Navigating "Medical" Approaches to Treating Autism

One doctor/autism parent recently mentioned to me that readers need to be made aware that drug interventions for autism can take time to show effect and that since parents see their child every day, they may not notice such gradual changes and potentially throw away a drug that actually is effective in their case.  This is indeed true.

On the other hand, as noted in their critique of Vitamin B6 use in autism, the Lurie Center for Autism at Massachusetts General for Children advised:

“It is difficult to track improvement or decline in children with autism because many have cycles of better, then worse, behavior, and many are also involved in more than one therapy that may change while the child is on supplements …

In our experience, although parents may see a change (positive or negative) in the short term, few continue to give megadose vitamin B6 to their children because of the difficulty in teasing out whether or not it really makes a difference and because of the activation and irritability seen in long term treatment.”

Some parents do not value small improvements, but if you combine five therapies, each with small improvements, the net effect can be substantial.

Some interventions have no side effects, unlike many B vitamins, and so it is just a question of whether there is a genuine benefit that is sustained.  If you stop the therapy, is the effect lost? albeit possibly gradually, and does the same benefit return when you restart the therapy?

As the child gets older, does the therapy continue to have value?  I recall being asked by Dr Ben Ari, how do I know after 8 years my son still benefits from Bumetanide? Every now and again we make a pause from Bumetanide and see how he responds.  How would you measure the response?  I use how good my son is at his online math tutoring program as an objective measure of cognitive status. I also ask him in the afternoon what he had for lunch that day; without bumetanide he usually cannot answer.

Another doctor who was treating his son with bumetanide and also low dose clonazepam for some years, told me that he ran out of clonazepam and decided to see if it still provided a benefit.  He concluded that clonazepam was no longer needed.  It is important to check; there is no point using a drug just for the sake of it.

Some people find a positive effect is lost and they need to readjust their dosage.  This seems quite common with sulforaphane.

As some readers have found, interactions between drugs and supplements mean that dosages may need to be adjusted. Low-dose clonazepam in particular has only a very narrow effective dosage range. Very many drugs, including verapamil, reduce the excretion rate of clonazepam and so increase the level in your blood. Vitamin E increases the metabolism of clonazepam.

An even more fundamental issue is whose interventions should you consider and where is line between potentially helpful therapies and crank therapies.

I am surprised how different clinicians react to other people’s therapies. For example, one US neurologist when introduced to the idea of potassium bromide as a therapy for autism and indeed pediatric epilepsy thought the idea was very interesting and lamented not being able to try it, while another US neurologist’s immediate reaction was “call child protective services”.  Both neurologists are well known autism doctors.

There are many widely shared approaches to treating autism, some are dietary like the gluten and casein free diet, the ketogenic diet or the popular GAPS diet; some use dietary supplements like fish oil and vitamins.  All approaches have their committed followers.

Most medical doctors are critical of any therapy claiming to treat autism; the few progressive mainstream doctors who do attempt to treat autism can be very disparaging about the methods used by others.  Of course, the most open-minded medical doctors are the ones successfully treating their own child's autism.

Some “protocols” that are put forward are presented as treating a very wide range of conditions (chronic pain, Alzheimer’s etc), far beyond just autism and this does naturally raise suspicions, but some conditions with very different symptoms can share similar underlying biology.

Mainstream medicine is by its very nature extremely conservative, cautious and slow moving.  Different countries may practice very different mainstream therapies and some techniques take 20 years to become adopted from one continent to another.  There is no single mainstream, it varies.

Progressive mainstream medicine gradually pushes the boundaries. In the world of autism such practitioners are mainly in the United States and surprisingly in Italy.

Science driven autism therapy stretches beyond progressive mainstream medicine. It takes many years for ideas in the scientific research to become part of medicine.  If you do not have a couple of decades to wait, you can choose to look at the science and identify what might eventually become medicine.

