Mon, 26 Apr 2004
A front page article in The Wall Street Journal (excerpt below) provides a roadmap of failed Eli Lilly drugs which the company repackaged for a different condition than the one for which the drugs had been tested in clinical trials, or to expand the market for drugs that don't bring in enough profits when marketed for a particular condition.
The Journal notes: "Lilly has long had a culture that looks at failure as an inevitable part of discovery and encourages scientists to take risks. If a new drug doesn't work out for its intended use, Lilly scientists are taught to look for new uses for a drug."
The Journal lists 8 failed Lilly drugs that were recycled or in the process of being recycled. Among the drugs that bombed are two antidepressants that have been repackaged.
Strattera and Cymbalta are antidepressants of the selective norepinephrine reuptake inhibitor (SNRI) class. In clinical trials Strattera had failed as an antidepressant, but is now marketed as a "non-stimulant" treatment for ADHD.
Cymbalta (duloxetine), a potent dual reuptake inhibitor of the neurotransmitters serotonin and norepinephrine also failed in its original antidepressant trials. It is now being tested for incontinence at higher doses.
The recycling of these failed antidepressants raises concerns because of evidence-from previously concealed clinical trial data and from a large number of case reports--all indicating that the newer generation of antidepressants can trigger serious adverse symptoms that can lead to life-threatening behavior in some patients. These unwanted effects include: movement disorders, withdrawal symptoms, mania, depression, hallucinations, agitation, aggressiveness, anxiety, psychosis, akathisia, and violent or suicidal behavior.
The FDA had evidence of these drugs' adverse effects for years but failed to warn prescribing physicians and the public. For example, a "confidential" October 1996 memo FDA's Dr. Thomas Laughren referred to an analysis by Dr. James Knudsen, FDA's own medical officer of four Zoloft (sertraline) pediatric trials:
"Dr. Knudsen provided person-time data only for the sertraline exposed patients, yielding adjusted estimates of 0.035/ PEY [patient exposure years] for adults and 0.25 /PEY for pediatric patients. He commented on the 7-fold greater incidence of Suicidality in children taking sertraline compared to adults." In this memo (obtained under Freedom of Information) Dr. Laughren acknowledges that 6 children in those Zoloft trials who were on the drug became suicidal.
On March 22, 2004 the agency issued a warning advisory about antidepressant drug risks only after it was learned that senior FDA officials had suppressed the release of an analysis by FDA's leading expert. That report, by Dr. Andrew Mosholder, validates the safety concerns and the unfavorable risk / benefit ratio of antidepressants for children.
Strattera is an SNRI--the same class of drugs as Effexor, whose manufacturer, Wyeth, issued a clear warning about the suicidal risk, advising physicians not to prescribe Effexor for children. Since it's launching in December 2002, Strattera is the fastest growing ADHD drug, capturing 16.3% of the market share in just 9 months. The cumulative number of prescriptions written for Strattera doubled during the third quarter, from roughly 1 million in the first half of 2003 to more than 2 million by the end of September 2003. It is estimated that of 1.4 million individuals, 856,000 children are prescribed Strattera. See: Psychiatric News. Med Check Compiled by Jim Rosack December 5, 2003 Volume 38 Number 23 http://pn.psychiatryonline.org/cgi/content/full/38/23/22
The Alliance for Human Research Protection is concerned that children who are prescribed the failed antidepressant, Strattera, may be exposed to undisclosed serious risks of harm.
FDA's-approved label states: "STRATTERA was administered to 2067 children or adolescent patients with ADHD and 270 adults with ADHD in clinical studies. Yet, adverse effects analysis included only 427 children on Stattera, and reported withdrawal of only 15 of 427 children on Strattera compared to 4 out of 294 children given a placebo. See: http://www.fda.gov/cder/foi/label/2002/21411_strattera_lbl.p df
What happened to the other 1,640 children who were administered Strattera?
AHRP questions FDA's inexplicable failure to include Strattera data in Dr. Andrew Mosholder's analysis of antidepressants-and we question the exclusion of Strattera from FDA's antidepressant drug advisory warning (March 22, 2004).
Surely FDA officials know that a drug described in FDA's approved
Strattera label as a "selective norepinephrine reuptake inhibitor" is
similar to several other SNRI drugs approved and marketed as antidepressants.
Whether a drug is prescribed for children with depression or ADHD, the
drug's potential adverse effects are the same.
See: THE LOS ANGELES TIMES. A Godsend, Till a Life Unravels By Alan Zarembo and Benedict Carey, April 2, 2004 http://www.latimes.com/news/science/la-sci-humantest2apr02,1 ,6542363.story?coll=la-home-headlines
Contact: Vera Hassner Sharav
Tel: 212-595-8974
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Wall Street Journal
Flop Factor: By Learning From Failures, Lilly Keeps Drug Pipeline Full;
Dr. Nyikiza Uses Math Skills To Save Cancer Treatment; A Surprisingly
Simple Fix; Lessons of an Antelope Hunt By Thomas M. Burton Apr 21,
2004 A.1
INDIANAPOLIS -- Five years ago, Eli Lilly & Co. had high hopes for an experimental chemotherapy drug called Alimta. But after three patients taking Alimta died suddenly in 1999, Lilly halted trials of the drug. It looked like a fatal blow for Alimta -- despite strong evidence that it could reverse tumor growth.
