Alzheimer’s Drug Shows Promise As Treatment for Autism

One of the most heartbreaking aspects of autism, parents of children with the disorder often say, is how their child often started off developing normally in life, but then around the age of a year and a half began to withdraw from them and the world, into an inner realm of self-absorption and silence. As one mother recalled with anguish, “He became totally nonverbal, zoned out. It was as if he was no longer even in the solar system.”

Thus, if a medication were identified that could improve speech in youngsters with autism, it would be a remarkable medical advance.

Such a medication may possibly have been found. It is donepezil—one of several drugs on the market for countering symptoms in the early stages of Alzheimer’s disease.

The discovery comes from Michael Chez, M.D., a child neurologist and assistant professor of neurology at Rush Medical School in Lake Bluff, Ill., and coworkers. He reported the group’s findings at a poster session at the annual meeting of the American Neurological Association in Chicago in October.

The idea for this study, Chez explained in an interview with Psychiatric News, came after he had visited conferences where he interacted with scientists studying Alzheimer’s disease. “It came to me,” he said, “that if we tried one of the Alzheimer’s drugs on children with autism, it might sort of kick-start some of the dormant areas [of the brain] that maybe had never developed due to the fact that there may have been a lack of developmental input early on, since many of these kids regress between 18 months and 3 years of age.”

So in 1999 he and his coworkers gave donepezil to some children with autism in a pilot study and found an improvement in speech. That led, in 2000, to a placebo-controlled study.

They enrolled 51 children with autism into this study. All were comparable in their speech disabilities. Half received donepezil and half a placebo during a six-week period. Then the placebo group received donepezil for another six weeks. Neither families nor investigators knew when the subjects were getting donepezil or a placebo.

At the end of both the six-week and 12-week periods, subjects’ receptive speech (verbal comprehension) and expressive speech (ability to express through words and pictures) were assessed and compared. That is, the speech of the treatment group was compared with that of the placebo group, and the speech of the placebo group was compared with when it was getting a placebo and when it was getting donepezil. In the first case, the subjects who had gotten donepezil were found to be significantly better at both receptive and expressive speech than those who had not received the drug. In the second case, subjects who did not get donepezil initially but who later did proved to be significantly better at both receptive and expressive speech after taking donepezil.

“We are now planning to publish our findings,” Chez said, “and we were invited by one of the major neurology journals to submit it.

“I believe that Michael Chez’s Aricept [donepezil] study in autism is promising, conceptually intriguing, and a worthwhile first step in addressing the language deficit domain, which has not been improved with other agents to date,” Eric Hollander, M.D., a professor of psychiatry at Mount Sinai School of Medicine in New York City, told Psychiatric News. “Of course, his initial study needs to be replicated with larger, well-designed placebo-controlled trials that utilize validated outcome measures.”

“The study is encouraging and intriguing,” Steve Roach, M.D., a child neurologist at the University of Texas Southwestern Medical Center in Dallas, said in an interview with Psychiatric News. “In fact, for these kids, this is actually one of the more encouraging studies I’ve seen. . . .You know, if this pans out, this is something that is going to help the kids.”

An aspect of the study that gives it credibility, Roach believes, is that the children who seemed to improve from donepezil were mild to moderately affected, not severely affected.

“This sounds intuitively right,” he said, because donepezil is a symptomatic treatment. That is, the drug does not reverse the damage caused by the disease process or halt the patient’s deterioration; instead, it improves the patient’s functioning for a time.

"So, if you had a crystal ball that said, O.K., this drug works, you would actually predict that the children who had some reasonable function to begin with might respond, just as you would predict, if you used it on someone in the very late stages of Alzheimer’s, that it really wouldn’t do any good. In other words, you are improving existing function, not conjuring something up like a rabbit out of a hat. To me, that was very positive.”

The study was funded by the Dr. Michael G. Chez Fund for Epilepsy and Autism Research. Pfizer Pharmaceuticals, the maker of donepezil, gave a grant to the fund after the study was over and did not influence its design or outcome, Chez said. ▪