Applying an open mind to what might seem far-fetched alternative therapies can reveal alternative modes of action which are very much science based. Dr Yu has therapies for autism based on treating parasites.  It turns out that some anti-parasite drugs like Ivermectin and Suramin have modes of action that really should benefit some types of autism, but have nothing to do with parasites. 

If someone finds their Alpha Lipoic Acid (ALA) chelation therapy beneficial, this is not a surprise because ALA is an antioxidant widely used in medicine to treat diabetes and will benefit those with oxidative stress (autism, mitochondrial disease, cardiovascular disease etc).  It might have nothing to do with chelating metals from your brain. 

The DAN! (Defeat Autism Now) protocol was very popular and many people in the US still have a “DAN Doctor” who is applying the ideas of Sidney Baker, Jon Pangborn and others.  These are so-called biomedical therapies and mainly use dietary supplements rather than prescription drugs.  Defeat Autism Now!, closed down in 2011, was a project of the Autism Research Institute (ARI).

In North America there are doctors of functional medicine, integrative medicine, holistic medicine. There are naturopaths, homeopaths, doctors of Osteopathic Medicine (look for the DO after the name and not MD) and doctors of chiropractic medicine (DC after their name).

What is clear is that most autism parents prefer the idea of special diets, supplements and the simple protocols like that promoted by Nemechek, which are often claimed to work for everyone. 

I do not think many turn to Dr Chez and his book on medically managing autism; he does not claim to offer a simple answer and that is what parents want. 

I am amazed how popular Nemechek is and that people have even informally translated his book into different languages and then it gets shared virally.  It is like the new DAN! Protocol. I should note that his ideas do indeed work for some people.

You would think that having a doctor of medicine (MD) is best, but then nothing much about autism is taught at medical school.  Nemechek is a DO, not an MD.

I would have thought a clever neurologist like Dr Chez would be best, but I take note that many people have found an open-minded psychiatrist, who helps them trial off-label therapies, is best. This seems to be particularly true of adults with mild autism / Asperger’s.

There is no one-stop-shop for treating autism, no matter how big your budget is.  You have to navigate your own path, rather than just hoping for the best.  If you rule out off-label drugs, you are ruling out many potent therapies; it is rather like the "warrior" going into battle wearing a blindfold or having their hands tied behind their back.  The result likely could have been better.

FMT (Fecal Microbiota Transplantation) Super-donors and Abandoning the “One Stool Fits All” Approach

Not all stools were created equal

There was a comment recently left on this blog posing the question of what makes a good donor for FMT (Fecal Microbiota Transplantation), or a “poop transplant” in plain English.

FMT is actually an approved therapy for Clostridioides difficile infection (CDI). Research has shown  FMT to be more effective than the antibiotic vancomycin. To quote from the research, “The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin”.

FMT might not be for discussion at the dinner table, but it is highly effective in some instances.

FMT is actually far more widely used than you might imagine.  In one of today’s papers from China they had treated 1,387 people using 20 donors, for a wide variety of conditions.

In the US, autism researchers at Arizona State University showed a benefit that was maintained after a period of two years.

Autism symptoms reduced nearly 50 percent two years after fecal transplant

At two years post-treatment, most of the initial improvements in gut symptoms remained. In addition, parents reported a slow steady reduction of ASD symptoms during treatment and over the next two years. A professional evaluator found a 45% reduction in core ASD symptoms (language, social interaction and behavior) at two years post-treatment compared to before treatment began.

An earlier study with only vancomycin (an antibiotic) had found major temporary improvements in GI and autism symptoms, but the benefits were lost a few weeks after treatment stopped despite use of over-the-counter probiotics.

The obvious question to ask is whether FMT has a potential benefit to people with autism who do not have GI dysfunction.  I think this question is far from being answered.

We have seen in earlier posts that modifying the microbiome has great potential to fine-tune the function of the brain.  Researchers at UCLA showed that the high fat ketogenic diet controls epileptic seizures not through the action of ketones in the brain, but via the high fat intake changing the mix of bacteria in the gut.

