Lilly says Ritalin alternative
shows significant promise
Alternative treats disorder without stimulants
By Thomas M. Burton
THE WALL STREET JOURNAL
October 26 (2000) For decades, it has been a Holy Grail
of medical research to find a treatment for
attention-deficit disorder that doesnt involve the
use of stimulants. Now, it appears that the goal is
at hand.
[Fred A. Baughman Jr., MD:
Speaking of Holy Grails, Lawrence Diller, author of Running on Ritalin
and a conferee at the DEA Conference on Stimulant Use in the Treatment
of ADHD, December, 10-12, 1996, wrote, "The reason why you have been
unable to obtain any articles or studies presenting clear and confirming
evidence of a physical or chemical abnormality associated with ADHD is
that there are none. Not that medical science, especially in recent
years, hasnt tried. However the search for a biological marker is
doomed from the outset because of the contradictions and ambiguities of
the diagnostic construct of ADHD as defined by the DSM. I liken efforts
to discover a marker to the search for the Holy Grail." ]
Research on an Eli Lilly & Co. drug, to be made public
in New York Thursday at a child-psychiatry conference,
suggests the medicine improves concentration to a degree
similar to that of Ritalin, the primary treatment for
attention-deficit disorder, or ADD. Unlike Ritalin and other
treatments, the Lilly drug, tomoxetine, isnt a stimulant.
Researchers say it doesnt trigger sleeplessness and has
relatively little tendency to suppress appetites.
[Fred A. Baughman Jr., MD:
These are things CHADD says Ritalin never does]
ADD is often
characterized by an inability to concentrate and sometimes
by aggression and hyperactivity.
"This will open windows for patients who would
otherwise not be medicated," says Joseph Biederman, the
chief of pediatric psychopharmacology at Massachusetts
General Hospital, in Boston, who ran the recent study on
tomoxetine.
[Fred A. Baughman Jr., MD:
Pharmacology, clinical: the branch of pharmacology concerned with the
pharmacology of therapeutic agents in the prevention, treatment and
control of diseases in man (Stedmans, 25th Edition). In that
psychopharmacology deals not with diseases (disease = abnormality),
but with emotional/behavioral problems in normal (normal = no disease)
persons, it cannot be considered a branch of clinical pharmacology.
They are quite fond of framing everything they do in medical/biological
terms when there is no biology andthere being no diseasesthere is
nothing medical. The specialty of pediatric psychopharmacology is
that which give brain-altering, brain-damaging drugs to normal infants,
toddlers and children with emotional/behavioral problems. That is, the
infants, toddlers, and children were normal until the foreign
compounds/drugs, targeting no known abnormality, were begun. Yet
another definition I have come across impresses. Pharmacomania:
(Dorland, 21st Edition) abnormal fondness for taking or administering
drugs. This, it would seem is endemic in only the North American mental
health industry at the turn of the century. 96% of Ritalin/amphetamine
use in the world, virtually all of it in children, for the fraudulent
diseaseADHD, is in North America]
These findings place Lilly, of Indianapolis, at the front
of the pharmaceutical footrace to treat ADD and
closely-related ADHD, attention deficit/hyperactivity
disorder. Glaxo Wellcome PLCs U.S. unit is in the race,
too, and also is presenting research results Friday of its own
new drug, called GW320659; Glaxo says the drug is also
being studied for its effectiveness against other illnesses.
Another entrant is Abbott Laboratories, but Abbott hasnt
started testing its ADD drug in humans.
For Lilly, tomoxetine could provide a badly needed
boost. Its leading product, the antidepressant Prozac, will
lose patent protection next August unless the company
prevails on appeal of a patent lawsuit.
"The market could easily exceed $1 billion for a
product like tomoxetine," says independent
medical-industry analyst Hemant K. Shah. "Ritalin has such
a bad name that it would not be that difficult to convert
people to a nonstimulant." Ritalin, a Novartis AG brand
name for a controlled substance whose use is monitored by
law enforcement authorities, is one of several drugs that
critics have said are overprescribed for children. About 11
million prescriptions for Ritalin and its generic equivalents
were written in the U.S. last year, for an estimated 1 million
to 1.5 million patients, mostly children. Since more than
80% of these were for the generic version, called
methylphenidate, the 1999 sales in dollars were only $400
million. The entire category of stimulant drugs to treat ADD,
including Adderall and Dexedrine, has generated sales of
more than $900 million during the most recent 12 months.
Mr. Shah estimates that a high percentage of Ritalin
patients would switch to an alternative. Moreover, about
30% of ADD patients dont respond to Ritalin or any of the
stimulant drugs, and about 50% have difficulties with side
effects, primarily insomnia and appetite suppression.
The Lilly clinical studies are considered Phase II,
meaning one more stage of research is needed for the Food
and Drug Administration to consider approval. Things could
still go wrong for Lilly. However, there were already 127
children involved in the research a relatively large
number and the findings were compelling. Youngsters on
tomoxetine had nearly three times the improvement of
children taking a placebo. Their improvement nearly
matched that with Ritalin.
The studys results regarding insomnia were powerful in
favor of tomoxetine: Among Ritalin patients, 27% had
insomnia, as did 9% of patients on a placebo. Only 7% of
patients on tomoxetine reported insomnia.
