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Posted by on Nov 7, 2008 in Ethics, Neuropsychiatry, Toxicology

Evidence for Chelation in Autism: Slim to None (Okay, Really None)

Evidence for Chelation in Autism: Slim to None (Okay, Really None)

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In a show of institutional wisdom, the NIMH recently scrapped the idea of studying chelation therapy in autistic children. The study would have been the first well-controlled trial in autistic children of the treatment, which has been used largely on the QT and based on the unfounded idea that autism is caused by environmental mercury poisoning.

Published effects of chelation in autistic individuals (according to a PubMed search) are confined to case reports and letterswhich, in some instances, reveal serious adverse effects, including death, of the therapy. A recent case report from The Netherlands described the development of Stevens-Johnson syndrome with oral DMPS therapy (eg, Unithiol, Dimaval, Mercuval) in an asymptomatic 11-year-old boy exposed to mercury vapor.

In 2005, a 5-year-old autistic British boy died after undergoing chelation therapy (Na2EDTA or edatate disodium 990 mg) by IV push in the office of US physician Roy Kerry. The cause of death was cardiac death due to hypocalcemia. (Addendum: This case was presented online last month in Clinical Toxicology.) Also that year, a 2-year-old girl with lead poisoning died of chelation-induced hypocalcemia, due to the unintentional administration of Na2EDTA (Endrate; Hospira) instead of the ordered CaNa2EDTA (edatate calcium disodium or Calcium Disodium Versenate; 3M) in a Texas hospital. In 2003, a 53-year-old woman in Oregon died of cardiac arrest due to hypocalcemia after receiving an unspecified EDTA compound, 1500 mg, by IV push. The chelator, prescribed by a naturopathic physician, was intended to remove heavy metals. (These deaths were also reported in the MMWR.)

According to Brown et al (2006), CaNa2EDTA (which is a nonspecific metal chelator) and another chelator, succimer (DMSA or Chemet; Ovation), are unlikely causes of hypocalcemia. Na2EDTA, however, “should never be used for treating lead or other heavy metal poisoning in children because it induces hypocalcemia, which can lead to tetany and death.” According to the prescribing information, Na2EDTA is “indicated in selected patients for the emergency treatment of hypercalcemia and for the control of ventricular arrhythmias associated with digitalis toxicity.” Earlier this year, the FDA issued a public health advisory regarding confusion between Na2EDTA and CaNa2EDTA and recommended the use of newer alternatives for Na2EDTA indications.

In the 2007 case series of Mark and David Geier (which shows up in a PubMed search for trials or case reports, using the words “autism” and “chelation”), DMSA or DMPS was administered to 8 children (at 3-14 years of age), most often as “provocation” or “challenge” doses. The amounts of DMSA or DMPS administered in these cases are not specified. Three children (at 3, 5, and 5 years of age) received “therapy” or a “treatment course” with DMSA or DMPS. Dosages prescribed and the durations of therapy in these cases are also not specified by the Geiers. Chelation was most often administered orally; although a 5-year-old child received a “provocation dose” of DMSA by suppository, and a 3-year-old child and a 5-year-old child received DMPS “therapy” transdermally.

Subject

Chelation Therapy

Route of Administration

1

@ 5 years

“Provocation dose” of DMPS

Oral

2

@ 5 years

“Provocation dose” of DMSA

“Provocation dose” of DMPS

Suppository

Oral

3

@ 4 years

@ 5 years

DMSA “challenge”

DMSA “therapy”

Oral

Not described

4

@ 3 years

@ 5 years

“Provocation” DMSA

DMPS “therapy”

Oral

Transdermal

5

@ 5 years
@ 6 years

“Provocation dose” of DMSA

“Provocation dose” of DMSA

Oral

Oral

6

@ 6 years

“Provocation dose” of DMSA

Oral

7

@ 14 years

DMPS “challenge”

Oral

8

@ 3 years

“Treatment course” of DMSA
“Treatment course” of DMPS

Oral
Transdermal

According to the Chemet (DMSA or succimer) prescribing information, the drug “is indicated for the treatment of lead poisoning in pediatric patients with blood lead levels above 45 μg/dL.” So-called provocation or challenge doses of the drug are not described. (A PubMed search reveals articles about the provocative use of chelating agents in the setting of lead exposure onlyeg, Lee et al, 1995.) The drug is administered orally and on the basis of the child’s weight. A course of treatment lasts 19 days and may be repeated, depending on the blood concentration of lead. For children who cannot swallow capsules, the contents may be sprinkled on food. Although there is a lot of online discussion among autism groups about the use of DMSA as a suppository, the manufacturer evidently does not offer a suppository formulation or recommend suppository administration of the agent.

The branded forms of DMPS do not appear to have been reviewed or approved for use in the United States by the FDA. A 2004 letter from the company Heyltex (whose parent company in Germany makes Dimaval) reported cases of skin reactions to pharmacy-compounded versions of the drug for transdermal administration. Most important, the company indicated that it was unaware of any clinical data demonstrating the efficacy or safety of transdermal DMPS and recommended that the drug only be compounded for oral or injectable administration. (The absorption of transdermal DMPS has also been questioned by Orac.*) It is unclear how DMPS is obtained by US pharmacies for compounding; however, the drug may be freely available in Germany without a prescription, given its longstanding status there. (Addendum: In a 1999 issue of the Federal Register, the FDA proposed that DMPS be considered a bulk drug substance that may be used in pharmacy compounding, although the substance is not an FDA-approved drug. According to Anderson and Aaseth (2002),

DMPS is registered in Germany for treatment of mercury intoxication; however, it is not approved in the United States, so unless special permission is given by the US Food and Drug Administration, it is not lawful for physicians to use it in the United States, nor is it lawful for pharmacies to compound it. Still, DMPS is being illegally used by members of the alternative health industry to treat people allegedly suffering from mercury intoxication…)

There is no specific indication by the Geiers that treatment courses with chelation, 2 of which were administered transdermally (DMPS) and 1 of which was administered by an unidentified route (DMSA), directly affected clinical symptoms in their autistic subjects.

DMPS = 2,3-dimercapto-1-propanesulfonic acid; DMSA = dimercaptosuccinic acid; EDTA = ethylenediamine tetraacetic acid.

* The question of the absorption (and the consequent efficacy) of transdermal DMPS is especially important, because the Geiers reported “significantly elevated mercury levels” in the hair of a child who had received transdermal DMPS therapy and “significant concentrations of mercury” in the fecal sample of another child who had received transdermal DMPS therapy, suggesting that transdermal chelation promoted the excretion of mercury.

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.