The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet

FMT is just one way to modify the microbiome.  The UCLA researchers are developing a medical food to produce similar effects on the microbiome as the ketogenic diet.

Very likely a personalized bacteria transfer, customized to the symptoms of the person, might effectively treat many more conditions than just GI problems.  

It does look likely that for some conditions there may be super-donors, people whose microbiome is particularly effective, when transferred to others.

But the research cautions against what is called the “One Stool Fits All” Approach.  The donor and recipient need to be “compatible”.

The Super-Donor Phenomenon in Fecal Microbiota Transplantation

The microbial diversity of the donor is a good predictor of FMT success in the recipient. However, donor-recipient compatibility also plays an influential role in determining FMT success. Donor-recipient compatibility can stem from genetic factors such as differences in innate immune responses, or environmental factors including diet, xenobiotic exposure, and microbial interactions.

FMT for Inflammatory Bowel Disease (IBD): The Emergence of the FMT Super-Donor

IBD encompasses both Crohn's disease and ulcerative colitis; two debilitating disorders characterized by chronic relapsing inflammation of the intestinal. In contrast to CDI, there is no evidence that IBD results from an overgrowth of one specific pathogen. Rather, the disease is likely brought on by complex interactions involving the host's genetics, immune system, and gut microbiota. Both Crohn's disease and ulcerative colitis are broadly characterized by a reduced diversity of the gut microbiota with lower relative abundances of the Bacteroidetes and Firmicutes phyla and higher proportions of Proteobacteria. A specific reduction in the abundance of butyrate-producing bacterial species, particularly Faecalibacterium prausnitzii, has been observed for both Crohn's disease and ulcerative colitis. Meanwhile, for Crohn's disease, an increase in a pro-inflammatory form of Escherichia coli has also been reported.

The first successful case report of an FMT for the treatment of IBD was published in 1989 when a male with refractory ulcerative colitis achieved clinical remission for 6 months following a retention enema with healthy donor stool. Subsequently, a large number of FMT studies have been conducted on IBD patients with variable clinical outcomes, remission rates, and longevity of effect. Recently, Paramsothy et al. performed a systematic review and meta-analysis of 53 studies (four RCT, 30 cohort, 19 case studies) of FMT in IBD patients. Avoiding publication bias, their analysis of cohort studies revealed FMT was more effective at inducing remission in Crohn's disease patients when compared to patients with ulcerative colitis (52 vs. 33%, respectively). With regard to ulcerative colitis, a larger number of FMT infusions and a lower gastrointestinal tract administration were associated with improved rates of remission.

In contrast to studies of CDI, FMT studies conducted on IBD patients have frequently identified differential recipient responses that have been associated with variability in the donor stool. Currently, the stool used for FMT is not standardized in terms of donor selection (related vs. unrelated), preparation (fresh vs. frozen, aerobic vs. anaerobic), or the dose that is administered (single vs. multiple doses). While inconsistencies in FMT protocols make it difficult to compare different studies, there is a large degree of variability in clinical responses to FMT between recipients who have been subjected to the same study design. It is unfortunate that information on a recipient's genetic background or dietary intake is not yet routinely assessed, particularly given that some instances of IBD have an underlying genetic component. Due to the lack of genetic information, investigators have instead focused on the donor-dependent effect and proposed the existence of so called super-donors to explain the variation in recipient responses.

The first study to record the super-donor effect was a randomized control trial that was investigating the efficacy of FMT for inducing clinical remission in patients with ulcerative colitis. Moayyedi et al. assigned 75 patients with active disease to weekly enemas containing either fecal material or water (placebo) for a period of 6 weeks. FMT was shown to be superior to the placebo, resulting in significantly higher rates of endoscopic and clinical remission, albeit of modest effect (24 vs. 5%, respectively), after 7 weeks. Of the nine patients who entered remission, seven had received FMT from the same donor. Thus, it was argued that FMT success was donor-dependent.