"I truly think were going to be the first company to
bring a nonstimulant alternative to the market," says John H.
Heiligenstein, a Lilly research physician who first suggested
using the drug in attention-deficit children.
Joseph DeVeaugh-Geiss, Glaxo vice president of
neurology and psychiatry-clinical research, agrees, "Were
not as advanced in development as they are." He says,
though, that Glaxo has had "really good response" with its
new drug and that about 76% of 46 child patients
responded to the Glaxo medication. (Glaxos results to be
made public Friday dont include a placebo group for
comparison.)
ADD has been the topic of controversy for years.
Many have debated whether it truly is a medical condition.
British doctor who identified it in 1902 thought it
stemmed from what he called a "defect in moral control."
More recently, many Americans have grown convinced the
condition is at least overdiagnosed and that many children
are overmedicated. In May, a Dallas law firm filed a
would-be class action in state court in Brownsville, Texas,
alleging Novartis overpromoted Ritalin and failed to disclose
adequately a range of side effects of the drug. Novartis
called the suit "without merit."
Even so, there is increasing evidence that in perhaps as
many as 3% to 5% of children and in some adults ADD
does exist and is triggered by abnormal activity in the brain.
It has been known for decades that insufficient amounts
of the brain chemical dopamine play a role in ADD.
[Fred A. Baughman Jr., MD:
This is an industry-planted piece without a doubt. Here they sayand
you must read this carefully: "It has been known for decades that
insufficient amounts of the brain chemical
dopamine play a role in ADD." No such thing has ever been proven. No
physical or chemical defect has ever been proven validating ADD (by
whatever acronym) as a disease, with objective abnormality = disease]
Within the
last decades, evidence has accumulated that deficiency of
another brain chemical, norepinephrine, also is involved.
[Fred A. Baughman Jr., MD:
If the first lie doesnt fly, try another. Nor does proof exist of a
defect of norepinephrine.]
The precise
role of both is uncertain, but a physiological cause of the
condition appears more and more likely.
[Fred A. Baughman Jr., MD:
And here we have the caveat: "The precise role of both is uncertain."
As they well know, the role of both is unproven! They as much as
confess this in saying "a physiological cause of the condition appears
more and more likely." Is this not deception?]
Stimulants such as amphetamines have been the
dominant form of treatment since the 1930s, when their
effects on ADD were discovered by accident. Ritalin,
introduced in 1955, primarily works by increasing dopamine
levels. But side effects also have been a problem, and
efforts to find a drug that avoided them have fallen short
until now. One drug, desipramine, an antidepressant used to
treat ADD in the 1980s, worked well, but a handful of
sudden cardiac deaths occurred in children, and
desipramines use for the condition almost stopped
overnight about a decade ago.
[Fred A. Baughman Jr., MD:
Psychiatrist John Werry of New Zealand called for an embargo of
desipramine in 1995 but was shouted down by US psychiatrists, Biederman,
et al, of the Mass General drugging unit. Despite the
no-one-knows-how-many sudden cardiac deaths there were in normal
children with emtional/behavioral problems, due to desipramine, its
continued availability was thus assured. The ever-present question
remains: how can physicians (psychiatrists among them) serve their
pharmaceutical masters and their human patients at the same time.
Increasingly, I am of the opinion that they absolutely cannot.]
An Abbott drug called
Cylert, introduced in the mid-1970s, showed great promise
but quickly fell out of favor because of acute liver toxicity.
[Fred A. Baughman Jr., MD:
Liver deaths, and liver transplants as the only way to avoid death.
"acute liver toxicity" doesnt quite tell the story. Furthermore, the
actual numbers of such deaths and transplants was continually
understated. In Canada, where the government still values human life
more than industry dollars with which to fuel political machinery,
Cylert was removed from the market. But here in the USA, the FDA, a
sham as a protector of the public, has seen to it that Cylert remains
available. After all there is so much ADD/ADHD yet to be treatedevery
last one of them normal until the drugging starts.]
Researchers also tested the new class of antidepressants,
such as Prozac and Zoloft, in ADD patients, with generally
unsatisfactory results.
Early in the 1990s, Lillys Dr. Heiligenstein, a
pediatrician and child psychiatrist, developed his own ideas
about ADD and its causes.
[Fred A. Baughman Jr., MD:
LillyDr. Heiligenstein, where exactly (cite the article, articles) is
the proof that ADD/ADHD exists? Where is the proof that the children
being targeted by industry and all of psychiatry for these drugs and
nothing else are other than normal when labeled. (in that no disease =
abnormality is proven, demonstrated, we should be loathe to use the term
[diagnosed]
He was convinced that a drug
that worked just on norepinephrine might treat ADD
without the stimulants side effects. Tomoxetine, originally
developed to be an antidepressant, was such a drug, so he
convinced the Mass General researchers to try it.
The research group had to move fast: The last batch of
tomoxetine usable in clinical tests was due to hit its
expiration date in April 1995. If researchers couldnt prove
to company executives tomoxetines usefulness by then, it
would be abandoned. But the first test of the drug, in adults,
was encouraging. Lilly decided to continue testing it. The
next stage, testing in children, is the one whose results are
being made public Thursday.
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