THE MEDICAL MAZE
Picture this scenario. You walk out of the paediatrician’s
rooms in a daze, after hearing that your child has an Autism Spectrum
Disorder. You go home, log onto the Internet and look up the ‘official’
websites, which all say something like this: ‘Autism is a life-long
disability. There is currently no known cure’. But then you start
searching further and discover seemingly dozens of websites offering
treatments which they claim can ‘cure’ or ‘reverse’ autism. What’s
going on? Are these claims to be believed? Who’s right?
Unfortunately the official view is much closer
to the truth. There is no ‘miracle cure’ for Autism. The very fact
that there are so many and varied therapies is testimony to that.
As Joe’s paediatrician succinctly put it, ‘if there was a cure for
autism, there would only be one cure.’ This quote probably sums
up the current situation best:
When you have many medical therapies, often contradictory,
two possibilities exist. One is that the correct therapy for that
disease has yet to be identified. The history of medicine is replete
with incidents in which multiple, unsatisfactory therapies are offered
until the single effective treatment for a single disease is discovered.
The second possibility is that there is no such thing as one medical
treatment because Autism is not one disease after all, but a syndrome,
a final common pathway of many, many different diseases, each of
which may require its own medical therapy. In such cases accurate
diagnosis must precede therapy.1
But let’s not be too pessimistic. Researchers
throughout the world are strenuously working to improve our understanding
of Autism and to search for more effective treatments for this perplexing
condition. The future of a child diagnosed today is much more promising
than that of a child diagnosed only 10–15 years ago. And while there
may be no quick fix there is certainly a lot you can do to help
your child right now.
Remember that Autism Spectrum Disorder is a spectrum — a spectrum
which ranges from people with a significant disability (low functioning
Autism) to very high functioning people who can cope pretty well
in the world with little or no support. There are many examples
of able people with Autism Spectrum Disorder going on to lead successful
adult lives and, whilst Autism may remain a life-long condition,
for these people at least, it is not much of a ‘disability’.
Current interventions aim to reduce your child’s
symptoms and equip them with new abilities, at very least to reduce
the level of their disability and at best to give them the opportunity
to live a near normal life. This is not something that can be achieved
overnight. It will probably be a long and difficult journey which
may require a multi-pronged approach of early intervention, speech
and/or occupational therapy, medication and, for some people dietary
changes and complementary medicines.
With this sort of approach a very few lucky children
will improve so much that their symptoms will all but disappear.
These children are sometimes referred to as ‘recovered.’ Maybe your
child will be one of the fortunate few, but the majority will not.
Whatever the case, please don’t lose sight of how much they do improve
and learn, become ‘more able than disabled’, as you pursue the ‘Holy
Grail’ of recovery.
The main way we can help our children is through
early intervention. In this chapter we will talk about how medicines
can be used to control some of the more disabling symptoms of Autism
Spectrum Disorder and related conditions, and then delve into the
more controversial area of complementary and alternative medicines,
the so-called biomedical approach. But first, evidence-based treatments,
what are they and how you can use them to maximise the effectiveness
of your child’s intervention program?
What are evidence-based treatments?
Imagine another scenario. You speak to a well-respected
paediatrician, an expert in their field. When you ask about a complementary
therapy for Autism Spectrum Disorder they say, ‘There is no evidence
to support its use.’ You visit a biomedical practitioner anyway
and they say there is ‘lots of research’ to support this therapy.
Who’s right this time? Well, it might interest you to know that,
technically, they both could be. It’s how you interpret the word
evidence.
There is mind-boggling amount of research out
there about Autism Spectrum Disorder but not all of it is of equal
value when it comes to evidence of treatment effectiveness. It’s
all about trying to establish cause and effect. The hierarchy of
evidence runs from the weakest (the anecdote) to the strongest (the
randomised, double-blind, placebo-controlled clinical trial).
The problem with Autism Spectrum Disorders is
that the most emotionally powerful stories for parents often are
the anecdotal. Anecdotes are great because they can personalise
the stories of the various interventions. But they are not considered
good evidence.
For example, say you read a story of a mother
whose child starts talking after going on a gluten-free casein-free
diet. You’d be tempted to rush off to the health food store there
and then in the hope that the same thing happens with your own child.
But just because B (child starts talking) follows A (starting of
GFCF diet) doesn’t definitely mean that A caused B. It might suggest
that possibility, but it doesn’t prove it, because we haven’t controlled
for all the variables. It could be that the child was just ready
to talk (many children with Autism Spectrum Disorder do learn to
speak without intervention), or it could be a result of the child’s
other educational interventions and/or speech therapy finally bearing
fruit. We really can’t be sure.
