| The Under Reported Story: ADHD, Stimulants, and the FDA |
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by Grace E. Jackson,
MD It was only eight months ago that the FDA convened a similar hearing, partly in response to Health Canada’s decision to remove Adderall XR from the market in early 2005. Although foreign authorities later rescinded that decision, concerns about the cardiovascular risks of Adderall and other stimulants remained. Dramatic media announcements preceded last June’s deliberations, but the FDA leadership assured the public that no new warnings were warranted. In their latest interviews with the press, FDA panelists
cited a figure of 25 deaths (1999-2003) among American stimulant users, but 51
deaths are listed in an agency staff report.
According to
California
neurologist, Dr. Fred Baughman, his Freedom of Information Act request revealed
186 deaths in the MedWatch database between 1990 and 2000. Given the fact that a mere 1% of all adverse
events are believed to be filed with the FDA under the nation’s voluntary
reporting system, the true scope of stimulant lethality is much larger than the
regulatory agency concedes. Unfortunately for consumers, the cardiovascular risks of stimulants are hardly new. As early as 1977, Drs. Vernon Fischer and Hendrick Barner documented the cell changes associated with heart muscle enlargement in a chronic consumer of Ritalin (methylphenidate). Those findings were based upon a tissue biopsy obtained from the patient during bypass surgery. Intrigued by this discovery, Fischer teamed up Theodore Henderson in 1995 to publish the results of several animal experiments involving Ritalin. Their research confirmed a causal link between normal doses of the stimulant and the appearance of persistent heart cell abnormalities, identical to the changes observed in humans. The connection between stimulants, cardiovascular disability, and death has long been documented in the medical literature, but physicians and government regulators have refused to acknowledge the hazards associated with prescriptions. In 2000, the FDA asked manufacturers to voluntarily remove the stimulant ingredient, phenylpropanolamine, from cold remedies and over-the-counter products used for weight control. In 2004, the FDA issued a rule to prohibit the sale of dietary supplements containing the stimulant, ephedra (ma huang). On January 13th 2006, the FDA issued a warning about the importation of Brazilian diet pills which contain a stimulant called Fenproporex. Each of these regulatory decisions stands in striking contrast to the agency’s ambivalence about stronger warnings on the labels of ADHD drugs. Many facts about stimulant medications, and the ADHD
industry which sustains them, are commonly misreported or undisclosed. One example is the secret identity of atomoxetine (Strattera), a selective
norepinephrine reuptake inhibitor approved by the FDA for children and adults in
2002. Widely marketed in the
United
States as the first “non-stimulant” for ADHD,
the fact is that the World Health Organization designates the compound as a
centrally acting sympathomimetic (psychostimulant), according to the
international drug classification system.
As neurologists at Stanford
University have noticed, atomoxetine
(and in Europe, the chemically similar reboxetine)
possesses stimulant properties which make it an effective treatment for the
sleep condition of narcolepsy. While this classification dispute may seem trivial on
the surface, it becomes salient in light of a recent report by
North Carolina
examiners who detected cardiac abnormalities in the autopsies of Strattera
patients. If the FDA ever does decide to add Black Box Warnings
about the vascular risks of stimulants, without acknowledging the true
physiological effects of Strattera, one can expect Lilly’s product to emerge as
the clear winner of this year’s safety lottery. A word about regulatory authority is also in order. Contrary to the usual media reports, a Black
Box Warning – which refers to the appearance of an explicit safety alert on the
product label of a medication or medical device – is not the strongest precautionary measure in
the Food and Drug Administration arsenal.
The agency may require wording which outlines contraindications. These are statements about specific
conditions or populations for which a medical product or device must not be used. Beyond the identification of
contraindications, however, the FDA may issue advisories, enact rules, or
implement enforcement decisions.
Ultimately, the agency may initiate actions to remove a product from the
market. Reflective observers are wondering at this point why stimulants have not been removed from the market
as a treatment for ADHD.
Their concerns include the preliminary findings of Texan investigators,
whose 2005 report in the journal Cancer
Letters documented the emergence of chromosomal abnormalities in 12
out of 12 juveniles following three months of treatment with Ritalin. The unreported story is what happened
after the behind-the-scenes
scramble by officials from the FDA and other governmental bodies, who were
dispatched to Houston
last May in an effort to establish the validity of the methods and data of the
Texan team. Subsequently authenticated,
the implications of that research (namely, that Ritalin exposure in childhood
may induce changes associated with higher risks of cancer) have been serious
enough to trigger follow-up studies at other facilities. FDA leaders continue to affirm that new warnings on
stimulants are unnecessary. As Dr. Thomas Laughren and others have recently opined,
ADHD is a serious medical condition for which the benefits of stimulant drug
therapy outweigh the conceivable risks.
Whether by ignorance or design, however, the regulators remain oblivious
to the evidence-based limitations of the prescription pad: at least 40%
of all children fail to tolerate or respond to stimulant therapy; about
twice as many respond at least as well to non-pharmacological interventions;
and, as documented in the National Institute of Mental Health’s most prestigious
study to date (the MTA study), the long term outcomes for medicated children
demonstrate diminishing returns over time, persistent suppression of growth
(about 1 cm per year), and artificial behavioral improvements which dissipate
when treatment is withdrawn. The FDA and others are disingenuous when they ignore the
contentious nature of identifying ADHD as a neurological disorder for which
medications are the best solution. A
strong body of evidence now challenges both assertions. Clinicians question the ethic of drugging
children and adults, in an effort
to suppress symptoms which may be interpreted as transient, developmental delays
(most children outgrow ADHD in their teens); normal variants of temperament;
contextually appropriate reactions; and/or the failure of caregivers, social
systems, or culture to assist others in maximizing their capacities for moral
agency and self-control. It is time for consumers, physicians, educators, and
policy makers to confront the distorted and missing information which surrounds
the phenomenon of ADHD. More members of
the medical community should doubt the legitimacy of the condition, since no
biological marker or diagnostic test has been found or devised. When interviewed, a majority of physicians
state that they would prefer not
to prescribe stimulants to children, due to the physical and psychological side
effects. Not surprisingly, the world
community observes the United
States with alarm for the unjustified chemical
exploitation of those who are different, but not diseased. References
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Doggett, A.M. (2004). ADHD and drug therapy: is it still a valid treatment ? Journal of Child Health Care, 8, 69-81.
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