Evelyn Pringle March 20, 2006
A study published online in the February 2006, Journal of Drug and Alcohol Dependence, that examined data from a 2002 survey of about 67,000 households, estimates that more than 7 million Americans have misused stimulant drugs meant to treat ADHD, and “substantial numbers of teenagers and young adults appear to show signs of addiction, according to a comprehensive national analysis tracking such abuse.”
The statistics are alarming because people are using the drugs recreationally or to boost academic and professional performance. The scientists who published the study concluded that about 1.6 million teenagers and young adults had misused these stimulants during a 12-month period and that 75,000 showed signs of addiction.
Last month, the FDA's Drug Safety and Risk Management Advisory Committee held 2 days of hearings, and after listening to all the testimony and reviewing the data presented, recommended that all ADHD drugs carry a black box warning on increased cardiovascular risks.
This month, the Pediatric Advisory Committee is meeting on March 22, 2006, and will focus on neuropsychiatric adverse event reports and trial data on ADHD medications. The committee will also receive an update on efforts to better understand cardiovascular adverse events possibly related to ADHD medications, according to the FDA web site.
During the hearings last month, the Alliance for Human Research Protection, asked the FDA to issue (1) a public advisory; (2) a "dear doctor" letter to every doctor in America to apprise them of the essentially lethal side effects that are being tracked; and (3) to solicit the reporting of any and all adverse events of which they are aware.
Allen Jones, speaking as a representative of the Alliance, told the panel the FDA should instruct the pharmaceutical industry to advise the FDA of all adverse events that have been reported concerning ADHD drugs immediately, and also it should demand that all clinical trials in possession of the drug companies be turned over to the FDA so that independent researchers can review them for adverse events.
"We don't have the luxury of time to wait for the future trials," he pointed out. "Children are dying," he said.
Ellen Liversridge, having lost her son to side effects of the drug Zyprexa before they were made known in a black box warnings, appeared to speak on behalf of all parents who have lost their children due to adverse reactions to prescription drugs.
“I grieve particularly today for the 51 dead of ADHD drugs that were announced yesterday by the FDA,” she told the panel.
“I guess my up-front message, front and center,” she continued, “is that you know that ADHD drugs can cause serious side effects and death, including sudden death, hypertension, myocardial infarction, stroke, and possibly bipolar disorder.
“This being the case,” she said, “I urge you to recommend that these drugs have an appropriate black box warning placed on the label starting immediately.”
Sandra Lucas, appeared at the hearing to speak on behalf of the Citizens Commission on Human Rights, a psychiatric watchdog group, and told the panel, “we do know that the side effects of the stimulants are not only present, they are extremely serious and sometimes lethal.”
“So,“ she asked the committee, “while the FDA ponders the problem of studying the issue and conducting the studies that may have inherent flaws, what real, immediate protections are to be put in place for parents and children?”
During the hearing, Drug Safety panel member, Dr Art Levin, told the committee, “I think we have to recognize that when a drug is approved and marketed the public assumes a level of comfort in the safety of that drug unless they are told otherwise.”
“And, for us to sit around and talk about this,” he continued, “to have three advisory committee meetings discussing the signals and not to make, at the very least, a very strong warning to people that there is uncertainty here about the safety of these drugs and that they need to be aware of that pending clarification I just think is inappropriate, unethical behavior.”
Committee member, Dr Steve Nissan advised, “we have to elevate the level of concern and if it slows the growth of this, that is probably appropriate because I think most observers would argue that ten percent of ten year-olds do not have this disease and what has happened is that this is out-of-control use of drugs that have profound cardiovascular effects and, as a cardiologist, I can tell you that,” he said.
Panel member, Dr Curt Furberg, recommended that ADHD drugs also come with a patient guide “so that when parents are filling prescriptions for their kids they get a written document laying out the state of knowledge, or lack of the state of knowledge and the potential risks so they are reminded each time that there is a potential risk and we are trying to find solutions to it,” he advised.
Since last month’s recommendation for a black box warning on cardiovascular events, FDA reviewers announced a recommendation for stronger warnings on all ADHD drugs due to reports of numerous adverse events like mania and psychosis in clinical trials, including modafinil.
On March 14, 2006, an FDA review was posted to the agency's web site in advance of next week's meeting. The FDA said stronger warnings are needed on the risk of psychosis, a mental disorder characterized by the inability to distinguish real and imaginary events.
"The most important finding of this review is that signs of psychosis or mania, particularly hallucinations, can occur in patients with no identifiable risk factors, at usual doses of any of the drugs used to treat ADHD," according to a memo dated March 3 from two members of the agency's ADHD psychiatric review team.
The review said current labeling neither addresses those concerns nor does it "clearly state the importance of stopping drug therapy in any patient who develops hallucinations or other signs or symptoms of psychosis or mania during drug treatment of ADHD."
From January 2000, through June 30, 2005, the review found nearly 1,000 reports of psychosis or mania possibly linked to the drugs, including Adderall, Concerta, Ritalin and Strattera. The reports were pulled from the FDA's database and from the drug makers themselves after the FDA had requested additional information from the drug companies.
The FDA found a "substantial portion of the psychosis-related cases were reported to occur in children 10 years or less," an age group which according to the FDA, does not typically suffer from psychosis.
"The predominance in young children of hallucinations, both visual and tactile, involving insects, snakes and worms is striking and deserves further evaluation," the FDA noted.
