“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, Sikich 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.