This week Biomed central published a double-blind placebo study of the effectiveness of hyperbaric treatment for autism. The study was published in Biomed, which is an open access journal, so readers are invited to read the entire study here. In sum, the authors randomly assigned 62 children (52 boys, 10 girls) between the ages of 2 to 7 to either a hyperbaric treatment condition or a control condition. The treatment involved 40 1-hour sessions for 4 weeks (2 sessions per day 5 times per week). After the study, all participants in the control group were offered the opportunity to receive 40 hyperbaric treatment sessions.

The authors found that hyperbaric treatment resulted in significant improvements in overall functioning, receptive language, social interaction, and eye contact. These findings were affected by the age of the child, in that children over the age of 5 showed more improvement to the treatment than children under 5. In addition, the treatment did not seem to work for children with an initial ADOS score above 50th percentile. The authors then argue that the treatment is most effective with children with more severe autism (ADOS score below the 50th percentile).

In general, the study design was strong. The authors made great efforts to make sure that the two treatment conditions were nearly identical. That is, kids in the control condition were exposed to procedures that mimic the real hyperbaric treatment (being inside the chamber, etc). Thus, it is very unlikely that the results observed were due to a placebo effect. The study also moves in the right direction by presenting evidence for the efficacy of treatments that are usually considered controversial or untested. We need more research on alternative treatment interventions that will help us determine which interventions are actually effective.

UPDATE: Please make sure you read the comments below for additional discussion on other limitations of this study.

Despite the merits of the study, I know that many people will have concerns about the authors’ conflict of interest. I quote directly from the article’s conflict of interest statement (initials refer to each author):

DAR, LWR, SS, CS, AU, JN, EMM, and EAM treat individuals with hyperbaric treatment in their clinical practices and derive revenue from hyperbaric treatment. DAR, LWR, and EAM had previously received research funding from the International Hyperbarics Association for an earlier study of hyperbaric treatment in autism [7]. EAM has also received hyperbaric chambers and financial support (unrelated to this study) from OxyHealth LLC for remodeling the Rimland Center, a center for mentoring clinicians interested in learning how to care for children with autism spectrum disorders. The remaining authors (SL, GH, and BG) declare that they have no competing interests.

Often research is published by authors who have conflict of interest (receiving consulting payments from a drug company for example), but it is unusual for the majority of authors of a study to have direct conflict of interests. The authors are probably aware of this, so I am surprised that the authors did not include as collaborators any academic researchers with permanent research appointments at a research university. Having a reputable university team serve as umbrella for this study would have greatly appease readers who will have concerns about the conflict of interest involved.

UPDATE: Please read the comments for additional discussion on several issues related to the limitations of this study. I’m most concerned about the authors’ apparent misrepresentation of previous studies on HBOT treatment in cerebral palsy (I’m not sure how this made it through the reviewers at BMC).

Rossignol, D., Rossignol, L., Smith, S., Schneider, C., Logerquist, S., Usman, A., Neubrander, J., Madren, E., Hintz, G., Grushkin, B., & Mumper, E. (2009). Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial BMC Pediatrics, 9 (1) DOI: 10.1186/1471-2431-9-21

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14 Responses to Hyperbaric treatment for children with autism: First controlled clinical trials.

  1. Anonymous says:

    I don't know about its effects on autism, but I have done a meta-study on the effects of hyper-baric treatment on cerebral palsy. It seems like there are no positive effects, there can even be dangerous side-effects.

    Here's a list of studies you might want to check out:

    Collet et al. (2001). Hyperbaric oxygen for children with cerebral palsy: a randomised multicentre trial. Lancet. 23;357(9273):2052-3.

    McDonaugh et al. (2007). Systematic review of hyperbaric oxygen therapy for cerebral palsy: the state of the evidence. Developmental medicine and child neurology. 49(12):942-7.

    Muller-Bola et al. (2006). Side effects of hyperbaric oxygen therapy in children with cerebral palsy. UHM. 33(4).

    Patel, Dilip R. (2007). Therapeutic intervention in cerebral palsy. Indian journal of pediatric, 72(11).