So when a specialist says there is ‘no evidence’
what they are really saying is that there is no evidence of the
quality that can really establish cause and effect. So let’s look
at the different components of a randomised, double-blind, placebo-controlled,
clinical trial to see why these trials are the most powerful research
tools we have.
A clinical trial is a research study conducted
with patients which tests out a medicine or other intervention to
assess its effectiveness and safety.2
This is an important distinction. A lot of the research published
about Autism Spectrum Disorder is actually not in the form of clinical
trials but descriptive (or observational) research. Examples might
include a parent survey looking at the frequency of gastrointestinal
symptoms in children with Autism Spectrum Disorder, or a study which
measures the blood levels of the neurotransmitter serotonin in Autism
Spectrum Disorder children at a single point in time. This sort
of research is absolutely vital but does not provide any evidence
of cause and effect; it is a means of generating theories to be
tested in future clinical and other research.
Unfortunately this sort of research is often reported
uncritically by the media and afforded much more significance than
it might actually merit (think about all the ‘major cancer breakthroughs’
you’ve heard about but yet we still haven’t eliminated cancer).
Each of these individual studies is a tiny piece in an enormous
puzzle, a very small step towards improving our understanding of
Autism Spectrum Disorder, but by no means the ‘answer’.
A controlled clinical trial is a study testing
a specific medicine or other treatment involving two (or more) groups
of patients with the same disease or condition. One (the experimental
group) receives the active treatment (that which is being tested)
and the other (the control group) receives an alternative treatment,
a placebo, or no treatment.
Control groups are needed to determine whether
the intervention actually caused the observed change and to rule
out other possible explanations. For example, if a group receiving
intervention X improves you might conclude that intervention X is
effective. But if the control group (who did not receive intervention
X) also improves to the same degree, something other than X was
responsible. This was the problem highlighted with the TEACCH research,
discussed earlier. There was no control group so we cannot say definitely
that the IQ gains reported were as a result of the TEACCH program
or just a consequence of natural progression.
Randomisation is a method similar to tossing a coin to assign patients
to treatment groups; the ‘active treatment’ is given if the coin
lands heads and the control is given if the coin lands tails (in
reality this is usually done by a computer program). In randomised
controlled trials each person has an equal chance of receiving the
active treatment, which avoids any possibility of selection bias
in a trial. Selection bias is where the people delivering the treatment
might be (subconsciously) tempted to give the real treatment to
the people they think most likely to benefit (or perhaps in the
case of children with Autism Spectrum Disorder, those whose parents
look the most likely to carefully follow the treatment regimen).
Also, if the number of participants in the study is large enough,
randomisation should ensure that the active and control groups are
well matched for any other factors which could affect the outcome,
such as age, IQ etc.
A placebo is a dummy or inactive treatment which is given to the
control group and must be indistinguishable from the treatment being
tested. Giving a placebo to the controls ensures that any changes
we observe in the treatment group are not simply the result of their
beliefs and expectations or the extra attention involved in taking
part in the study, or other unexplained variables.
The best quality trials are double-blind, meaning both patients
(or, in the case of children with Autism Spectrum Disorder, their
families) and researchers are unaware of which treatment group a
patient has been assigned to until all the research results have
been collected and analysed. (In a single-blind trial only one of
these groups — usually the patients — is blinded to which intervention
they are receiving). Blinding is important even if you have an objective
outcome measure (such as a reduced cholesterol blood level with
a cholesterol-lowering medicine) but in the case of Autism Spectrum
Disorder, where you are going to be looking at subjective outcomes,
such as changes in behaviour, blinding is even more essential.
Why is blinding so important? Because when people participate in
research their beliefs and expectations that the treatment will
work can influence the results of the research quite significantly.
This is commonly referred to as the placebo-effect. Even the researchers
conducting the trial can fall victim to the placebo effect, although
in their case the correct term for it is observer bias. This is
not meant to imply that they set out to be deliberately biased when
they report their results. It just makes sense that if you have
a lot financially and emotionally invested in the research you are
more likely to believe that you can see a treatment effect.
So, in a randomised, double-blind, placebo-controlled trial (RCT)
the only difference between the two groups is the type of treatment
they receive. If the outcome between the two groups turns out be
significantly different it is reasonable to conclude that this difference
is caused by the treatment — cause and effect.
Non-blinded (or open label) studies have actually been found to
overestimate the effects of a treatment by about 17%. The effect
of randomisation is even greater; analyses have shown that non-randomised
studies may overestimate treatment effects by up to 40%!3 So, in
theory, an unrandomised, open-label study could overestimate the
effectiveness of a treatment by over 50%. That’s enough to make
an ineffective intervention appear effective.
It is still occasionally possible to get a false positive (ie showing
that a treatment is effective when it isn’t) or false negative result
(not showing a treatment is effective when it is) in a RCT; the
latter is especially likely if there are only a small number of
patients enrolled in the trial. The trouble with most clinical trials
in Autism Spectrum Disorder is that they do tend to be quite small.
