There is only one controlled study supporting the efficacy of HBO therapy for autism. However, another randomized, double-blind, controlled trial did not support the efficacy of HBO therapy for the treatment of autism [21
]. There are several points regarding that study [21
]. First, 12 out of the 46 participants withdrew from the study. Therefore, the number of the patients in each group was limited; however, it is not clear whether the negative results can be attributed to the small sample size. In addition, the control group received free airflow through the chamber at ambient pressure. It is a debate whether this is really a placebo intervention. It should be noted that the participants in both groups showed improvement over time. Of course, it does not mean that other options for HBO therapy, such as other doses, are not effective. Furthermore, both groups were administered intensive ABA intervention during this study. One explanation for the lack of efficacy is that HBO therapy does not add significant therapeutic effects to ABA; therefore, It cannot be interpreted that HBO therapy is ineffective. However, it is not clear if direct observation has enough reliability and validity to be considered as an outcome measure.
The other randomized, double-blind, placebo-controlled trial reported that some children with autism can benefit from HBO therapy [22
]. However, there are some concerns about that study. The measures used in that study were Clinical Global Impression scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC). In addition, an intention-to-treat approach was used for statistical analysis. One of the measures used in that study was CGI. It is expected that clinicians rate CGI to show the degree of changes. Although, CGI is not scored at baseline, both parents and physician scored CGI at baseline in that study. Moreover, the improvement of overall functioning, receptive language, social interaction, and eye contact were assessed according to CGI. Meanwhile, CGI is used in order to show the overall changes. Of course, the validity and reliability of CGI for assessment of overall functioning, receptive language, social interaction, and eye contact in autism should be investigated.
Of course, another scale was also used in that study. As the results showed, no difference was observed between the two groups regarding the ABC total score and subscale scores (p = ns). However, there was a trend for a significant difference between the two groups regarding the irritability subscale score (p = 0.0976).
Autism Treatment Evaluation Checklist (ATEC) Scale was also administered. Sensory/cognitive awareness in the treatment group improved more than that of control group. However, 10 patients in the treatment group and 8 patients in the control group were not assessed at baseline by this scale; therefore, the data for 44 patients were gathered. Nevertheless, it is not clear whether it has any impact on the results of this study. In addition, it is not clear whether the statistical differences are due to the alpha inflation.
There are some other possible explanations for the difference between these two studies' findings. a) The patients' diagnostic characteristics of these two trials are not similar. While one of them included the patients with autism spectrum disorders [21
], the other study included the patients with autism [22
]. In addition, the children with PDD-NOS, Asperger syndrome, and fragile X syndrome were excluded from the study [22
]. b) One study supported the efficacy of HBO therapy according to CGI as an outcome measure [22
], while the other study did not find these results using CGI. c) Only one of these two studies reported that the patients demographic characteristics (age and gender ratio) and baseline severity were not different between the treatment group and control group [22
]. d) while one study included children aged 2 to 14 years old [21
], the other study included those between 2 and 7 years old [22
]. e) One study was a multicenter study [22
], while the other study was conducted in one center [21
]. It needs to be mentioned that the age of the children, autism severity, and the degree of improvement were not different between these six centers [22
]. f) While the outcomes were assessed by the parents or primary caretakers and the treating physician [22
], the trained assessors, who were blind to group assignment, and evaluated the outcome for another trial [22
]. g) The assessment of blinding was conducted for one study [21
], while it was not performed for the other one [21
]. h) One study provided about 5 treatments per week [21
], while the other study provided 10 treatments per week [22
This systematic review has a limitation because only one author reviewed the articles and scored the quality of the experimental studies.
In conclusion, the results supporting the efficacy of HBO therapy are not replicated. In addition, none of these trials used placebo group. Therefore, these results are not conclusive for the efficacy of HBO therapy for the treatment of autism. However, the promising effects of case series studies and the only multicenter, randomized, controlled trial encourage conducting further clinical trials with more rigorous scientific methodologies. In general, since control group should receive some pressure to stimulate HBO therapy, it is not practical to conduct a placebo controlled study for HBO therapy. Therefore, sham controlled studies are recommended to be conducted. Examining different pressures and oxygen levels is suggested, as well. Further studies should consider that more than half of patients with pervasive developmental disorders suffer from attention deficit hyperactivity disorder as a co-morbidity [35
Serious adverse effects are not reported in controlled studies. However, it does not guarantee that HBO therapy in higher pressures and oxygen levels is safe in autism. In fact, more studies including larger samples of patients are needed to be conducted.