Asthma-Autism Hypothesis and Immunomodulatory Therapy for Autism

You may be aware that about a third of people with autism also have asthma; this is not a coincidence, just as the finding that autistic people have elevated cholesterol was not a coincidence. 

Since Monty, aged 10,  has both autism and asthma, I have had to become informed on both conditions.  Having now read the research on both autism and asthma, it is somewhat shocking that there are so  many parallels.  I would now go so far as to make my own hypothesis:-

The causes of Autism and Asthma are overlapping; so much so, that some drug treatments for the core symptoms of one may be effective in the other.

This may sound a strange, even bizarre proposition, but I will show that it is at worst plausible and at best proven.  Note that it was the observation that bumetanide was an effective treatment in neonatal non-convulsive seizures ,that led to the idea of trialling that drug on autistic children.  Many children with autism subsequently develop epilepsy or other forms of seizure.  So investigating the so-called comorbidities is not such a novel idea.
 

Drugs effective in both Asthma & Autism

·         NAC (N-acetyl cysteine) – reduces oxidative stress

·         Prednisone – powerful steroid for short term use to supress immune system

·         Statins – reduce neuroinflammation

·         Ketotifen – mast cell stabilizer and anti-histamine

In case you are not familiar with asthma, there are some remarkable similarities between asthma and autism, just take a look:-

·         Both affects boys much more than girls

·         Both involve neuroinflammation

·         Both are linked to defects in the auto-immune system

·         Exact cause of both is not known, but is seen as a combination of genetic and environmental factors

·         Both were thought of as a psychological disorders and were unsuccessfully treated as such

·         Both are usually lifelong conditions, though functional recovery is much more common with asthma than autism, often occurring after puberty with asthma

·         In recent decades there has been an “epidemic” increase in prevalence of both. 

Asthma is much more prevalent among those with autism the general population and is frequently cited as a comorbidity, along with epilepsy and GI disorders.

Left untreated, asthma can easily be fatal, so it has been well studied and numerous drugs have been specially developed.  I thought that perhaps there are insights for autism to be gained by looking at how asthma is treated;   indeed there are.

Asthma Prevalence

There is a lot of research into the prevalence of asthma.  After increasing for several decades, there are some reports of it plateauing or even declining.

Is the prevalence of asthma declining? Systematic review of epidemiological studies

 

It is generally accepted that asthma is a disease of the developed world and the apparently the English-speaking world in particular.

Asthma Statistics

The American Academy of Allergy Asthma & Immunology (AAAAI) has an eye-opening summary of asthma statistics showing:-

·         The prevalence of asthma in different countries varies widely, but the disparity is narrowing due to rising prevalence in low and middle income countries and plateauing in high income countries.

·         An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths attributed to the disease.

·         It is estimated that the number of people with asthma will grow by more than 100 million by 2025.

·         Workplace conditions, such as exposure to fumes, gases or dust, are responsible for 11% of asthma cases worldwide.

·          About 70% of asthmatics also have allergies.

·         Approximately 250,000 people die prematurely each year from asthma. Almost all of these deaths are avoidable.

·         Occupational asthma contributes significantly to the global burden of asthma, since the condition accounts for approximately 15% of asthma amongst adults.
 

Asthma Treatment

To learn more about asthma and how it is treated the University of Maryland have a helpful summary, just click the link.

There are generally three lines of treatment.  The well-known first line of treatment is the “rescue” inhaler that children are seen with at school, this is to treat acute attacks.  These are bronchodilators, like Ventolin, that open the airways in moderate to severe attacks.

If acute attacks become frequent, then typically an anti-inflammatory steroid inhaler is prescribed.  Long-term control medications are essential to minimize long-term damage of the inflammatory response, to reduce the risk of serious exacerbations.  This is used daily in the hope of preventing future attacks.

In case of an acute attack that does not respond to the rescue inhaler, an oral corticosteroid can be given .  These are powerful drugs that because they are administered orally will affect the whole body;  the steroid inhaler substantially avoids this drawback.  The corticosteroid  works by deactivating the immune system.
 

There are many other therapies used by allergists, in particular the use mast cell stabilizers and anti-histamine drugs.

Ketotifen

Ketotifen is mast cell stabilizer, which means it blocks mast cells from releasing histamine it is also an H1 antagonist, which means it blocks H1 histamine receptors.  It is primarily used as a long term treatment of asthma.  It will not stop an acute asthma attack, but it should reduce their frequency.  If given to high risk children, its use can avoid the initial onset of asthma.

Prevention of asthma by Ketotifenin infants with atopic dermatitis.

It is used in irritable bowel syndrome and it is by DAN doctors to treat GI problems in autism.  If have read about mast cells and Dr Theoharides, then you can see how mast cells may play a key role in autistic behaviour and as such Ketotifen could be a prime therapy.

Autism and the auto immune system

There is a substantial body of opinion that autism is itself a disease linked to the auto immune system, like asthma and indeed type 1 diabetes.  The over active immune system is destroying certain important body functions.

The logical conclusion would be to find a way to down rate the immune system so that the unwanted affects were minimized, without leaving the body open to attack.  This strategy is indeed followed in asthma therapy where the emergency treatment is oral corticosteroid Prednisone

If all this sounds familiar, it should do.  The hygiene hypothesis has also been used to  link asthma, autism and the overactive immune response. 

In the case of autism at least one therapy is also based on this approach.