Currently, it is not possible to predict the clinical efficacy of a donor before FMT in IBD patients. It has been suggested that remission rates could be improved by pooling donor's stool together, limiting the chances a patient will receive only ineffective stool. This stool pooling approach was recently investigated on an Australian cohort of 85 mild to moderate ulcerative colitis patients, in the largest randomized control trial of FMT for IBD to date. Rather than receiving FMT from just one donor, patients in the treatment arm were administered a stool mixture that contained contributions from up to seven different donors with the hope that donor-dependent effects could be homogenized. In addition to this, a far more intensive dosing program was adopted with an initial FMT delivered by colonoscopy that was followed by fecal enemas, five times a week for 8 weeks. Despite the multi-donor and intensive dosing approach, Paramsothy et al. achieved post-FMT remission rates (FMT, 27% vs. placebo, 8%, p = 0.02) that were similar to those reported previously. Notably, however, both clinical and endoscopic remission were required for primary outcome achievement in this study, whereas previous studies have mostly focused on either endoscopic or clinical remission rates alone. The pooled stool mixture was demonstrated to have higher microbial diversity than individual stool alone based on OTU count and phylogenetic diversity measures. Subsequent analysis of the different stool batches discovered that one donor appeared to exhibit a super-donor effect. Specifically, patients that received FMT batches that contained stool from this one donor exhibited a higher remission rate than those whose FMT batches did not include the super-donor (37 vs. 18%, respectively).

FMT for Other Disorders: Is There Also a Super-Donor Effect?

Evidence of FMT super-donors in other disorders outside of IBD is currently lacking. Case series and reports limit the capacity to identify super-donor effects because of limited sample sizes. However, despite the lack of large cohort studies, several studies have hinted at the possibility of a donor-dependent effect on FMT outcome. For example, in a short-term FMT pilot trial on 18 middle-aged men with metabolic syndrome, FMTs from lean donors (allogenic FMT) were found to correspond with a 75% increase in insulin sensitivity and a greater diversity of intestinal bacteria in the recipient compared to autologous FMTs (recipient-derived). It was later noted that the patients who experienced a more robust improvement of insulin sensitivity post-FMT had all been in receipt of the same donor. In a subsequent study on 38 Caucasian men with metabolic syndrome, lean donor FMT also resulted in a significant improvement in peripheral insulin sensitivity at 6 weeks. However, this effect was lost by the 18 week follow up. For the allogenic FMT, 11 lean donors were used, seven of which were used for more than one recipient. Whilst donor-dependent effects were not reported, the authors noted that the “multiple fecal donors might explain the transient and variable effects seen in the allogenic group.” As FMT research in this field progresses from small-scale case series to larger-scale randomized placebo controlled clinical trials, it remains to be seen whether the super-donor phenomenon generalizes to other conditions outside of IBD.

Abandoning the “One Stool Fits All” Approach

Microbial dysbiosis is a blanket term for an unhealthy or imbalanced gut community. As such, the population structure that is considered to represent microbial dysbiosis is variable between different disorders. Moreover, the microbiome deficit of one individual may not necessarily mirror that of another individual and therefore it is not surprising that patients respond differently to FMT. As more FMT-related clinical and microbial data are generated, it is becoming clear that “one stool does not fit all” in the context of treating chronic diseases with microbial dysbiosis. Equally so, the selection of donors based solely on clinical screening guidelines provides no guarantee of FMT success. It appears a patient's response to FMT predominantly depends on the capability of the donor's microbiota to restore the specific metabolic disturbances associated with their particular disease phenotype. If this is true, a donor-recipient matching approach, where a patient is screened to identify the functional perturbations specific to their microbiome, may be the best way forward. The patient could then be matched to a specific FMT donor known to be enriched in taxa associated with the metabolic pathway that needs to be restored. Immune tolerance screening would also be beneficial for reducing the impact of donor-recipient incompatibilities stemming from underlying differences in innate immune responses.

