Category — ADHD: Adderall

WSJ Article Excerpts:

By ANNA WILDE MATHEWS
Staff Reporter of THE WALL STREET JOURNAL
August 24, 2005; Page A1

DOWNEY, Calif. – When Eli Lilly & Co. wanted to get the big California health-maintenance organization Kaiser Permanente to use its new antidepressant, it ran straight into Debbie Kubota.

As the cost of drugs in the U.S. approaches $250 billion a year, pharmaceutical companies are running up against a growing breed of detective trained to see through marketing spin. Working for insurers, state Medicaid programs and nonprofit bodies, these detectives cast a wary eye on published studies in medical journals, once considered an unimpeachable source. They search for subtle aspects of clinical-trial design that might show the drugs are not all they’re cracked up to be.

“You could be duped,” says Siri Childs, who oversees pharmacy policy for the Washington state Medicaid program. “We know now that just because it’s published in a medical journal, that doesn’t assure its quality.”

The Cochrane Collaboration, a nonprofit that analyzes the quality of studies and collects the ones it considers good into broader analyses, has a volunteer corps of about 7,500 reviewers, mostly doctors and academics. That’s up from about 2,800 five years ago. Another player is the Drug Effectiveness Review Project, an effort by an Oregon nonprofit. It issues reports summarizing all the studies in a particular treatment area and often criticizes individual studies for failings such as inadequate controls and high dropout rates.

Some journals are trying themselves to help readers discover marketing messages slipped in amid the scientific data. Last year BMJ, a British journal, published a piece called “Users’ guide to detecting misleading claims in clinical research reports,” which came with a picture of a reader dumping salt on a medical journal. One piece of advice: Beware when the authors break out one subgroup of patients and claim benefits from the treatment that weren’t evident in the whole group.

Dr. Kubota, a 26-year Kaiser veteran who holds a doctor of pharmacy degree from the University of Southern California, is based in the industrial city of Downey, southeast of Los Angeles, across the street from an abandoned movie set. Kaiser tries hard to keep her and her colleagues away from the influence of the companies whose products they evaluate. Before meeting with Dr. Kubota, a representative of a drug company must fill out a form indicating who will be coming, what they plan to discuss and why the information can’t be relayed in written form. No gift pens, mugs or other trinkets are allowed. Dr. Kubota’s business card doesn’t show her direct phone number.

When Dr. Kubota started her current job in 1997, she says she “would just read the abstract,” the summary at the beginning of a study. “I guess I was naive,” she says. “You kind of assume everything is there for you in the abstract.” Today, she quickly homes in on details that aren’t mentioned in the abstract and generates a 6-inch stack of papers studded with Post-it notes for each drug.

When she reviewed Adderall, a stimulant now marketed by Shire Pharmaceuticals Group PLC to treat attention deficit hyperactivity disorder, she noted that one of the major trials included only people who had responded well to Ritalin, another ADHD drug. She thought the move likely improved the results. Dr. Kubota recommended leaving Adderall off Kaiser’s formulary. The physician committees partially overruled her, putting Adderall on the Northern and Southern California formularies but only for patients who failed to respond to another stimulant. Adderall later was added to the preferred list as a first-line treatment after a once-daily formulation went on the market.

A spokesman for Shire, Matt Cabrey, said that the designers of the trial, which was conducted when Adderall belonged to another company, felt that for ethical reasons they should give the drug to people with a “reasonable anticipated reaction.” James Swanson, the lead author of the article that described the trial’s results, said the trial was designed to show whether Adderall works faster than Ritalin.

Girls With ADHD Are Often Overlooked

HealthNewsDigest.com – August 29, 2005 (HealthNewsDigest.com) reports that ADHD likely affects 3% to 7% of the entire child population in the US. However, girls are frequently overlooked because they often do not display hyperactive symptoms.

When teaching at the elementary level, I found this particularly true. Girls with ADHD often were simply daydreamers with poor time management skills. While some did display the outward social and behavioral problems that their male peers did, it was not very frequent.

HealthNewsDigest.com is published by the American Psychological Association. I’ve cited bits of this report and am alarmed by its look and feel. It reads like an endorsement and advertisement for Adderall XR.

