Donepezil may improve some autism symptoms.STANFORD, CALIF. -- A preliminary analysis of a randomized ran·dom·ize
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. , double-blind, placebo-controlled study of donepezil suggests that the Alzheimer's drug may slightly improve some neuropsychologic functions in children with autism autism (ô`tĭzəm), developmental disability resulting from a neurological disorder that affects the normal functioning of the brain. It is characterized by the abnormal development of communication skills, social skills, and reasoning. , Dr. Antonio Hardan said at a pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. update sponsored by Stanford University.
At the halfway point in a 20-week trial, improvements were seen in scores on the some, but not all, neurocognitive tests among 10 autistic autistic /au·tis·tic/ (aw-tis´tik) characterized by or pertaining to autism. children aged 7-17 years receiving the drug, compared with 10 receiving placebo.
Specifically, children somewhat improved their performance on tests aimed at measuring spatial executive functioning (the Design Fluency Test), selective attention (the Color-Word Interference Test) and the California Verbal Learning Test.
"We didn't see magic improvement or large improvements," said Dr. Hardan, director of the autism and developmental disabilities developmental disabilities (DD),
n.pl the pathologic conditions that have their origin in the embryology and growth and development of an individual. DDs usually appear clinically before 18 years of age. clinic at Lucile Packard Children's Hospital Lucile Packard Children's Hospital (LPCH) is a hospital located on the Stanford University campus in Palo Alto, California. It is staffed by over 650 physicians and 4,750 staff and volunteers. of Stanford (Calif.) University.
No improvement was seen on the Expressive One-Word Vocabulary Test vocabulary test A component of IQ tests in which a person is asked to define words of varying level of difficulty, and use them in context, which provides the examiner with a measure of the person's intellectual achievement and aptitude. See IQ test. , which measures language skills.
The trial is small and incomplete, and the results should be interpreted with caution, Dr. Hardan said, but "it opens up a whole group of medications to study."
The use of donepezil (Aricept) in autism was first studied by Dr. Hardan at the University of Pittsburgh in an open-label study of eight children, half of whom demonstrated improvement on the Aberrant Behavior Checklist and Clinical Global Impression Scale. Improvements were suggested in irritability and hyperactivity, but not in inappropriate speech, lethargy, or stereotypies, he reported (J. Child Adolesc. Psychopharmacol. 2002;12:237-41).
Another novel study of an existing drug in autism is ongoing at Indiana University, Indianapolis, where a broad-spectrum antibiotic once used to treat tuberculosis led to apparent improvement in social withdrawal in a pilot study. A randomized, double-blind study double-blind study,
n experimental technique in clinical research in which neither the researcher nor the patient knows whether the treatment administered is considered inactive (placebo) or active (medicinal). is currently underway, pitting d-cycloserine, a partial agonist of the N-methyl-D-Aspartate (NMDA NMDA
N-methyl-D-asparate ) glutamate receptor subtype (programming) subtype - If S is a subtype of T then an expression of type S may be used anywhere that one of type T can and an implicit type conversion will be applied to convert it to type T. , against placebo, Dr. Hardan said. Although these are small studies, it is encouraging to see research into existing drugs to determine whether they might be effective in treating children with autism spectrum disorders, he said.
It took 15 years for risperidone (Risperdal) to be approved for the treatment of autism-related irritability, noted Dr. Hardan, who published an early case study suggesting the drug's efficacy in 1996. Parents who must wait so long for drug approval feel they are "losing a lot of time," he said. "That's why they jump at any opportunity [to use a treatment, even one] that could be potentially hazardous for their child."
Dr. Hardan stressed that research must be driven by theories that make scientific sense, followed by proof-of-concept studies to see whether evidence exists that an agent may be helpful.
He pointed to "the [high] price of shortcuts See Win Shortcuts. ," such as secretin secretin /se·cre·tin/ (se-kre´tin) a hormone secreted by the duodenal and jejunal mucosa when acid chyme enters the intestine; it stimulates secretion of pancreatic juice and, to a lesser extent, bile and intestinal secretion. , hailed as a possible treatment based on one uncontrolled observational study that hinted it may have improved behavior in three children undergoing gastrointestinal procedures. No verification was made to determine whether the children actually met diagnostic criteria for autism, he noted. "Based on this, secretin was unfortunately the most studied medication in autism."
Fifteen randomized, double-blind studies eventually produced uniformly negative results. "You can't find anything consistent like that in medicine," he said.
The scientific community needs to "get realistic" when it comes to funding potentially beneficial treatments, he urged.
BY BETSY BATES
Los Angeles Bureau
RELATED ARTICLE: Is Autism on the Rise or Is the Diagnosis Expanding?
An apparent increase in the prevalence of autism and autistic spectrum disorders (ASDs) may be largely explained by differences in diagnosis, rather than true differences in the number of children with these conditions, Dr. Hardan suggested.
"Is there an increase in incidence versus an increase in recognition?" asked Dr. Hardan. Several observations point to the latter, he said.
Much of the increase in prevalence is among children with mild symptoms: children with high-functioning autism, those with Asperger's syndrome, and children with pervasive developmental disorder per·va·sive developmental disorder
Any of several disorders, such as autism and Asperger's syndrome, characterized by severe deficits in many areas of development, including social interaction and communication, or by the presence of repetitive, , not otherwise specified.
"Fifteen or 20 years ago when somebody was verbal, it was very unlikely people were going to consider this an autism spectrum disorder," he said. On the other end of the spectrum, children with moderate to severe mental retardation were given that diagnosis decades ago, whereas today many children receive the autism diagnosis.
Traditionally, autism spectrum disorders were exclusively made in school-age children. "Now people in their 20s and 30s who are struggling in daily living activities come to us and ask: 'Do I have an autism spectrum disorder?' Sometimes, some people do," said Dr. Hardan, but a diagnosis in adulthood would have been unthinkable years ago.
Another important contributor to the apparently increasingly prevalence of autism is simple misdiagnosis mis·di·ag·no·sis
n. pl. mis·di·ag·no·ses
An incorrect diagnosis.
mis·diag·nose , he maintained.
Children with ADHD Attention-Deficit/Hyperactivity Disorder (ADHD) Definition
Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder characterized by distractibility, hyperactivity, impulsive behaviors, and the inability to remain focused on tasks or often have social deficits, difficulties in developing peer relationships, and what Dr.
Hardan described as "poor coherence between visual and verbal behaviors." But what may resemble autism or an autistic spectrum disorder, often is not.
Children frequently referred to the clinic at Stanford who are misdiagnosed as autistic include those with severe anxiety symptoms, early onset personality disorders, and reactive attachment disorders. Children in the latter category, often adopted from overseas, have many features that could lead a clinician to mistakenly diagnose autism, including severe social deficits and sterotypical behaviors.
Methodological factors may also have contributed to apparent increases in autism prevalence, as depicted in a recent article, "The autism epidemic: fact or artifact?" (J. Am. Acad. Child Adolesc. Psychiatry 2007;46:721-30).