Major Drug Effectiveness Review Found “Little Evidence” that ADHD drugs are safe or effective

Tue, 13 Sep 2005

On paper, drug manufacturers MUST demonstrate with scientific evidence that a drug is safe and effective–if they want to gain to gain FDA approval. The burden of proof is on the manufacturer. That’s the law. The preferred method for demonstrating scientifically that a drug is safe and effective is by conducting controlled, randomized trial (CRT) . The FDA requires evidence from two CRT trials that a drug is safe and effective.

But strange things have been happening in the last dedade or so– The FDA has given its seal of approval to drugs, such as the antidepressants, psychostimulants (which are equivalent to speed), and antipsychotics, which have failed to demonstrate they are in fact safe or effective. The drugs have failed even in trials designed and controlled entirely by their manufacturer.

The Tacoma News Tribune reports about the latest independent review of ADHD studies by the Oregon Drug Effectiveness Review Project (ODER). The ODER findings confirm the findings of earlier independent reviews that found no evidence to support the claims about these drugs’ safety or the legitimacy of the ADHD diagnosis. For example, in 1998 The National Institutes of Health convened a panel of experts to answer just those questions about ADHD: the panel examined the body of evidence, heard testimony from experts on all sides and failed to reach a consensus about either the diagnosis or treatment.

In its final statement the 1998 NIH panel of experts acknowledged: “The risks of treatment, particularly the use of stimulant medication, are of considerable interest. Substantial evidence exists of wide variations in the use of psychostimulants across communities and physicians, suggesting no consensus among practitioners regarding which ADHD patients should be treated with psychostimulants… However, there is no evidence regarding the appropriate ADHD diagnostic threshold above which the benefits of psychostimulant therapy outweigh the risks….Finally, after years of clinical research and experience with ADHD, our knowledge about the cause or causes of ADHD remains largely speculative.”

In 1999, the Agency for Healthcare Research and Quality (AHRQ, formerly Agency for Health Care Policy & Research) conducted a review of 78 peer reviewed, published, ADHD CRT studies and found the studies of such poor quality AHRQ could not find evidence to support the claims made about the drugs.

Other assessments in 2000 and 2001 came to the same conclusions: there is no evidence to justify exposing children to psychstimualnt drugs that may adversely affect their neurological development.

So, in light of the fact that ADHD drugs have been tested in 2,287 studies – “virtually every investigation ever done on ADHD drugs anywhere in the world”–and they have failed to demonstrate safety or effectiveness, the following statement is irrational:

“The findings do not mean ADHD drugs are unsafe or unhelpful, just that sound scientific proof is lacking.”

See: “Broken Brains or Flawed Studies? A Critical Review of ADHD Neuroimaging Research” Jonathan Leo, Western University of Health Sciences and David Cohen,* Florida International University The Journal of Mind and Behavior, Winter 2003, Volume 24, Number 1, Pages 29 – 56.

*Dr. David Cohen is a board member of AHRP

Contact: Vera Hassner Sharav
212-595-8974

http://www.thenewstribune.com/health/story/5174762p-4705010c.html

Tacoma, WA – Tuesday, September 13, 2005
Are ADHD drugs safe? Report finds little proof
M. ALEXANDER OTTO; The News Tribune
Last updated: September 13th, 2005 11:35 AM (PDT)

At a time when millions of children and adults are taking drugs for Attention Deficit Hyperactivity Disorder, the most comprehensive scientific analysis of the drugs to date has found little evidence that they are safe, that one drug is more effective than another or that they help school performance.

The 27 drugs studied included Adderall, Concerta, Strattera, Ritalin, Focalin, Cylert, Provigil, and others that, in some households, are well-known for their sometimes calming affects.

The 731-page report was done by the Drug Effectiveness Review Project, based at Oregon State University. The group analyzed 2,287 studies – virtually every investigation ever done on ADHD drugs anywhere in the world – to reach its conclusions.

They found:

• “No evidence on long-term safety of drugs used to treat ADHD in young children” or adolescents.
• “Good quality evidence … is lacking” that ADHD drugs improve “global academic performance, consequences of risky behaviors, social achievements” and other measures.
• Safety evidence is of “poor quality,” including research into the possibility that some ADHD drugs could stunt growth, one of the greatest concerns of parents.
• Evidence that ADHD drugs help adults “is not compelling,” nor is evidence that one drug “is more tolerable than another.”
• The way the drugs work is, in most cases, not well understood.

The findings do not mean ADHD drugs are unsafe or unhelpful, just that sound scientific proof is lacking.

The Pharmaceutical Research and Manufacturers of America, the Washington, D.C.-based drug industry lobby group, had no comment on the report, but its senior vice president, Ken Johnson, said the benefits of most drugs “clearly outweigh the risks.”