Paolo Paoletti, the Lilly doctor running the trials, begged for two weeks to save the drug. He teamed up with a Rwandan mathematician, Clet Nyikiza, whom Lilly keeps on staff largely to study drug failures. Dr. Nyikiza had been fascinated by why complex processes fail ever since his grandfather taught him as a boy in East Africa the telltale signs of an unsuccessful antelope hunt. By analyzing blood samples and medical records, Messrs. Paoletti and Nyikiza identified a surprising problem with an unexpectedly simple solution.
Today, Alimta is an approved treatment for mesothelioma, a rare type of cancer caused by exposure to asbestos. It's under Food and Drug Administration consideration as a treatment for lung cancer, a much more common ailment.
Alimta's resurrection helps illustrate why Lilly is coming out with a flood of new medicines even as many of its competitors struggle to replace blockbuster drugs coming off patent. Lilly has long had a culture that looks at failure as an inevitable part of discovery and encourages scientists to take risks. If a new drug doesn't work out for its intended use, Lilly scientists are taught to look for new uses for a drug. In the early 1990s, W. Leigh Thompson, Lilly's chief scientific officer, initiated "failure parties" to commemorate excellent scientific work, done efficiently, that nevertheless resulted in failure.
Other drug companies are also seeing the importance of tolerating - and learning from -- failure, a valuable strategy since about 90% of experimental drugs in the industry fail. For example, Pfizer Inc. originally developed the blockbuster impotence drug Viagra to treat angina, or severe heart pain.
Lilly has taken this approach to unusual lengths. It assigns someone --often a team of doctors and scientists -- to retrospectively analyze every compound that has failed at any point in human clinical trials. Blair Sheppard, a management professor at Duke University who's done Consulting work for Lilly and other pharmaceutical companies, says that Lilly developed "a formalized and thoughtful process in which it reviewed failures more honestly, more deeply and started the process sooner than anyone else."
Many Lilly drugs have risen from failure. Evista, now a billion- a-year drug for osteoporosis, was a failed contraceptive. Strattera, a hot-selling drug for attention deficit/hyperactivity disorder, bombed out as an antidepressant.
There's a name for it - it eludes me. Something akin to "restless leg". It's almost like an anti-spasm and it is an honest-to-goodness disorder. I'll see if I can find it after work (if I'm not dead lol).
chjones may be correct about taking a "vacation" from Straterra. I was speaking of the Metadate CD that my grand-daughter has been on (and is still on). I stand corrected on that as I really do not know if that is possible with Straterra. Your doctor will definitely be able to tell you.Sueocon: Yes, she is very, very smart scholastically; however, without the meds, she is unable to focus, focus, focus!!! Very easily distracted, very chatty and very hyper. It takes awhile but the side effects will go away. They all go through them, just have patience. She has been on Medadate CD 2x's a day but only for school. She is a wonderful and obedient student as long as she's on the meds!! The other thing a lot of us on the board do (with the doctor's permission of course) is we do not medicate on weekends or school vacations. She is a little hyper on the weekends (what kid isn't???) and she gets a bit more sassy with her mouth (she'll be 11 in July), but nothing we can't cope with. The psychiatrist's feelings are she is what she is and we just have to deal with it the best we can, but his major concern is her ability to adjust, listen, focus and do well in school - that's his main concern. I think it's probably too early for you to do yet, but a few months down the road, with enough time for the meds to have kicked in, do discuss the same with your child's doctor(s). Bryanna was on 18 mgs. of Straterra also when she was on it. It did work great for her, as she also did better with a non-stimulant but has adjusted well to the Medadate after a month or so. Again, hang in there - we're all here for you when you need us (and vice-versa - it's a hell of a ride ain't it????).i thought Strattera was the one med that you shouldn't give 'med holidays' with!
Personally I wouldn't use a "med holiday" with a former anti-depressant like Stratterra until the MD said it was OK. I don't see the point as it doesn't acclimate like amphetamines. Makes no sense to me but I'm no doc either.
I'm not experienced much personally with tics (though I have a mild one that manifests when nervous or tired) but a recent study showed no increase in tics from no meds to meds. I would think maybe agitation could make them worse (it does with me) but maybe the medication doesn't make it happen the anxiety does. How they'd differentiate that is beyond me. But I do know they've stopped thinking that it aggravates tourettes.
They know that tics are caused by "sparks" of activity in the motor cortex and that it's a link between the reasoning brain and the core autonomic brain. I don't get a lot of what they explain but they do seem to have a hook on what is going on these days.
i think i have a major 'sloth' tic. i know that sounds weird - but when i get, what i call couch lock - i'm sure it isn't dissimilar to a tic.I know that there is a lot of bad press causing moms and dads to worry about medications and their children. Mostly it's hype but there are always exceptions.
Stratterra's biggest flaw is that its generally not of much use to the general ADHD population. It's typically used when the stimulants don't work or the worry of side effects (like the tics) is high. But they've done studies of ritalin and found little to worry about on the tic matter.
Stratterra is one I tried for a short time and found that it made me very tired and overly focused - to the point where I'd "zone" and not hear things going on around me. It was disconcerting.
Can those who have been on this one or parents of children that are on this one give me some info. I know this one has a ton of warnings but this is the first medicine my son's dr is prescribing because my son is prone to tics and he doesn't want to start him on a stimulant first. I hate the thought of medicating my son but the school is harrassing me and him (in their own manipulating ways), I don't know what else to do. I am tired of fighting them. If it wasn't for the school I wouldn't even consider the meds, I can handle my son just fine.
Strattera made our son worse. Sleepiness happens when coming down. School can't force meds and it's your choice to do or not. Some people use a stim/starttera.
Get this kid allergie/ sensativity tested. Can effecting behavior.