Multisite, double-blind, placebo-controlled trial of porcine secretin in autism.

OBJECTIVE: To examine the efficacy of intravenous porcine secretin for the treatment of autistic disorder. METHOD: Randomized, double-blind, placebo-controlled, crossover design. Fifty-six subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Observation Schedule (ADOS) and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects. RESULTS: For the primary efficacy analysis, change of ADOS social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-0.8 +/- 2.9) and secretin groups (-0.6 +/- 1.4; t54 = 0.346, p < .73). The other measures showed no treatment effect for secretin compared with placebo. CONCLUSION: There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial.

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Utility of the Gilliam Autism Rating Scale in research and clinical populations.

The Gilliam Autism Rating Scale (GARS) was developed as a relatively easy, inexpensive aid in the surveillance and diagnosis of autism. This study examined the validity of the GARS when used with a sample of 119 children with strict DSM-IV diagnoses of autism, ascertained from both clinical and research settings. The GARS consistently underestimated the likelihood that autistic children in this sample would be classified as having autism. The sample mean for the Autism Quotient, a hypothesized index of the likelihood of having autism, was 90.10, significantly below the reference mean of 100. Diagnostic classification according to criteria specified by the GARS resulted in a sensitivity of only .48. Limitations of rating scales in general and of the GARS specifically are discussed. It is recommended that clinicians and researchers using or considering using the GARS for autism diagnosis or ratings of autism severity recognize the need for further research regarding its use.

Word familiarity and frequency in visual and auditory word recognition.

Four experiments investigate printed word frequency and subjective rated familiarity. Words of varied printed frequency and subjective familiarity were presented. A reaction time advantage for high-familiarity and high-frequency words was found in visual (Experiment 1) and auditory (Experiment 2) lexical decision. In Experiments 3 and 4, a cued naming task elicited a naming response after a specified delay after presentation. In Experiment 3, naming of visual words showed a frequency effect with no naming delay. The frequency effect diminished at longer delay intervals. Naming times for auditorily presented words (Experiment 4) showed no frequency effect at any delay. Both naming experiments showed familiarity effects. The relevance of these results are discussed in terms of the role of printed frequency for theories of lexical access, task- and modality-specific effects, and the nature of subjective familiarity.