NEW YORK – The body of data for using newer pharmacotherapeutic agents to treat autistic symptoms is struggling to keep up with the use of such drugs in practice, Lawrence Scahill, Ph.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
“An evidence-based discussion of autism is relatively brief, because we don't have a lot of evidence, unfortunately,” said Dr. Scahill, director of the research unit on pediatric psychopharmacology at the Yale Child Study Center, New Haven, Conn.
“We don't have great medications for the core symptoms of autism,” such as delay or disinterest in social interaction, repetitive behavior and restricted interests, and impaired communication. But some medications have proven to be useful in treating target symptoms, such as hyperactivity, tantrums, aggression, self-injury, and anxiety, he added.
In a survey of medication patterns in patients with autism or pervasive developmental disorder (PDD) in North Carolina, the use of any medication to treat the conditions rose from 31% in 1992–1993 to 45% in 2001, even though data do not exist to support the use of many medications, Dr. Scahill noted (J. Child Adolesc. Psychopharmacol. 2005;15:116–26).
The use of several classes of drugs rose noticeably during that period, including antipsychotics (from 12% to 17%), antidepressants (from 6% to 21%), and stimulants (from 7% to 14%). For antipsychotics and antidepressants, these changes reflect switches to atypicals and SSRIs, said Dr. Scahill, who disclosed that he serves as a consultant for Janssen Pharmaceutica N.V., which manufactures risperidone (Risperdal), and Pfizer Inc., which is the manufacturer of fluoxetine.
SSRIs for Repetitive Behavior, Anxiety
SSRIs such as fluoxetine have been used in PDD to treat repetitive behavior, anxiety, and aggression, as well as to improve socialization, Dr. Scahill said.
Liquid fluoxetine proved to be more effective in treating repetitive behaviors than placebo in a randomized, double-blind, crossover study of 39 children and adolescents with autistic spectrum disorders.
In the first phase of the trial, patients who received fluoxetine improved their scores on a clinician-rated instrument focused on repetitive behavior (the Children's Yale-Brown Obsessive Compulsive Scale-PDD) by 10% (12.8 to 11.6), compared with placebo patients who improved by 4% (from 13.4 to 12.9). The second phase of the study, in which the patients switched treatments, yielded similar results.
Adverse events occurred at a rate similar to that of placebo. The patients received an average dose of fluoxetine of 10 mg/day, beginning with 2.5 mg/day for the first week.
By increasing the dose slowly, the investigators avoided SSRI-induced activation, which may include insomnia and increased motor activity, talkativeness, impulsive behavior, or aggression, Dr. Scahill said.
“In terms of benefit, if you're aiming [SSRIs] at repetitive behavior, I don't say 'Don't do it,' but don't expect big effects,” he said.
Aggression, Tantrums, Self-Injury
Risperidone is the atypical antipsychotic that has been studied most extensively in PDD. Open and controlled trials with risperidone have involved 223 patients with PDD. The Food and Drug Administration previously declared risperidone as nonapprovable for the treatment of autism in children, but it is now being submitted for approval for the treatment of tantrums, aggression, and self-injury, Dr. Scahill said.
In an 8-week, randomized, double-blind trial, risperidone significantly reduced aggressive behavior, tantrums, and self-injurious behavior by 57% in 49 children, compared with 14% in 52 children on placebo, according to the parent-rated irritability subscale of the Aberrant Behavior Checklist. Clinician ratings yielded similar results. The patients averaged 1.8 mg per day (N. Engl. J. Med. 2002;347:314–21).
During a 4-month open-label extension of the study for 63 responders to risperidone, irritability scores did not worsen, and patients did not require more risperidone to maintain their response (Am. J. Psychiatry 2005;162:1361–9). These responders gained an average of 5.6 kg during a total of 6 months of treatment with risperidone (Am. J. Psychiatry 2004;161:1125–7).
In a 2-month, randomized, double-blind discontinuation of risperidone, patients who continued to receive risperidone had a significantly lower rate of relapse (2 of 16) than did patients who gradually replaced risperidone with placebo (10 of 16).
Even though “we know that hyperactivity is a very common problem” in children and adolescents with PDD, “the evidence to support the use of methylphenidate in this population is frightfully little,” Dr. Scahill said.
Until recently, methylphenidate had been studied in only two trials of 10 children with PDD and ADHD. On the Conners Hyperactivity Index, teachers reported 11% improvement at a dose of 10–20 mg twice daily (J. Autism Dev. Disord. 1995;25:283–94), 32% improvement at 0.3 mg/kg per dose, and 47% improvement at 0.6 mg/kg (J. Am. Acad. Child Adolesc. Psychiatry 1999;38:805–12).