Their report, edited down:

The federal Food and Drug Administrations (FDA) recent nod to ADDERALL XR for the treatment of attention deficit hyperactivity disorder (ADHD) in adolescents aged 13 to 17 spotlights an underidentified and under treated population with this disorder, experts tell Health NewsDigest.com.

If left untreated, the symptoms of ADHD can have a profound effect on a child’s life, both inside and outside of a classroom setting.

For Janice Lowder, a quiet, well-behaved child, learning was always stressful.

“My husband and I hired a one-on-one tutor to help Janice with her studies. We also tried to help her, and all dreaded the nightly battle of completing a homework assignment. Janice would get so frustrated with her homework and the fact that she didn’t ‘get it,’ that she would cry,” said her mother Beth Lowder.

“By the time Janice reached the seventh grade, a nurse at her school suggested we talk to a doctor. Janice was diagnosed with ADHD and was started on treatment,” Beth explained.

“I knew my daughter just needed the right help,” said Beth.

By the tenth grade, Janice had improved from a C to a B student but homework was still challenging. In addition, she had low self-esteem and was embarrassed to take her medication at school. Her psychiatrist prescribed Adderall XR®, an extended-release formulation that enabled Janice to take her medication once a day at home.

With continued tutoring and medication, her grades improved.

“She came home from school one day and said, ‘Mom, I’m smart,’” said her mother.

A recent study presented at the American Psychiatric Association annual meeting showed that girls with ADHD demonstrated significant improvement in both behavior and attention with Adderall XR.

“The study suggests that girls with ADHD can benefit from Adderall XR and that this treatment will help them control symptoms all day while they are in the classroom, during after-school activities or doing homework with relatively few side effects,” said Joseph Biederman, M.D., professor of psychiatry, Harvard Medical School and Chief of Pediatric Psychopharmacology at Massachusetts General Hospital. “While ADHD in girls is becoming more recognizable it is still often overlooked, and there is a need for safe and effective treatments that will allow girls to interact more effectively with other children and adults, to concentrate in school and to focus on finishing tasks.”

I’d expect to find a more diluted version in Parents Magazine or Family Journal as an outright advertisement. Makes one wonder who wrote this? Shire Pharmaceuticals?

Medical News Today reports that ADDERALL XR® from Shire Pharmaceuticals Group plc has been indicated for use among adolescents aged 13 to 17 with attention deficit hyperactivity disorder (ADHD) by the US Food and Drug Administration. (ADHD – FDA expands indication for ADDERALL XR® (CII) confirming safety and efficacy in adolescents)

The drug was originally approved for treatment in ADHD children aged 6 to 12 years in October of 2001 and since August 2004 in adults 18 years and older. ADDERALL XR is currently the most commonly prescribed brand of ADHD medication in the United States.

“There has long been an unmet need for ADHD research and treatment among the adolescent population despite an increasing awareness of ADHD’s potential impact on quality of life. Therefore, approval of an ADHD treatment for this underidentified age group is an important milestone,” explained Dr. Timothy Wilens of Massachusetts General Hospital. “The symptoms of ADHD often continue past childhood into adolescence and adulthood, where they can have a significant impact on an individual’s family, academic performance, and overall quality of life. Stimulant therapies are effective and generally well tolerated, and have been used medically in patients for more than 60 years.”

This directly contrasts with Health Canada’s decision to remove ADDERALL from the Canadian market (Health Canada Suspends ADHD drug Adderall XR) due to 20 or so deaths associated with the drug’s use. According to Shire Pharmaceuticals, “ADDERALL XR may not be right for everyone. ADDERALL XR was generally well tolerated in clinical studies. The most common adverse events in pediatric trials included loss of appetite, insomnia, abdominal pain, and emotional lability. The most common side effects in the adolescent trial included loss of appetite, insomnia, abdominal pain, and weight loss. The most common adverse events in the adult trial included dry mouth, loss of appetite, insomnia, headache, and weight loss.

The effectiveness of ADDERALL XR for long-term use has not been systematically evaluated in controlled trials. As with other psychostimulants indicated for ADHD, there is a potential for exacerbating motor and phonic tics and Tourette’s syndrome. A side effect seen with the amphetamine class is psychosis. Caution also should be exercised in patients with a history of psychosis.”

