.

The company is beginning Phase III trials of the drug and expects to complete them by the end of this year, John Jackson, Celgene's chief executive, told CBS MarketWatch.

Jackson said he expects Celgene to file in mid-2000 for U.S. Food & Drug Administration approval to market the drug.

"They're building substantial intellectual property protection surrounding this product,"said Maureen McEnroe, an analyst at HCFB/Brenner Securities.

"Ultimately, it could mean that it prevents competitors from developing any other version of existing products if the patent is upheld," McEnroe said. Warren, New Jersey-based Celgene's strategy is similar to that pioneered by Sepracor, which develops and brings to market improved chemical entities that are new, patented forms of existing pharmaceuticals.

The products can offer reduced side effects, improved safety, new uses, and improved dosage forms over traditional compounds. Attention deficit disorder is a problem related to brain development that causes hyperactivity, impulsive behavior and attention problems, according to InteliHealth, the online information service of the Johns Hopkins University

Celgene estimates that about 1 million children in the U.S. have the disorder. That number may be underreported, the company said.

*****************************************************************************************
*****************************************************************************************

News Flash: Ritalin

Stimulants Reduce Likelihood of Later Substance Use a new study says that boys treated with Ritalin or other stimulants are less likely to abuse alcohol and other drugs when they are older, according to an Aug. 2 press release from the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH).

Ritalin and other stimulants are used to treat attention deficit hyperactivity disorder (ADHD). The study compared three groups of boys: those with ADHD who had been treated with stimulants; those with ADHD but not treated with stimulants; and those without ADHD.

The intent of the study was to determine the boys' susceptibility to substance abuse. Researchers at Massachusetts General Hospital, the Harvard School of Public Health and Harvard Medical School found that 75 percent of the ADHD boys receiving no treatment had at least one substance use disorder, compared to 25 percent of the medicated ADHD boys, and 18 percent of the boys without ADHD.

"While some clinicians have expressed concern about giving stimulants to children with ADHD because they fear it might increase the risk that these children will abuse stimulants and other drugs when they get older, this study shows exactly the opposite," said NIDA Director Alan I. Leshner. "Treating the underlying disorder, even if with stimulants, significantly reduces the probability they will use drugs later on."

The study is published in the Aug. 2 issue of Pediatrics.

Information provided by David Rabiner, Ph.D. in his ADHD Research Preview Issue.