TORONTO – Some symptoms associated with autism–including hyperactivity, inattention, stereotypy, and aggression–can be improved with pharmacotherapy, Dr. Christopher McDougle said at the joint annual meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child and Adolescent Psychiatry.
But treating impaired social relatedness remains challenging, said Dr. McDougle of Indiana University, Indianapolis.
Nothing has been conclusively shown to be effective, although SSRIs, atypical antipsychotics, cholinergic agents, and glutamatergic agents have shown some promise, according to Dr. McDougle.
“We have seen some hints of effectiveness in some studies, and we're more optimistic about them,” he said. “They deserve further study.”
The psychostimulants have not fared well in autism, said Dr. McDougle, chairman and professor of psychiatry at the university. “There were substantial activating side effects in the early trials, and tolerability often remains an issue.”
He and his colleagues are about to publish results from a study of methylphenidate in children with pervasive developmental disorder (PDD) and hyperactivity. The 72 children received placebo and three doses of the drug in random order. Although 44 children responded to the drug, 13 (18%) dropped out because they couldn't tolerate at least two doses of it. Irritability was the most frequent cause of discontinuation.
“Right away, we got a sense tolerance was a concern, and the global response rate was much less than we see with typical children with ADHD,” Dr. McDougle said. Increased social withdrawal also occurred in some of the children. “Sometimes psychostimulants can lead to social withdrawal in ADHD, and at the highest doses in PDD, we saw a worsening of withdrawal.” Treating inattention in PDD is very difficult, Dr. McDougle said. “There are probably multiple causes for inattention. We really don't know what is going on,” he explained.
Unpublished data collected by Dr. David Posey, also of Indiana University, and his colleagues suggest that atomoxetine (Straterra) might be useful for inattention and hyperactivity in PDD.
Dr. Posey's open-label study included 16 drug-free children with PDD who received a mean dose of 1.2 mg/kg per day. The results were robust, Dr. McDougle said, with 75% of patients much or very much improved. However, two children (16%) were rated as much worse because of increased irritability. “The results are encouraging but preliminary,” Dr. McDougle said. “It's a possible alternative for those who can't tolerate a stimulant.”
Guanfacine (Tenex), generally used to treat high blood pressure, may be the best first step in pharmacotherapy for inattention, he said. “It might not help, but it won't make them worse. It may be the first use of these medications for the family, and you don't want to get off on the wrong foot by giving them a bad experience. But the best response is with a stimulant, if you can match up the right patient.”
Clonidine, an antihypertensive agent, has been shown effective in two small placebo-controlled studies. But that effectiveness may be partly attributable to the drug's sedative effects, he noted.
SSRIs are being studied for repetitive behavior, because they are often found in obsessive-compulsive disorder. Serotonin abnormalities are also found in autism, Dr. McDougle said.
Fluoxetine has been the most successful of these drugs, he said. A 2005 crossover placebo-controlled study of 39 children (aged 5–16 years) showed a significant reduction in repetitive behaviors with the drug. No significant effects on speech or social interaction were found, and no differences were found in side effects between the drug and placebo (Neuropsychopharmacology 2005;30:582–9). But parents should think carefully before medicating children just to reduce these behaviors, he said.
“You don't need to eliminate it just because it's present,” Dr. McDougle said. “Maybe it's OK to do these things if you have autism. Maybe you can just learn to leave it alone and appreciate the child for his uniqueness.”
Treating inattention in pervasive developmental disorder is very difficult. DR. MCDOUGLE