Study Finds Succimer Ineffective for Removing Mercury as Autism Treatment

Succimer, a drug used for treating lead poisoning, does not effectively remove mercury from the body, according to researchers. Some families have turned to succimer as an alternative therapy for treating autism.

“Succimer is effective for treating children with lead poisoning, but it does not work very well for mercury,” said Walter Rogan, M.D., head of the Pediatric Epidemiology Group at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and an author on the paper that appears online in the Journal of Pediatrics.

“Although it is not approved by the Food and Drug Administration to reduce mercury, succimer is reportedly being used for conditions like autism, in the belief that these conditions are caused, in part, by mercury poisoning,” Rogan stated. “Our new data offers little support for this practice.”

Although researchers found that succimer lowered blood concentrations of mercury after one week, continued therapy for five months only slowed the rate at which the children accumulated mercury. The safety of higher doses and longer courses of treatment has not been studied.

Most mercury exposure in the United States is from methylmercury, found in foods such as certain fish. Thimerosal, a preservative once more commonly used in vaccines, contains another form of mercury, called ethylmercury.

To conduct the study, the researchers used samples and data from an earlier clinical trial, led by NIEHS, called the Treatment of Lead-exposed Children (TLC) trial. In the TLC study, succimer lowered blood lead in 2-year-old children with moderate to high blood lead concentrations.

Using blood samples from 767 children who participated in the TLC trial, the researchers measured mercury concentration in the toddlers’ blood samples collected before treatment began, one week after beginning treatment with succimer or placebo, and then again after three month-long courses of treatment. Mercury concentrations were similar in all children before treatment. Concentrations eventually increased in both groups, but more slowly in the children given succimer. Succimer had produced a 42 percent difference in blood lead, but only an 18 percent difference in blood mercury.

“Although succimer may slow the increase in blood mercury concentrations, such small changes seem unlikely to produce any clinical benefit,” Rogan said. He and his colleagues had reported in an earlier paper that succimer has few adverse side effects, mostly rashes, and an unexplained increase in injuries in children given succimer rather than placebo.

The subjects of the study did not have unusually high blood mercury concentrations for African-American children and the study did not investigate where the mercury in the children came from.

“This research fills a gap in the scientific literature that could not be addressed any other way. We were fortunate to have samples already collected from toddlers who had been treated with succimer for lead poisoning allowing us to help answer this important question,” said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program.

Reference: Cao Y, Chen A, Jones RL, Radcliffe J, Dietrich KN, Caldwell KL, et al. 2010. Efficacy of Succimer Chelation of Mercury at Background Exposures in Toddlers: A Randomized Trial. J Pediatr. Epub ahead of print. DOI:10.1016/j.jpeds.2010.08.036.

Source: National Institutes of Health (NIH), October 22, 2010

Autism Drug Citalopram Is Ineffective, Says Study

A drug commonly given to autistic children to reduce repetitive behaviors is ineffective compared to placebo and, in some children, may actually increase repetitive behaviors, the largest study of autistic children to date has found.

“What we found, much to our surprise, is that there was no significant difference in positive response between kids treated with citalopram and kids who received the placebo. And the kids treated with citalopram tended to have more side effects,” said Linmarie Sikich, M.D., a co-author of the study and associate professor of psychiatry in the University of North Carolina at Chapel Hill School of Medicine.

“I cannot emphasize this enough: This was not at all what we expected to see,” Sikich said.

Results of the study, a randomized controlled clinical trial of the drug citalopram, are published in the June 29, 2009 issue of Archives of General Psychiatry. It was funded by the National Institutes of Health and took place at six academic medical centers across the country. Principal investigator and lead author of the study is Bryan H. King, M.D., who began the study at Dartmouth and continued to oversee it there after he moved to the University of Washington, where he is currently director of psychiatry and behavioral medicine at Seattle Children’s Hospital.

Citalopram, which is sold under the brand name Celexa, is one of a class of antidepressant drugs called selective serotonin reuptake inhibitors, or SSRIs. SSRIs are the most frequently used medications for children with autism. They are also used to treat depression, anxiety and obsessive compulsive disorder in both adults and children. Prior to this study there was very little scientific evidence to support the use of SSRIs in autistic children, but some preliminary studies showed promising results for citalopram, Sikich said.

Hypothesizing that citalopram would improve the overall functioning of autistic children and adolescents by reducing repetitive behavior, Sikich and colleagues recruited 149 children ages 5 to 17 to take part in the 12-week trial. Seventy-three received daily doses of liquid citalopram while 76 received daily doses of liquid placebo. Researchers measured the children’s’ response to treatment using the Clinical Global Impression-Improvement scale (CGI-I). They also recorded measures of repetitive behavior and side effects.