That’s why we need the results to be replicated (or reproduced)
in more than one trial, ideally including patients of different
ages and severity (ie high- and low-functioning) so we can see if
the treatment is effective in a larger group of people with Autism
Spectrum Disorder. If a result is replicated several times over,
and these studies are published in reputable peer-reviewed journals,
you can be confident you are seeing a real treatment effect (or
not, as in the case of secretin, discussed below).
To overcome the problem of small patient numbers in clinical trials,
sometimes researchers perform systematic reviews or meta-analyses.
These are the absolute top of the evidence hierarchy. In a meta-analysis
data from several RCTs are pooled together and the results analysed.
The larger patient numbers means you may be able to pick up a treatment
effect that was not evident in the individual small trials. Only
good quality RCTs should be included in meta-analyses, otherwise
the results are pretty meaningless.
One of the best known producers of systematic reviews is the Cochrane
Collaboration. They have performed a number of systematic reviews
of Autism Spectrum Disorder treatments, which you can see yourself
at The Cochrane Library. An easy way to access the library is through
the Cochrane Collaboration website:
www.cochrane.org/
First click on the Cochrane Library link. Then it is fairly easy
to find these reviews using the search facility; otherwise you can
click on the link to Cochrane Reviews By Topic. The Autism Spectrum
Disorder reviews are located under Developmental, Psychosocial and
Learning Problems; select Developmental Problems then Autistic Spectrum
Disorder. Although these are quite technical documents, each review
has a plain English summary of its conclusions. We are fortunate
that all residents of Australia can access The Cochrane Library
for free, thanks to funding provided by the federal government.
Thus, when that specialist says there is ‘no
evidence’ for a particular treatment, it doesn’t necessarily mean
there is no research behind it. What it does mean is that we don’t
yet have any proof that it is effective. This may be because the
clinical research hasn’t been done yet, or sometimes because the
research has been done and the treatment hasn’t been found to be
effective.
The story of secretin — a case study in evidence-based health care
Secretin is a gastrointestinal hormone; one of
the hormones that control and regulate the digestion of food. It
became the focus of attention in 1998 when researchers at the University
of Maryland published a report of three children with Autism Spectrum
Disorder whose Autism symptoms improved after they received a secretin
infusion during an endoscopy. Following the publicity thousands
of children with Autism received intravenous secretin, resulting
in an international secretin shortage.
People started speculating on how secretin could
affect the symptoms of Autism. It was thought that secretin may
act as a neuropeptide (a type of chemical signal in the brain).
Secretin and its receptors have been found in the central nervous
system of animals, although the exact role of secretin in the human
brain is unclear.
Therefore there were both anecdotal reports that
secretin was effective and animal studies suggesting a theoretical
mechanism of action.
However, when researchers began conducting RCTs
of secretin in children with Autism Spectrum Disorder they were
unable to demonstrate any effect on Autism symptoms. In all, over
a dozen studies, involving over 700 children were conducted and
not one found that secretin was more effective than a placebo.4
Later in the chapter Dr Richard Couper proposes some theories to
explain why this occurred.
A Cochrane systematic review concluded that secretin
‘should not currently be recommended or administered as a treatment
for Autism’.5 Despite this, some of the parents involved in these
trials elected to continue secretin treatment even after being told
their child, according to all objective measures, had not responded,
illustrating the power of the placebo effect. Secretin is still
promoted as a treatment for Autism even today.
Sadly secretin did not turn out to be the ‘cure’
we all hoped. However, scientists are still continuing to investigate
the role of neuropeptides in Autism Spectrum Disorder.
Why do we need evidence-based treatments
On a societal level, governments like evidence-based
medical treatments because they provide them a more cost-effective
way of allocating health spending. Evidence-based medicine is also
behind many successful health promotion campaigns.
In Australia, the federal government makes sure that all procedures
and medicines it subsidises through Medicare and the Pharmaceutical
Benefits Scheme ‘are supported by evidence of their safety, clinical
effectiveness and cost-effectiveness’.6 This is as it should be.
I’m sure as tax payers you would prefer that your precious tax dollars
were not wasted on unproven treatments for say, diabetes or cancer.
The trouble is that the treatment of Autism Spectrum Disorder is
not generally known for its good evidence-base. In fact, it is the
very lack of evidence which causes some of the biggest arguments.
We have claim and counter-claim that a treatment is effective, or
not effective, but without good evidence we cannot always be sure
who’s right. Also the lack of good evidence makes it easier for
governments to justify not funding many Autism Spectrum Disorder
treatments. That’s why as parents we need to push for better clinical
research.