    Papasian & Alfonso (2003). Tratamiento de los niños con parálisis cerebral con oxÍgeno hiperbárico. Revisia de Neurologia. 16-31;37(4):359-64

    Rocksworld et al. (2007). Hyperbaric oxygen in traumatic brain injury. Neurol Res. 29(2):162-72.

    Sukoff, J Neurosurg. Effects of hyperbaric oxygenation. Journal of neurosurgery. 94(3):403-11.

  2. Thanks for the post. As you can see, this was the first controlled study about the use of hyperbaric treatment in autism. The conflict of interest of the authors will raise many questions and parents may be skeptical, so I think it is critical to have many more studies on these type of treatments. As you know, one major issue with research on alternative treatments is that it not usually conducted by traditional academic researchers with no conflict of interests, which has an impact on the publication bias effect.

  3. Anonymous says:

    This paper provides on confidence intervals … would like to see. Curious that they were not provided. Would seem to be a standard reporting criterion.

  4. Anonymous says:

    “In general, the study design was strong. The authors made great efforts to make sure that the two treatment conditions were nearly identical. That is, kids in the control condition were exposed to procedures that mimic the real hyperbaric treatment (being inside the chamber, etc). Thus, it is very unlikely that the results observed were due to a placebo effect.”

    I disagree. The study reported outcomes in largely subjective measures, including parental reports. The parents were present in the pseudo-hyperbaric chambers with their children. The procedures didn’t mimic real hyperbaric treatment. The procedures attempted to replicate the same procedures for inflating a 4 PSI portable (inflatable) hyperbaric chamber between groups. If you think it’s likely that parents could not tell the difference between one of these chambers being slightly inflated, and then deflated to “barely inflated” for the remainder of the treatment and being inflated to 4 PSI and staying there, you might do well to be a little more skeptical.

    Placebo effect by proxy of the parents could easily explain the observed results.

    Re: the potential COI and bias

    “The authors are probably aware of this, so I am surprised that the authors did not include as collaborators any academic researchers with permanent research appointments at a research university.”

    Why would any academic researchers at a university sign up to collaborate to study a “treatment” that provides no more increased oxygen tension than simple O2 therapy alone (at 1/10 the price)? Perhaps it might seem unethical to some.

  5. Thank you for your post.

    My statement about the “study design” being strong, is based on comparing this study with other similar clinical studies. The fact that they collected subjective parent reports of improvement is not unique to their study and extremely common in psychopathology research. Yes, there is controversy as to the validity of parental measures, but this is not a settled issue as many have argued (and shown compelling empirical data) for the validity of subjective parental reports as outcomes in clinical research (see for example Biederman et al. 2004 in Pediatrics, Volume 113).

    The issue you raise regarding the possible placebo effect is compelling. Clearly you are more familiar with this treatment and in your opinion parents were probably aware of who was receiving the treatment and who was receiving the placebo. The authors argued that the procedures were tested with adults who could not differentiate between the treatment and the placebo. But it is possible that these adults were not familiar with the procedures (or as informed as the families) so the possibility of a placebo effect still stands.

    I don’t want to sound like a cheerleader for this study or the authors. There is a major conflict of interest that is indisputable.

    Thank you again for your post. Nestor.

  6. If you note from the original paper, they cite the Collet study Anonymous references above as supporting the hypothesis that hyperbaric treatment works in CP. I can’t access because it’s behind a paywall, so I can’t confirm or deny that either way, although Anonymous cites it as not supporting (and I’d thought the jury was back years ago saying that hyperbaric treatment for CP was useless or worse than useless).

    The other thing that really jumps out at me is that the authors of this study don’t seem to have a clue what their proposed mechanism of action is. They say, “The mechanism of action of hyperbaric treatment in
    autism is not entirely known, although it may act by diminishing gastrointestinal and cerebral
    inflammation and by improving immune dysregulation and cerebral hypoperfusion.” In other words, they’re making what lay-people call a “wild guess.” That rings a lot of alarm bells to me.

  7. You are correct. The Collet study found no differences between the treatment and control group. from the study:

    “This study shows that hyperbaric oxygen treatment in children with cerebral palsy does not produce any improvements greater than those seen in children treated with slightly pressurised air.”

