What Are We Treating With What?
September 13, 2007 by Kristina Chew, PhD
Filed under Health
Long Island pediatrician, allergist and immunologist, Dr. Marvin Boris, has been using two diabetes drugs, Actos and Avandia, to treat autistic children. As noted in today’s Newsday, researchers in the Journal of the American Medical Association have found that one of the medications, GlaxoSmithKline’s “controversial diabetes drug” Avandia, appears to raise patients’ risk of heart risk. The Wall Street Journal has the full story about the study on Avandia, and also another study on Actos, made by Takeda Pharmeceutical Company, which suggests that this medication is safer on the heart. Nonetheless, both medications carry the Food and Drug Administration’s toughest warning. Notes Newsday:
Dr. Sonal Singh, who led one of the studies reported today, said both drugs can cause bone fractures and fluid retention in the eyes, which potentially can lead to blindness.
Those studies “involve people who are prone to heart failure, and the extra water load they may retain from the Actos and Avandia may lead to heart failure and death,” Boris said yesterday.
He has noticed puffiness around the outside of the eyes of some children taking Actos, he said, but he has not looked inside their eyes to determine whether there is inner-eye swelling. He and his colleagues are prescribing the drug in what the FDA calls off-label usage, which is legal but usually occurs within the context of a clinical trial. Boris said he prescribes the drug because of its anti-inflammatory properties.
Michael Lincoff of the Cleveland Clinic has authored another study on Actos. Regarding giving an autistic child Actos not because the child has diabetes, but for anti-flammatory concerns, Lincoff says:
I would find it shocking………. If someone tests it in a clinical trial and it is being used as a result of evidence-based medicine, based on a body of research, but certainly not just not on gut instinct or a hypothesis.”
It is perhaps not so shocking that Dr. Boris is using Actos and Avandia to “treat” autistic children as Dr. Boris has been “involved” (since 2001) with the “Defeat Autism Now!” (DAN!) protocol, which views autism as a biomedical disorder to be treated by such alternative and experimental procedures as chelation. Dr. Boris is a member, along with some other DAN! doctors, of Autism Associates of New York whose webpage notes that it is “advancing in the treatments that may be help lead to a cure for Autism [sic].” A list of the various biomedical treatments that Dr. Boris’ center uses can be read here, including PPARS (Actos, Avandia):
Studies have shown that the FDA approved PPAR agonist, Actos, used to treat type 2 diabetes, is effective in treating many autoimmune diseases. These include rheumatoid arthritis, ulcerative colitis, Crohn’s Disease, Alzheimers, multiple sclerosis and psoriasis. In patients with secondary multiple sclerosis, daily treatment with Actos induced clinical improvement without adverse events. Peroxisome proliferator–activated receptors have been found to reduce inflammation of brain glial cells. Glial cells are inflamed in children with autism.
It is for similar reasons that PPAR agonists should be considered for use in children with ASD. In over 350 cases in our facility, there have been significant subjective responses in over 75 % of the children. These include, improved speech and language, focusing and socialization skills. We are currently participating in studies ongoing at the University of Illinois, Department of Neurology with both MS and ASD patients and their clinical responses to Actos.
Some of these statements from the Autism Associates of New York website need to be considered rather carefully. Glial cells are supportive, non-neuronal cells in the central nervous system. The Autism Associates of New York website simply asserts that “Glial cells are inflamed in children with autism” but (according to Rezaie, et al. Abstract from the 107th meeting of the British Neuropathological Society as published in Neuropathology and Applied Neurobiology, April, 2006) alteration of glial cells does not necessarily mean “neuroinflammation.” The alteration may have occurred for some other reason, such as hypoxic-ischemic injury (HII), which causes swelling in the brain; the swelling restricts the flow of blood-borne oxygen, glucose, and other nutrients (Autism Diva discusses the study further in a previous post). The assertation that “glial cells are inflamed” in autistic children is speculative; the evidence offered of treating children with anti-inflammatory diabetes drugs is described by the Autism Associates of New York website as “subjective”:
In over 350 cases in our facility, there have been significant subjective responses in over 75 % of the children. These include, improved speech and language, focusing and socialization skills.
Parents need more than speculative theories and “subjective” results when choosing an experimental treatment for autistic children, many of whom have communication difficulties that would impede their being able to accurately convey the effects of a treatment—and when a treatment is full of so many speculations and question marks, a lot more investigation is in order.
