Therapies for Children With Autism Spectrum Disorders

Table 22. Outcomes of RCTs of other medical interventions for the treatment of ASDs (continued)
Author, year, Mean age, Mean IQ ±
Key outcomes
country
Groups, N
enrollment/N final
Study quality
years ± SD SD
King et al. 251
G1: 7 (SD NR, Overall= >35 • Proportion of responders (reduction of at least 25%
2001, US
range=5-11)
in subscale scores for ABC-C-irritability &/or
G2: 7 (range=5-
hyperactivity) in treatment group (9, 47%) was
G1: amantadine, 15 )
higher than in the placebo group (7, 37%), but was
43(total)/19
G2: placebo,
43(total)/20
not statistically significant (p=0.511).
Quality: Fair
ABC=Aberrant Behavior Checklist; ATEC=Autism Treatment Evaluation Checklist; DH=donepezil hydrochloride;
EOWPVT=Gardner’s Expressive One Word Picture Vocabulary Test; IGOH=oral human immunoglobulin; MGIS=Modified
Global Impression Scale; ROWPVT=Gardner’s Receptive One Word Picture Vocabulary Test; SD=standard deviation
Risperidone plus piracetem was associated with more improvement on the ABC-C than
risperidone alone in one RCT of 40 children ages 3–11, with similar incidence of extrapyramidal
symptoms, and other adverse events. 252
A 10-week RCT of pentoxifylline added to risperidone compared with placebo plus
risperidone included 40 children between the ages of 4 and 12 years. 253 Scores on the ABC-C
lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate
speech subscales were significantly better for the pentoxifylline group compared with placebo
(P ≤ 0.0001). Scores on the Extrapyramidal Symptoms Rating Scale and frequency of side
effects did not differ between groups. Adverse events reported in either group included GI
symptoms, restlessness, drowsiness, weight gain/increased appetite, and fatigue.
In one RCT at 12 US centers, oral human immunoglobulin showed no effect on
gastrointestinal symptoms, ABC-C scores or clinical rated global impression scores, and there
was a significant effect in favor of placebo on the parent-rated global impression scores. 64
Hyperbaric therapy was also studied in one RCT and showed some benefit. The study was
conducted at six US clinics and included 62 children ages 2-7 years with ASDs. 254 Participants
were randomized to 40 hourly sessions over 4 weeks of either hyperbaric therapy (room pressure
1.3 atmospheres (atm); 24 percent oxygen) or slightly pressurized room air (1.03 atm; 21percent
oxygen). Both groups had significant improvement in clinician-rated CGI after treatment as
compared with baseline; however, while eighty percent of children in the hyperbaric group
improved on this outcome, only 38 percent of control participants improved.
The investigators reported no significant difference in ABC-C or parent-rated CGI between
groups at outcome. There were significant changes in Autism Treatment Evaluation Scale total
scores and some subscales for both groups compared with baseline; significant between-group
differences in the amount of change were observed on the sensory/cognitive awareness subscale
only. No episodes of seizure or barotrauma occurred during the sessions; other adverse events
were rare and included two skin-related events, worsening of asthma, and GI symptoms.
Two studies explored the use of cholinesterase inhibitors in ASDs, both conducted at a
specialty clinic. The study of donepezil hydrochloride included 43 children ages 2-10 years with
ASDs. 257 Children were randomized to six weeks of donepezil or placebo, followed by a sixweek
open label continuation. Both groups showed significant improvements on the Childhood
Autism Rating Scale measure, but there were no between group differences. Nine children
76