Framework for rational donor selection in fecal microbiota transplant clinical trials

Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.

Association Between the Clinical Efficacy of Fecal Microbiota Transplantation in Recipients and the Choice of Donor

Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. 

Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively.

During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups.Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. 

Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05).

In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant. 
In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P

Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.

Conclusion

FMT in practice today does look rather primitive, but seems to be beneficial more than half of the time, even in autism in the Chinese study.

As expected, different donors have different efficacy in different diseases.  As FMT becomes more popular you would expect that more super-donors will be stumbled upon and then clinicians will have a better chance to match the donor to the recipient.

For certain GI conditions that do not respond well to current drug therapy, FMT does look a good option to investigate.  The level of success is likely to vary depending on the availability and selection of the donor.

It does seem that orally ingested bacteria in the form of probiotics often do not colonize the gut as hoped for, and just past straight through, with only a limited and transient effect.  The fact that FMT can have a very long-lasting effect is remarkable and likely due to the fact that these bacteria are direct from another human.

Modifying the microbiome is only now emerging as a treatment idea and it will take many decades to fully develop it.

Ingesting a mix of another human’s bacteria is not without risk.  

Massachusetts General Hospital oversaw trial that led to the first death from a fecal transplant, a new paper shows

This spring, a 73-year-old man with a rare blood condition became the first person to die from drug-resistant bacteria found in a fecal transplant. New details about that unprecedented incident emerged on Wednesday.

The man was a participant in a clinical trial run at Massachusetts General Hospital and received fecal transplant capsules made in November with fecal material from one stool donor, according to a paper published Wednesday in the New England Journal of Medicine. Tests after the man’s death revealed that material contained a rare type of E. coli bacteria.

FMT seems to be becoming fashionable, with all kinds of people offering it.  The American Journal of Gastroenterology even published a study on Do-it-Yourself FMT. "Almost all indicated that they would perform DIY FMT again, though many would have preferred to have FMT in a clinical setting."  I would vote for the clinical setting and a carefully selected/screened donor. 

Why is the evidence for Early Intensive Behavioral Intervention for Autism so weak?

One to one autism therapy is pricey – is it worth it?

Only a handful of countries widely apply behavioral interventions to treat toddlers diagnosed with autism.  Behavioral interventions include Applied Behavioral Analysis (ABA), Verbal Behavior (VB), Pivotal Response Treatment (PRT) and the Denver model.

Even after several decades, the published evidence that these interventions actually work is quite weak.  This explains why most countries do not readily provide public funds for ABA.

In the US, efforts are being made to diagnose autism at younger and younger ages, because the child can then benefit from these “proven” interventions, that other countries do not believe work.  Who is right?  

You can read Manuel Casanova’s perspective at the end of this post.  He is not such a fan of expensive US developed therapies and concludes:-

"spending time with your children and group socialization, in my experience, have provided the most favorable outcomes"

Does ABA work?  If so, why can’t you prove it?

From my personal experience, behavioral intervention was very beneficial as a teaching method, but it does not make autism go away.

In today’s study the aim was to determine if behavioral intervention is cost effective.  The conclusion based on all the studies considered is that there is no conclusive evidence that behavioral intervention is cost effective.  So logically the countries that do not widely fund it, like the UK, can be reassured that they are on the “right side” of the argument.

My view is that is that autism is so heterogeneous you can prove almost nothing, with any degree of certainly.  It is always going to be a case of ifs, buts and maybes.  This also very much applies to clinical trials of drugs to treat autism.

Why did ABA ever catch on in the first place?  People want hope and the more expensive something is, the more people want it.  Forty hours a week of ABA is very expensive and nice to have, if someone else is paying.  

We saw in an earlier post that Lovaas (the founding father of ABA) later admitted to selectively retiring non-responders from his clinical trials, to improve the apparent success of his methods.  This pretty much means you have to ignore all his data and his papers should be retracted. 

Many parents want curative treatments for autism.