At the end of the trial, some children in both groups showed a positive response. However, there was no significant difference between the groups: the positive response in the citalopram group was 32.9 percent versus 34.2 percent in the placebo group. In addition, children in the citalopram group were significantly more likely to experience adverse side effects such as increased energy level, impulsiveness, decreased concentration, hyperactivity, increased repetitive movements and behaviors, diarrhea, insomnia, and dry itchy skin.

The researchers concluded that citalopram “is not an effective treatment” for autistic children with repetitive behaviors. In addition, they wrote, this trial shows that the use of SSRIs in autistic children “is not without risk” and “at present there is insufficient research evidence to merit a clear recommendation regarding the use of SSRIs as a class” for the treatment of repetitive behavior in children with autism spectrum disorders.

“The obvious short term message is, this treatment didn’t work. And that surprised us a great deal,” Sikich says. “But the really important take-home message is that we have to do large, scientifically-sound comparative studies like this to really know whether a specific treatment works and is safe. Simply relying on doctors’ and families’ impressions often leads us to use medications that really don’t work and may do more harm than good” says Sikich.

Safe and effective medication and behavioral treatments are desperately needed to help children with autism realize their potentials and keep from harming themselves or others, Sickish says.

“Well-done studies, using methods like the ones in this study, have shown that another drug, risperidone, is useful in reducing irritability and aggression in children with autism,” she says. “Thus, this study shouldn’t be interpreted as saying all medications don’t help people with autism and are harmful. Instead it says that citalopram doesn’t help most children with autism and is harmful to some children. Clearly we need more research to develop and test other interventions for this important problem.”

People with autism are severely impaired by the disorder and experience major problems with highly repetitive behaviors, often including self-injurious behaviors, communicating and interacting appropriately with others. Frequently the repetitive behaviors keep children with autism from learning in school or participating in age appropriate activities. When it is time to stop the repetitive behavior and begin a new, functional activity, many children with autism become distraught and aggressive. These repetitive behaviors also contribute to the difficulties that make it hard for most people with autism to live independently or work as adults, Sikich says.

In addition to UNC, academic medical centers taking part in the study were Mt. Sinai School of Medicine, North Shore-Long Island Jewish Health System, Dartmouth, UCLA and Yale University.

The study was conducted as part of the NIH-sponsored Studies to Advance Autism Research and Treatment network.

Source: University of North Carolina at Chapel Hill School of Medicine , May 28, 2009

Differing Brain Connections May Cause Autism’s Social Impairment

The brains of adults with autism may be "wired" differently from people without the disorder, and this abnormal pattern of connectivity may be responsible for the social impairments that are characteristic of autism.

Using functional magnetic resonance imaging, a team of researchers affiliated with the University of Washington’s Autism Center found that the most severely socially impaired subjects in the study exhibited the most abnormal pattern of connectivity among a network of brain regions involved in face processing.

"This study shows that these brain regions are failing to work together efficiently," said Natalia Kleinhans, a research assistant professor of radiology and lead author of the paper published in the journal Brain. "Our work seems to indicate that the brain pathways of people with autism are not completely disconnected, but they are not as strong as in people without autism."

The study is the first to look at brain connectivity and social impairment, and focused on how the brain processes information about faces. Deficits in face processing are one of the earliest characteristics to emerge in people with autism.

The research team led by Elizabeth Aylward, a UW professor of radiology, examined connectivity in the limbic system, or the network of brain regions that are involved with processing social and emotional information.

Participants in the study included 19 high-functioning adults with autism who had IQs of at least 85. They ranged in age from 18 to 44 and were compared with an age- and intelligence-matched sample of 21 typically developed adults.

The group with autism spectrum disorder included eight individuals diagnosed with autism, nine with Asperger’s syndrome and two diagnosed with pervasive developmental disorder not otherwise specified. The level of social impairment for each autistic participant was drawn from records of clinical observations and diagnoses that confirmed that each had autism.

Each participant had his or her brain scanned while looking at pictures of faces or houses. Participants were shown four series of 12 pictures of faces and a similar number of series showing houses. Each individual picture was seen for three seconds. Occasionally the same face or house picture was repeated, and participants were told to press a button when this occurred.

There was no significant difference on the two groups’ performance, because the task was so basic, said Todd Richards, a professor of radiology and co-author of the paper. "Differences might have shown up if they had been asked to do something more complicated."

However, the two groups exhibited different patterns of brain activity. The researchers focused on the fusiform face area of the brain, a region that is involved in face identification. Compared to the participants with autism, the typically developing adults showed significantly more connectivity between the fusiform face area and two other brain regions, the left amygdala and the posterior cingulate. In addition, autistic participants who had the largest social impairment showed the lowest level of connectivity between the right fusiform face area and the left amygdala and increased connectivity between the right fusiform face area and the right inferior frontal gyrus.

"This study shows that the brains of people with autism are not working as cohesively as those of people without autism when they are looking at faces and processing information about them," said Kleinhans.

Source: University of Washington, June 12, 2008