That treatment is shocking because of the apparent simplemindedness of it — in fact it seems so simpleminded that I suspect there’s more to the story. There’s a large pharma closet available for quenching inflammation, anyway, so one of my questions would be “even if this were a reasonable strategy, why use a new drug in children when old ones are available?”
Kristina, I’m getting an X=evil vibe to your use of “biomedical”, and I’m wondering what it comes from. It seems to me the problem with viewing autism or any other condition as “biomedical” is not that we can tinker (usuall hamfistedly) with the biology, but that if we can, individuals might come under intense social or legal pressure to do so whether they want to or not.
Personally, I don’t think there’s much sense in trying to separate identity from biology, however we might experience it day-to-day. Tinker with the chemistry, and sense of self can change dramatically. So I don’t think it makes a lot of sense to view autism as identity-based rather than biology-based; it seems to me they’re the same thing.
\”Parents need more than speculative theories and “subjective” results when choosing an experimental treatment for autistic children, many of whom have communication difficulties that would impeded their being able to accurately convey the effects of a treatment—and when a treatment is full of so many speculations and question marks, a lot more investigation is in order.\”
I find it hard to believe you are saying that, when your son is on meds too.
We try to investigate as much as we can!
I wonder if this 75 percent ‘claim’ is close to what Rimland claimed in his Secretin phase, which was later throughly disproven while others tried to reproduce the results and found placebo effect as likely an explanation, though normal development could have occured also.
“… here use this, you wont Appear to be autistic anymore, but then you might not see very well and may have heart complications later …” (Severe Sarcasm, of course.)
One does not give drugs willy nilly, just because you have an unproven theory of the particular disease process you are trying to treat.
That’s not how things are done. First you have to prove that a particular theory of disease is present in your disorder (i.e., autism is an inflammatory disease of glial cells). Then you might conduct clinical trials on patients with that disorder (i.e., autism).
You don’t just randomly try different drugs on patients because it “sounds good”. Especially drugs that have an FDA “Black Box” warning on them.
And you certainly don’t start widespread treatment of random patients without conducting some clinical studies.
Joe
Why not Joe? GPs and specialists prescribe off label all the time.
I believe one of the doctors whom you mention is reference in the article cited.
I’d suggest the “wisdom” gleamed by many at AA meetings. To whit, they’ve stopped drinking (and/or drugs), but smoke like chimneys after the meetings. A friend of mine (funny, I don’t know if I caught his last name), Big Tom, used to say ‘Deal with them in the order of they’re killing you.’
For a guy at an AA meeting, booze is killing him, the cigarettes are not. Moving from alcohol to tobacco to coffee to soda…we used to joke about it as “trading up.”
So about these colorful cocktails of chemical components, my first question would be which SPECIFIC attributes of autism do they address. In my speed read of the medical quotes (technical jargon puts me to sleep), I didn’t catch what the pill combo was going to do, other then “help” “cure” and/or “treat” — not specific enough for me.
The cure seems to exact a hight price (heart failure, eye-damage). That to me says, it’s a no-go!
If the cure is not worse than the disease, then the next level of consideration begins…mainly, is there another area of ‘treatment’ that might yield better benefits.
For instance, Captain Crash (my son Chris), has ADHD as well as autism; Romeo (my son Robbie) does not. Both are on the spectrum. Whatever helps Chris slow down enough to listen benefits all areas of development. Therefore, I’m not going to pursue something to reduces visual-stimming when the ADHD needs to be addressed. For Robbie, I’m not going to address “bolting off” when his No. 1 need is to unlatch from Mommy or Daddy and play independently. (How both these boys managed to stay on the spectrum escapes me! I guess that’s why they call it a spectrum! I’ll bang my forhead later.)
Once it’s clear this ‘treatment’ addresses the biggest need, then I’d look at efficacy. My opinion here is a bit like that of a gambler. If something is shown to be only 60% effective would I try it? How about 50%? 20%? Well, if it’s the greatest need, and it won’t make things worse, and we can afford it (in terms of time, energy, finances, etc), then yes I would.