Lovaas claimed that ABA is curative and that the treated kids end up like typical kids.  Sadly, this is an exaggeration.

Is two years of ABA cost effective for severe autism?  I guess it depends whose money is paying for it.  Is two years of ABA going to be life changing for a person with severe autism?  Unfortunately, even after 20 years of ABA, that person will likely still have severe autism, if you have not treated their underlying biological problems.

Some parents rave about ABA and make comments like “after two years of ABA my son now makes eye contact”.  Great, but would you pay $120,000 of your own money for that?  I think not.  Should your local government regard that as money well spent?  I think they should be more demanding; the results of just $1,000 spent on the right personalized medicine will be much more impressive.

Today most people currently being diagnosed with autism have mild cases.  If they can talk and do not have intellectual disability (ID) / mental retardation (MR), they will likely see little benefit from 40 hours a week of discrete trial training.  It would be a huge waste of money and probably just annoy the child.  

Many children with mild autism need a different kind of therapy, they need to learn social and emotional skills they may not naturally possess - how to make friends, how to avoid making enemies and so how not to get bullied at school.  This will only be effective started very young, before being a victim becomes a badge of honour.

Interventions based on early intensive applied behaviour analysis for autistic children: a systematic review and cost-effectiveness analysis

Autism is a lifelong condition that affects how people understand the world and interact with others. Early intensive applied behaviour analysis-based interventions are an approach designed to help young (preschool) autistic children. This approach is often delivered on a one-to-one basis, for 20–50 hours per week, over a period of several years.

This project obtained and analysed the original data from studies of early intensive applied behaviour analysis-based interventions, to determine whether or not these interventions are beneficial. It also investigated whether or not the interventions represent good value for money.

The results suggest that early intensive applied behaviour analysis-based interventions may improve children’s intelligence, communication, social and life skills more than standard approaches. However, some results could be inaccurate or incorrect, and there was no evidence about other important outcomes, such as the severity of autism and where children went to school. Most studies lasted for around 2 years, which means that it is not known if early intensive applied behaviour analysis-based interventions have meaningful long-term benefits.

It was not possible to fully assess whether or not these interventions provided value for money, as the benefits of early intensive applied behaviour analysis-based interventions were unclear, although the available evidence suggested that they did not. Early intensive applied behaviour analysis-based interventions may, however, provide value for money if their effects were to last into adulthood, or if receiving early intensive applied behaviour analysis had a large impact on the type of school children attended.

Future studies of early interventions may be helpful, but should consider looking at which components of early applied behaviour analysis-based interventions are the most important, rather than at whether or not they work better than other interventions. Future studies should also follow best current research practice and evaluate outcomes that matter to autistic people and their families. 

Economic evaluation

Using National Institute for Health and Care Excellence decision rules to benchmark the results of the cost-effectiveness analysis and adopting a £30,000 (USD 40,000) per quality-adjusted life-year threshold, these results indicate that early intensive applied behaviour analysis-based interventions would need to generate either further benefits or cost savings to be considered cost-effective.

Implications for service provision

Although individual participant data meta-analyses have shown small to moderate improvements in child cognitive ability and adaptive behaviour for early intensive applied behaviour analysis-based interventions relative to treatment as usual or eclectic approaches, all of the identified studies were at risk of bias, limiting the strength of conclusions that can be drawn from these results. Furthermore, results from individual studies varied considerably, with some showing no relative benefit of early intensive applied behaviour analysis-based interventions. 

Conclusion

For cases of severe autism, if you can afford intensive (and expensive) 1:1 intervention of any credible kind (Floortime, ABA, Denver etc - whatever works best in your case) it makes sense to use it.  It should improve skill acquisition and will make the parents feel better.

None of these interventions are curative, the child will still have autism.  When you no longer pay for the 1:1 intervention, the effects most definitely will start to fade away.  Don’t mortgage your house to pay for ABA.