Last fall, on September 29, 2005, the FDA issued a public health advisory to alert physicians of reports of suicidal thinking in children and adolescents associated with Strattera, and directed Eli Lilly, manufacturer of Strattera, to develop a Medication Guide for patients and caregivers.
Although Strattera is marketed as a "nonstimulant" medication, according to pediatrician, Dr DuBose Ravenel, MD, FAAP, of Cornerstone Pediatrics, “it is in fact a stimulant every bit as much as the traditional stimulants, as evidenced by even a cursory consideration of its pharmacological action, and evidenced by the fact that it is classified as such by the World Health Organization.”
Dr Fred Baughman, ADHD expert and well-known author, will testify before the committee next week on behalf of the International Center for the Study of Psychiatry and Psychology.
“We know these drugs are poisons,” Dr Bughman warns, “and we know they are highly addictive, dangerous and sometimes deadly.” He points to the senseless death of children on ADHD drugs. “Matthew Smith is dead today not because of ADHD,” he says, “but, as carefully delineated by the medical examiner, his chronic Ritalin/methylphenidate exposure.”
“Nor is there any other plausible explanation for the death of Stephanie Hall, 11 years old of Canton, OH,” he advises. “No physical predisposing factor other than Ritalin was present,” he notes, “leading up to her death, in bed, by cardiac arrhythmia.”
“The main question the FDA needs to answer concerns ADHD,” Dr Baughman says, “the "disorder" these addictive, dangerous, sometimes deadly drugs are used to treat.”
“The shocking fact of the matter is that it is not a disorder/disease at all,” he explains, “children said to have it are entirely normal meaning they bear no objective, demonstrable, diagnosable, abnormality, meaning there is no justification for prescribing these or any other drugs for so-called ADHD--a wholly fictitious, wholly subjective entity.”
According to Dr David Stein, Ph D, Professor of Psychology at Longwood University, “the risks of psychiatric drugs in the bodies of children and teenagers is well documented and needs no further elaboration.”
He wants the advisory committee to address two issues: (1) the validity of ADD/ADHD as diseases; and (2) effective alternative behavioral treatments that reduce reliance on drugs.
Dr Stein’s behavioral/cognitive treatment methods have won awards from the American Psychological Association (One of top ten research projects at the 1998), the International Center for Psychiatry and Psychology (2005), and the Ritalin Litigation Conference (2001).
“It is my hope,” he says, “that the committee will consider that within the decision tree, the physician's choice to use drugs can be lowered in favor of, at the very least, recommending properly designed behavioral parent training.”
“The risks of legal liability and the risks of medical damage to children,” Dr Stein advises, “can be reduced with the augmentation and further development of proper behavioral treatments.”
According to court certified expert and author of many books on ADHD, Dr Peter Breggin, all stimulants commonly cause “a continuum of stimulation, including agitation and irritability, anger, hostility, disinhibition, hypomania and mania.”
The stimulant or activation syndrome, he advises, was originally observed decades ago with stimulant drugs such as amphetamines, Adderall, and Dexedrine, and methylphenidates such as Ritalin and Concerta.
It also occurs, he notes, with dexmethylphenidate such as Focalin, and selegilines like Sparlon and Provigil, as well as the atomoxetine, Strattera.
In a review of the summary data for the FDA Spontaneous Reporting System through March 1997, Dr Breggin counted the following: Psychosis, 43; hallucinations, 44; and psychotic depression, 11. His review also counted more than 50 reports in the combined category of overdose, overdose intentional, and suicide attempt.
“In regard to both amphetamines and methylphenidate,” he explains, “there are a surprising number of animal and human studies showing persistent biochemical changes and atrophy after several weeks or more exposure.”
“While the changes in children are sometimes mistakenly attributed to ADHD or OCD, they are a known effect of stimulants on the animal brain,” he advises. “A known toxic drug effect is a far more likely culprit than a highly speculative "biochemical imbalance" in these children,” he adds.
Dr Breggin will also testify at the advisory committee hearing on behalf of the International Center for Psychiatry and Psychology, and will recommend that labels for stimulant drugs include the following neuropsychiatric warnings:
(1) A warning concerning depressive/OCD ADRs that includes depression, apathy, lethargy, listlessness, tiredness, sadness, crying, withdrawal, and social isolation as well as worrying, ruminating, over-focusing, and other obsessive-compulsive behaviors.
(2) A warning concerning stimulation or activation ADRs that includes insomnia, anxiety, agitation, panic attacks, irritability, hostility, aggressiveness, violence, impulsivity, disinhibition, hypomania, and mania.
(3) Strengthened warning concerning psychosis, paranoid ideation and hallucinations.
(4) Strengthened warning about rebound, dependence and abuse, especially for methylphenidate products (all current methylphenidate labels especially inadequate).
(5) A specific warning that the combination of depressive, obsessive-compulsive and stimulant ADRs poses a serious risk of dyscontrol or disinhibition with suicidal and/or violent behavior.
(6) A warning in the labels for amphetamine and methylphenidate products about persistent brain dysfunction and atrophy.
Information released by the FDA last month showed that between 1999 and 2003, seventy-eight million prescriptions were written for ADHD drugs in children ages 1 to 18, and more than 14 million prescriptions were written for adults.
During last month’s hearings, Safety Drug committee member, Dr Steve Nissen, said he is certain the public is not aware of the risks. "If the current warnings were adequate we wouldn't have 2.5 million children and 1.5 million adults taking these drugs.”