How do I know that my boy(s) won’t be that 1 in 5? I can understand (readily) how people can flit from theory-to-theory, looking for that silver bullet. But, with many being ill-advised, and some downright dangerous, I think it does pay to curb the enthusiasm a bit. If you’re going to go with a low percentage approach, do so eyes-wide-open.
My hunny & I have been doing the ‘Feingold Program’ (it sure ain’t no diet!) for a year-and-a-half; we’re not extremely strict about it, but it does help. We find lots of benefits for everyone in the family for it. At this point, it’s pricey, but not much more difficult to do than “typical” grocery shopping. But, this is one of those “treatments” that doesn’t make things worse, addressed some key issues with Chris, and seemed to have anecdotal and analytical support to back it up. I find the anecdotal support to be important. I’d rather hear what worked for kids “a lot like Chris” and “a lot like Robbie” than to hear percentages that have nothing in common with my little people.
And, it’s hard to be analytical. Is the Feingold program “really” helping us? We think so; but, consider the near impossibility of getting an exact study on that. The kids will occassionally get non-Feingold foods. Chris get’s hyper; Tori get’s grumpy; Robbie gets cranky. I didn’t measure the amounts of food coloring they got; but, I know they had it, I see the results. hmmmm.
So, in summary, for any specific treatment, here’ Dr. Dan’s didactic diatribe: 1. Make sure it doesn’t make it worse; 2. Deal with them in the order they’re killing you; 3. Test the efficacy, if you can; 4. Compare notes with others.
Kristina, I think I’m going to owe you a cartridge of digital ink, if I keep typing like this!
Be Well, Do Good Work and Keep in Touch.
Dan
Why not Joe? GPs and specialists prescribe off label all the time.
While the term “off label” conjures up mental images of people using drugs for things totally unrelated to their original use, I have found that the majority of “off label” uses have been in one of two areas:
1) chemotherapy, where you are using drugs that have been tested and approved for one type of malignancy against another type of malignancy (for which there have been some studies, but not as many as would convince the FDA to give full approval for that indication, and
2) pediatric use of a drug that has a long history of use in adult patients for the same disorder. Most drug companies simply don’t want to go thru the expense and time of doing totally separate studies to prove a drugs use in pediatric patients.
I rarely come across any patients using drugs “off label” for any other uses than the above.
Joe
Hi Dan –
Very recently a study was announced showing that some common food additives do increase hyperactivity in some children.
It turns out your parental instinct was correct.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17825405&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- pD
We have had two different neurologists give us off label treatments, one to my ASD child, and one to my NT child. Both caused further complications but both doctors swore by their prescribed treatments. We see neither doctor now for obvious reasons.
Kristina, I notice that some of my recent comments have not made it onto the page. What’s up?
I did a little browsing on “off-label” use and found that, depending on the citation, country, and whether outpatient or hospital, anywhere from 40-90% of medicines prescribed for pediatric treatment is “off-label”.
At that point the question was, are there specific criteria for such use?
It appears to be
1. Backed by strong evidence of efficacy as based in published studies
2. Research setting–which I presume, is the clinical study or trials, with an IRB.
3. Extreme or urgent circumstances, such as life-threatening emergency where known treatments have proven ineffective.
Which category do these prescribing doctors working under un- or weakly evidenced hypothesis fall under?
(I’m not Orac or any of the other blogging physicians out there, so they will undoubtedly have a more sophisticated discussion of this and some correction to my simple-mind explanation). What troubles me at times is the feeling that in autism there is a “throw something at it an see if it sticks” quality to new drug or biomed treatments, especially in the hands of practitioners who seem to be doing “research” sans oversight and IRB and collect their grants in the form of out of pocket from parents.
amy, sorry about that. sometimes comments go into spam if there are too many URLs in them, or if a number of comments are quickly made my apologies—–it’s been one thing after another at my job. thanks for letting me know!
My son was in terrible shape at 15 months, all of the red flags for autism. We started actos and cod liver oil and he is a different kid. Now at 18 months he is a “normal” child, just doesn’t speak yet. Great eye contact, normal play, brings toys to show to us, friendly, etc. He was like a vegetable before the treatment. As a matter of fact, within 3 days of starting actos he stopped grinding his teeth. Prior to that the grinding was so loud and constant you could hear it across the house. The proof is in results for me.
My son had a period of teeth-grinding for some time—it comes and goes. Am I right that your did not receive a formal diagnosis of autism?