Nothing stops you making your own 1:1 intervention program using family, friends and volunteers.  This does not cost much and is sustainable over many years; it is likely to be much for effective that 2 years of "professional" therapy.

I do find it odd that in the US there is free early intervention for toddlers and then provision just stops, as if it suddenly is no longer needed.

If you use ABA to teach a child to tie shoe laces, he/she will retain the skill as long as you keep buying shoes with laces.  If you do not practice/apply the skill for 6 months, do not be surprised if it has to be re-taught.

Our final ABA consultant was very experienced, she worked for 10+ years in the US before moving home to Athens, Greece.  She told me that in her experience all children with autism benefit from ABA, but the level of progress they make varies widely.  If a child does not respond to ABA, it very likely is not being done correctly.  ABA should be seen as fun, not like a punishment. If your child hates ABA sessions, they have no chance of working.

I come back to my earlier recommended strategy. Find your most effective novel medical treatment, which will inevitably be a polytherapy and combine this with a method of learning that works best for your particular child.

Then just keep going and let time do its work.

In countries like the UK, with free health and education provision, the government does not generally pay for early intervention because their medical advisors do believe it to be cost effective, which really means they think it does not work and so do not want to pay for it.  The cynic might just say they do not want to fund it. 

The idea was supposed to be that by investing upfront in ABA during the early years, you save money later on, by having a more functional child and then adult who requires less expensive provision.  Unfortunately, there is absolutely no proof this is true.  

If you go from early intervention, to an ABA special school and then ABA college, things clearly did not work out.

In the US early intervention is assumed to be very effective and the current idea is that doctors should hurry to diagnose autism before 24 months so as to get into the intervention program as soon as possible.  Where is the evidence to support the US view?  Are US outcomes any better?

We saw in recent research from UC Davis that looked at outcomes over time in autism that the best outcomes are not associated with any particular therapy.  The best outcomes happen because of the biological characteristics of that child, rather than any amount of behavioral intervention.

I expected the UC Davis study to show a relative benefit for those who received ABA therapy, but it did not.  We do have to take note.  I am actually pro-ABA and have spent a vast amount of money on this kind of therapy and 1:1 instruction.   

Ignoring treating the biological dysfunctions in autism while spending hundreds of thousands of dollars on 1:1 therapy and special education does not make a lot of sense.

Here is a relevant excerpt from a recent post by the neurologist, autism researcher and autism Grandfather, Manuel Casanova, from his Cortical Chauvinism blog: -

AUTISM: HOW CULTURE INFLUENCES OUTCOMES

Despite marked differences in geography, non-Westernized countries see autism as a social responsibility rather than a medical condition.  These countries offer a collectivist perspective that downplays individuality and prioritizes maintaining relationships within a given group of people.  In this regard, I have often marveled as to how vastly different countries, like Colombia and the more desolate regions of Eastern Russia (Siberia), share similar perspectives regarding autism. Indeed, due to a lack of resources, interventions in these countries are usually parent-mediated and heavily influenced by cultural norms.  Lack of personnel trained in behavioral analysis has been supplanted by art and music instruction.  Classes are provided in group settings where outperforming other members is not seen as conductive to the overall benefit of the group. Members are encouraged to adopt the norms of the group while teachers emphasize cooperation and nurturing. Students arrive early to school to participate in team building exercises.

I have often marveled at the achievements of troupes of autistic children performing autochthonous musicals and their accompanying choreography.  Adopting the norms of the group have served them far better than any Westernized behavioral intervention.  Participants in these groups seem genuinely happy; in part, given the sense of achievement at contributing to a piece of artistic expression.  In addition, the structured activities in such groups offer norms that minimize uncertainty.  Participants feel a sense of security in a group that fast becomes their extended family.

Autism is a medical condition but, without a cause that we can target, treatment options have remained symptomatic.  This is one of the reasons for looking at other countries and learning what has worked for them.  Indeed,  I believe that we can gain from adopting the cultural perspective of other countries to benefit our own children. Whether it is an improvisation on an autism chair, electroacupuncture, or using a zen bowl, spending time with your children and group socialization, in my experience, have provided the most favorable outcomes.