On a personal level, you might like to use evidence-based principles
to help you to decide what treatments to use with your child, especially
if your own financial resources are limited. This doesn’t mean you
have to completely disregard treatments without good evidence, but
we’d recommend you give priority to those interventions with better
quality research behind them.
What are the downsides of an evidence-based approach?
Well, in the first place, we cannot always conduct
clinical trials of the highest quality demanded by evidence-based
practice. We can conduct placebo-controlled trials to test the effectiveness
of medicines (conventional or complementary) in Autism Spectrum
Disorder but for obvious reasons we cannot have a placebo-controlled
trial of an educational intervention. We can have a control group,
however, (children receiving an alternative intervention; it would
be unethical to have a no intervention group these days) and some
of the recent trials of early intervention have even recognised
the importance of using randomised controls.
Also, it takes lots of time and money to conduct good quality research,
especially if we replicate the research several times over. Lots
of parents say, ‘but we can’t afford to wait for the evidence’ and
that’s a reasonable view. So, if you decide to use a non-evidence-based
treatment for your child, here are a few questions you might like
to consider before you commit.
What are the potential side effects or risks?
Does the theory behind the proposed treatment
make sense, given what we know about Autism?
Is it individualised, taking into consideration
my own child’s behaviours and symptoms?
Is it monitored for effectiveness (based on data)
and changes in dose and intensity?
What training and supervision are needed to administer
the treatment?
How much does it cost?
Prescribed medicines in Autism Spectrum Disorder
We haven’t yet found a medicine which can ‘cure’
Autism but sometimes medicines can help alleviate symptoms and manage
associated conditions, such as attention deficit hyperactivity disorder
(ADHD), anxiety, sleep disorders or obsessive compulsive behaviour.*
Some medicines which have been prescribed for people with Autism
Spectrum Disorder are discussed in Table 1. These medicines appear
to work by altering the level or response to important neurotransmitters
(serotonin, dopamine and noradrenaline) in the brain.
We need to avoid medicines becoming the ‘easy
option’ for managing some symptoms, especially in the case of antipsychotics
used to manage aggression, which is more common in low functioning
Autism. These medicines should really only be considered if behavioural
measures and environmental supports (such as PECSÆ or other visual
aids) have failed to bring the problem behaviours under control.
With this in mind, the atypical antipsychotic,
risperidone (RisperdalÆ) was recently listed on the Pharmaceutical
Benefits Scheme, but with some significant restrictions on its use:
Treatment under the supervision of a paediatrician or psychiatrist,
in combination with non-pharmacological measures, of severe behavioural
disturbances in a child or adolescent aged less than 18 years with
Autism. Behaviour disturbances are defined as severe aggression
and injuries to self or others where non-pharmacological methods
alone have been unsuccessful.7
However, in other cases medicines may help to reduce problems such
as hyperactivity, anxiety or obsessive compulsive behaviours, which
prevent a child succeeding at school or slow progress of their other
interventions. In these situations a carefully supervised trial
of a medicine may be justified.
Joe currently takes the stimulant medicine methylphenidate (RitalinÆ)
and whilst I was initially reluctant to go down this path, the benefits
for him (improved attention and therefore better performance at
school) do seem to outweigh the downsides (some initial insomnia
and appetite suppression.
1 Coleman, Mary. Ed (2005). The Neurology of
Autism, New York, Oxford University Pres.
2 Bandolier Evidence Based Medicine Glossary www.jr2.ox.ac.uk/bandolier/glossary.html
Bandolier – Evidence-Based Health Care (2001). Bandolier Bias Guide
www.jr2.ox.ac.uk/bandolier/Extraforbando/Bias.pdf
3 Levy, SE, Hyman, SL. (2005). Novel treatments for autistic spectrum
disorders. Mental Retardation and Developmental Disabilities Research
Reviews, 11, 131–142.
4 Williams KW, Wray JJ, Wheeler DM (2005). Intravenous secretin
for autism spectrum disorder. Cochrane Database of Systematic Reviews,
Issue 3. Art. No.: CD003495. DOI: 10.1002/14651858.CD003495.pub2.
5 Australian Government Department of Health and Ageing. Background
to the establishment of the Medical Services Advisory Committee
(MSAC) www.msac.gov.au/ .
6 Schedule of Pharmaceutical Benefits August 2007 www.pbs.gov.au/html/healthpro/search/results?term=risperidone&scope=PBS+STATIC&form-type=simple
7 Jesner OS, Aref-Adib M, Coren E. (2007). Risperidone for autism
spectrum disorder. Cochrane Database of Systematic Reviews, Issue
1. Art. No.: CD005040. DOI: 10.1002/14651858.CD005040.pub2.
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This information is reproduced with kind permission
from a chapter of The
Australian Autism Handbook published by Jane Curry Publishing
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