    You are also correct about the “Wild Guess”, although, sadly, there are many standard treatments for many psychiatric and medical conditions that are effective yet the mechanisms of actions are unknown.

    Thanks for posting.

  8. Nestor thank you for this balanced “translation” of the recent HBOT-Autism study.

  9. M says:

    Hi Nestor. First of all, I am impressed with this site! How do you have the energy for all of this? :)

    And now, I couldn’t depart from this site before making a comment about the use of the ADOS. I have not read this article, but your post suggests that the authors of this study used the ADOS as a measure of severity. This is a serious flaw bc the ADOS is a classification tool and as it is currently scored, is not at all designed to be a measure of severity.

  10. Thanks M. Although the authors did not use the Ados as an “outcome” measure, they did use the ADOS as a proxy for severity. I quote: “Autism severity. Post-hoc analysis of children in the treatment group demonstrated that those
    who had an initial ADOS score below the 50th percentile for all children (less initial autism
    severity) had similar improvements in ABC total score and subscales compared to children with
    an initial ADOS score above the 50th percentile (p = ns).”

    This reminds me of the issue we have in our field with people using the CDI as a diagnostic instrument :-)

    Thanks for visiting!

  11. Dr Chun Wong says:

    It’s such a shame that this clinical study is being criticized. It’s great news for the autism world and backs up what many parents and therapists already know. Side effects are very rare with HBOT, especially when you compare it to standard drug therapies.
    Yes, I’m biased but only because I know HBOT works, otherwise I wouldn’t use it.

  12. A Family says:

    My son with autism is doing HBOT (hyperbaric oxygen therapy–hard chamber) and we have seen very good results. It is costly, but well worth it! We do intense ABA and would not take that away either. My son is only 2, and even with his age, HBOT has really changed him for the better. THank you for this great post!

  13. Liz Ditz says:

    Hi Nestor.

    I don’t know if you read LeftBrain/RightBrain or A Photon in the Darkness.

    Prometheus, a long-time anonymous blogger, published a critique of this study at both sites:

    http://leftbrainrightbrain.co.uk/?p=2055

    Which begins

    “A few weeks ago, BMC Pediatrics published an article that purports to show that Hyperbaric Oxygen Therapy (HBOT) can produce “…significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness..” in autistic children. This study (Rossignol et al, 2009) is billed as a “…multicenter, randomized, double-blind, controlled trial.”

    It’s all that and much, much less.”

    Dad of Cameron (Do’C) another long-time anonymous blogger (Autism Street) had additional criticisms, guest-blogged at LeftBrain/RightBrain

    http://leftbrainrightbrain.co.uk/?p=1987

    I see what looks like a pretty significant error in the methodology of this study. It’s one of those types of potential errors that stand out like a strobe light or a siren – it’s really tough for me to pretend it’s not there.

    [snip]
    Both the paper and ClinicalTrials.gov2 list the Center for Autism Research and Education, Phoenix, Arizona, as a study location. This is a problem, because the stated treatment pressure in the study (1.3ATM) seems highly unlikely to actually be achievable in Phoenix with the equipment that was apparently used for this study.

    As described in the section titled, “Interventions”:

    “These procedures included covering control switches, inflating and deflating the chambers to simulate pressure changes, and masking the sounds from the chambers.”

    The use of inflatable monoplace hyperbaric chambers, is a clear indication that the actual total pressures (and quite likely results of this study) would have been affected by the ambient air pressures at the times and locations of treatment. In fact, the ambient air pressure is the largest component of the stated treatment pressure in this study (ambient pressure + added treatment pressure = total treatment pressure).

    So. Problems with the assessment instruments. Problems with blinding. Problems with the actual degree of HBOT being administered.

  14. Thanks Liz for the information and the links. I was not aware about the possible confound regarding the altitude of Phoenix. Unfortunately I’m not familiar enough with the relevant issues involved (ambient pressure issues) to be able to elaborate. Clearly this study has some methodological issues that go beyond simply high level of financial conflict of interest on the part of most of the authors. Thanks, Nestor.

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