Manuel is one of a very small group of thoughtful researcher-clinicians, who have been working in the field of autism for decades, like Dr Kelley from Johns Hopkins and that psychologist Dr Siegel who wrote the Politics of Autism and revealed how Lovaas really did his "research". 

Manuel's researcher son-in-law is interested in precision medicine and drug re-purposing, I guess driven by his own young son's rare genetic "autism", NGLY1 deficiency. This very severe condition leads to the body not being able to breakdown and remove damaged and misfolded proteins.  You would think that reducing Endoplasmic Reticulum (ER) stress, that produces misfolded proteins, might be useful. This was covered here, along with a long list of possible therapeutics:-

https://epiphanyasd.blogspot.com/2019/12/er-stress-and-protein-misfolding-in.html

Some readers are following the details of the Covid-19 situation.

The Indian Experiment rather than the Swedish Experiment

A recent study suggests that more than half of the 6 million slum dwellers in Mumbai have had Covid-19; another 6 million do not live in slums. Government research showed that in the capital Delhi 23% have Covid-19 antibodies.

Mumbai slums have an extremely high population density, extreme poverty and so not much social distancing. So they show what Covid-19 does with no serious intervention, better than Sweden does.  Mumbai has reported 6,200 deaths in total.

You can extrapolate from the data (57% of slum dwellers and 16% of non slum dwellers with Covid antibodies) for the total 12 million population of Mumbai.  4.4 million had the virus and 0.14% died.  In the worst case scenario, when everyone finally gets infected in the next few years, there would be another 7.4 million with the virus and another 10,800 deaths.  The death/mortality rate for the city would be 0.14%.  (In reality it will probably be less than 0.14%, because some people will not get the virus)

The 0.14% Covid-19 mortality rate compares to the 2.5% mortality rate of the 1918/9 global flu pandemic; worse still that flu pandemic affected fit young people the most, making the demographic impact huge. 

The crude death rate from all causes in the US is around 0.8% each year (just 0.7% in India).  That puts the 0.14% from Covid-19 into some perspective. If Americans are as healthy as Indians and India did not under-report the number of Covid deaths in Mumbai (both are big ifs), you could apply the 0.14% mortality from Covid-19  to 330 million Americans and get 460,000 people. I think the realistic number would be higher, given deaths to date in the US.  

I think the world has been very lucky to have been affected by a pandemic that has such a low mortality rate.  It could easily have been 20 times worse, perhaps next time?  In the Middle Ages, the Black Death killed hundreds of millions of people - a truly apocalyptic pandemic.

There is no certainty that a vaccine is going solve the Covid-19 problem, indeed the UK government is buying 12 different vaccines, in the hope that one is effective.  Vaccines are often least effective in older people, who are main risk group for Covid-19.

If no vaccine turns out to be 90% effective, the Mumbai slum dwellers and the Swedes will have been the smart ones.


Controlled Infection vs Vaccination

If I was a dentist I would be seriously worried about Covid-19. I would favor a small infection today, caught from my party-going offspring, rather than in two year's time catch it while peering into a stranger's mouth during an hour long procedure, and get a huge initial exposure, leading to a more severe infection.  The fact that Mumbai policemen, London bus drivers and of course doctors and nurses without good PPE have had so many fatalities does suggest the amount of virus you are initially exposed to is a critical factor to the outcome.  This would be logical anyway.

I am really glad at least my older son and myself have had Covid-19.  If I was a dentist, I would be hugely relieved. A few months ago we assumed Covid-19 was both highly infectious and often deadly, now we know the reality.  If you are youngish, slim and healthy the risk is very low.  Many in rich societies are old, overweight and in poor health.

I did take my younger son Monty, aged 17 with autism, for a visit to the dentist two months ago and I really felt sorry for her.  She was wearing a mask, but that is no guarantee of her safety.