ADHD is suspected when people have a harder time than others their ages paying attention, sitting still or controlling impulses. To be diagnosed, those tendencies must interfere with work, school or other activities.

Nationally, about 4.4 million kids between 4 and 17 fit the bill. Of those, more than 2.5 million take ADHD drugs. Up to 8 percent of kids in Washington state have been diagnosed with the condition.

The Drug Effectiveness Review Project was formed in 2003 to give consumers and state insurance plans trustworthy information about pharmaceuticals.

Industry studies, which researchers have shown sometimes are rigged for favorable outcomes, don’t give the confidence “many of us would like to decide whether or not we should be using a given medication,” said the project’s deputy director, Mark Gibson.

Complicating efforts to get reliable information, the U.S. Food and Drug Administration doesn’t require companies to compare new drugs to ones on the market. Most times, firms instead compare their wares to sugar pills because it is easier to show benefit and get approved for sale.

The problems leave insurers and patients in the lurch when they need to know what drugs work best. That’s where the Drug Effectiveness Review Project comes in. Its physicians and pharmacists analyze virtually every study on a given class of pharmaceuticals to find the best drugs.

The American Association of Retired Persons and Consumers Union, the publisher of Consumer Reports, use the project’s findings to tell people what drugs give the most for the money. Fourteen states, including Washington, also use its services to decide what drugs to cover for beneficiaries. Those states are the project’s chief funders.

For ADHD, the project analyzed published studies as well as unpublished data from the six leading makers of ADHD drugs. The group rejected 2,107 investigations as unreliable, and reviewed the remaining 180 to find superior drugs.

Instead, it found that evidence to choose one drug over another for safety or effectiveness is “severely limited” by a lack of studies measuring “functional or long-term outcomes.”

The project could not find a “good quality” study that tested the drugs against each other. It also could not find comparative evidence to determine which ADHD drugs are less likely to cause tics, seizures and heart and liver problems.

That evidence is needed. Canadian authorities have recently warned against using Adderall Extended Release in patients with heart problems. Cylert and Strattera have been linked to liver damage, the report said.

Until better research is done, the findings mean that choosing the right ADHD drug is largely a matter of trial and error. They also suggest some people might do as well or better on cheap generic Ritalin, sold by its scientific name methylphenidate, instead of far more expensive, newer options such as Concerta and Adderall.

In fact, in the few instances where the Oregon group could draw conclusions, it found Concerta “did not show overall difference in outcomes” compared to generic Ritalin, and proof that Adderall is better “lacking.” What little evidence there is comparing another newer expensive drug, Strattera, to generic Ritalin “suggests a lack of difference in efficacy.”

Gibson cautioned that his project’s latest report is still open for public comment and possible fine-tuning. But the overall results did not surprise Libby Munn, a nurse practitioner at Greater Lakes Mental Healthcare in Lakewood.

“I’ve never been aware of any evidence of any one being better than another,” said Munn, who treats patients for ADHD and other conditions. “That’s true of antidepressants and antipsychotics, too. Once you compare meds for a given disorder, there are often no proven differences.”

Tacoma psychiatrist Dr. Fletcher Taylor, an expert in adult ADHD at Rainier Associates, works with drug companies to develop new products. He said he stands by the effectiveness and safety of the drugs.

Still, he said, Adderall and Concerta are largely equal in their effect, though some people do better on one than another. Their greatest advantage over generic Ritalin is that people take fewer pills during the day.

ADHD DRUG COSTS*

• Methylphenidate (generic Ritalin) $15.69
• Ritalin (brand name): $27.79
• Amphetamine/dextroamphetamine (generic Adderall): $47.09
• Adderall (brand name): $94.49
• Concerta: $103.99
• Strattera: $123.99
• Focalin: $25.99

*Comparisons based on the lowest dose for 30 days.

Source: Walgreens Pharmacy

FIND THE RIGHT DRUG

These Web sites offer help comparing drugs to find what works best:

• The American Association of Retired Persons lets you compare drugs at www.aarp.org/health/comparedrugs/
• Consumers Union, the publishers of Consumer Reports, gives tips on the best drug buys for safety and effect at www.crbestbuydrugs.org/
• The consumer-advocacy group Public Citizen has a solid record of spotting problem drugs, calling, for instance, for the removal of Vioxx in 2001, when few knew there were problems. The group is now worried about the cholesterol pill Crestor. Public Citizen’s drug information site is www.worstpills.org/
• The Oregon State University Drug Effectiveness Review Project is online at www.ohsu.edu/drugeffectiveness/

M. Alexander Otto: 253-597-8616

Originally published: September 13th, 2005 12:01 AM (PDT)

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