One must wonder whether the side effects are worth using a drug whose efficacy has not been evaluated for long-term use. Terms like ‘emotional lability’ appear as an attempt to obfuscate. It is much clearer to say, ‘emotional change or breakdown.’

The FDA probes side effects of ADHD drugs Government plans to strengthen label warnings.

From CNN.com

Thursday, June 30, 2005; Posted: 11:27 a.m. EDT (15:27 GMT)

WASHINGTON (AP) – The government is planning to strengthen warnings about possible psychiatric side effects from Concerta and related treatments for attention deficit hyperactivity, and is probing whether other ADHD drugs need updating, too.

Concerta is a long-acting form of methylphenidate, sold generically and under the brand name Ritalin. For years, those drugs’ labels have listed possible psychiatric side effects, such as agitation, psychosis or transient depression.

But a routine Food and Drug Administration review of Concerta’s use in children turned up more reports of psychiatric reactions than anticipated, including some that aren’t explicitly labeled, such as suicidal thoughts, hallucinations and violent behavior. A subsequent review of all methylphenidate products found similar reports.

The FDA can’t say if the drugs actually causes those side effects – the reports are from a database of reactions reported by medication users that make such determinations very difficult.

But, in a statement posted on its Web site, the agency said it does intend to strengthen the labeled warnings for all methylphenidate products.

Currently, the drugs’ labels may downplay the seriousness of psychiatric side effects, and suggest they’re only a risk in people who’ve already experienced psychiatric disorders, wrote FDA drug safety evaluator Kathleen Phelan.

Indeed, stimulant drugs “may exacerbate symptoms and reveal them for the first time” in children with previously unrecognized psychiatric illnesses, she wrote.

But, among 36 cases of psychiatric side effects in child Concerta users, six report histories of psychiatric illness, three deny such histories and there’s no information on the rest, Phelan wrote. Further investigation is needed to determine if such side effects may also occur in people without underlying illness, she added.

FDA said it doesn’t intend to change the drugs’ labels right away. It is investigating whether similar behaviors are seen with additional ADHD treatments, such as Adderall and Strattera – to avoid people switching drugs over the concern “based on incomplete safety assessments,” said an FDA document prepared for a meeting of the agency’s scientific advisers on Thursday.

That probe should be finished early next year.

From a recent news story – Drug withdrawal weighs on Shire:

Shares in Shire Pharmaceuticals have fallen 10% after its best-selling drug was withdrawn from sale in Canada amid reports linking it to 20 sudden deaths.

Regulators said data showed 14 children and six adults had died after taking the usual recommended doses of hyperactivity treatment Adderall XR.

Shire said it disagreed with the findings and remained confident in the safety and effectiveness of the drug.

The Hampshire-based firm is the UK’s third largest pharmaceutical company.

Most sales of Adderall XR come from the US.

The US FDA has also issued a Public Health Advisory to notify healthcare professionals that Health Canada, the Canadian drug regulatory agency, has suspended the sale of Adderall XR in the Canadian market.

Adderall XR (amphetamine)
Audience: Neuropsychiatric and other healthcare professionals

FDA issued a Public Health Advisory to notify healthcare professionals that Health Canada, the Canadian drug regulatory agency, has suspended the sale of Adderall XR in the Canadian market. Adderall XR 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. 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. Adderall XR is approved in the United States for the treatment of adults and pediatric patients 6-12 years old with ADHD, and Adderall, the immediate release formulation of the drug, is approved for pediatric patients with ADHD.

More information can be found on the FDA Adderall and Adderall XR Information page.

FDA ALERT [2/09/2005] – Sudden Deaths in Children

Health Canada has suspended marketing of Adderall XR products 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.

More information can also be found on the FDA Patient Information Sheet: Adderall and Adderall XR Extended-Release Capsules and the Alert for Healthcare Professionals: Adderall and Adderall XR (amphetamine).

From the FDA prescribing information for Adderall:

Long-Term Use: The effectiveness of ADDERALL XR for long-term use, i.e., for more than 3 weeks in children and 4-weeks in adults, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use ADDERALL XR™ for extended periods should periodically re-evaluate the longterm usefulness of the drug for the individual patient.