There is the case of Stewart Johnson in America, who trawled through the research looking for ways to help his autistic son.  He became convinced that the immune system was the key and looked into ways to down rate it.  He came upon the idea of using the TSO parasitic worms.  These parasites live in pigs(?) and in order to preserve themselves they evolved a method of reducing the immune system of their host so that they would not be expelled.  Treatment with such worms has been tried with other conditions, such as Crohn’s disease.  Mr Johnson ordered some TSO from Germany and fed them to his son.  He found that initially there was no impact on his son’s autism, but when he increased the dose there was a marked reduction in autistic behaviours.

Every couple of weeks or so, he gave his son another dose of TSO.

A clinical trial is being carried out at the Albert Einstein medical school to test the effectiveness of the treatment.  Mr Johnson created a website to document his experiences.  

It appears that not all people with autism respond to TSO; perhaps this is not surprising, not all people with autism have asthma either.

Perhaps Mr Johnson should see if a mild dose of Prednisone has the same effect as the worms?

Prednisone & Autism

It turns out that some doctors have indeed been prescribing prednisone for autism.  Most are DAN doctors, but not all.

You will even see on autism forums that when kids were given prednisone for their asthma, they suddenly had a big improvement in their autism.

http://www.autismweb.com/forum/viewtopic.php?p=109879

http://www.autismweb.com/forum/viewtopic.php?f=4&t=30238

While extended use of steroids causes side effects, it seems some doctors used them to try to proactively reverse regressive autism and to get non-verbal kids to speak.  This would seem entirely logical.

Immunomodulatory Therapy in Autism

An truly excellent review paper of Immunotherapy in Autism has been written by Dr Michael Chez, a respected mainstream specialist from Sacramento.  He also seems to be endorsing the use of the prednisone steroid in autism therapy

Immune Therapy in Autism: Historical Experience and Future Directions with immunomodulatory Therapy

 Here are two important paragraphs:-

Experience with EEG abnormalities and autistic regression cases that respond to steroids have been described in various case reports. Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week. Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner.

 

In summary, among the current studies of immune targeted therapies, the most collective data on steroid effects on autism is probably the largest. Clear clinical improvements are consistent between different groups that had peer-reviewed assessments. In addition, all reported similar outcomes and side effects were made with the use of steroids. As in IVIG treatment, there has been no report of cure or elimination of all autism features. In the majority of cases, steroid effects did not permanently alter an autism diagnosis in these patients. Clinical concerns about steroid dependency and side effects, such as Cushingoid or long-term, well-known steroid effects have limited more randomized or controlled studies of steroid medications in autism. This is unfortunate, as there may be a potential for significant improvement from steroid treatment on cytokine and chronic immune dysregulation in autism.

Oxidative Stress, Nitrative Stress and Inflammation in Asthma

Much has been written about oxidative stress and inflammation in autism, well it turns out these are key issues in asthma.  In asthma, fortunately, they have been looked into very seriously and all is well documented.

Another superb paper, this time by Professor Peter Barnes, from Imperial College in London is:- 

Histone acetylation and deacetylation: importance in inflammatory lung diseases

 This paper should be read from cover to cover, it is full of interesting information.  For example cigarette smoking in asthma causes oxidative stress.  That stress continues even after the patient has given up smoking, so it is chronic.  To treat this oxidative stress, guess what? He uses NAC just like I using for oxidative stress in my son’s autism.

Also, oxidative Stress causes steroid resistance, so steroids that work in asthma do not work well in COPD.

Cytokines in asthma

Because asthma affects so many people and can be fatal, there is a considerable research effort and drug pipeline.

Cytokines play a key role in all inflammation.  The keys ones have been identified in both autism and asthma; the difference is that in asthma they are being studied in great detail.

Also several cytokine modulators are in various stages of development, but tested on asthma sufferers.
 

For the scientists among you, this subject is covered in depth by Professor Barnes, from Imperial College.

The cytokine network in asthma and chronic obstructive pulmonary disease

How Corticosteroids control inflammation

If you are tempted to make a trial of Prednisone, then you should be interested a read how such steroids control inflammation.  Here is an excellent paper that explains how corticosteroids control inflammation:-

How corticosteroids control inflammation: Quintiles Prize Lecture 2005

 

Asthma and statins 

I have established that the anti-inflammatory properties of statins, already applied neuroscientists in other fields, are very helpful in treating autism.

Researchers are also looking to see whether these properties of statins can be helpful in treating asthma.  Here is a recent paper:-

Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis

The paper concludes -

The findings suggest beneficial effects of statins in asthma management.

 Yet again the same drug has a positive effect in both conditions.

Conclusion

If you have made it this far in my post, congratulations!

So far from asthma, the autism world has taken Prednisone, Ketotifen and NAC.  I suspect that as new anti-inflammatory drugs are developed for asthma, other little gems will become available.  Also new stronger anti-oxidants are likley to be developed for asthma, since they find NAC not powerful enough. 

Prednisone clearly has drawbacks, but in the case of a sudden regression in autism, it might well be a very smart short term intervention.  Perhaps also in kick-starting development where it has stalled/plateaued.

Quite remarkably, statins not only reduce autistic behaviours but also help control asthma.

I think I have proved my hypothesis

The causes of Autism and Asthma are overlapping, so much so, that some drug treatments for the core symptoms of one may be effective in the other.

Also, we learned from Professor Barnes that corticosteroids do not work well in the presence of oxidative stress.  In asthma he reduces this stress using NAC; I do the same in autism with NAC.  This means that if you are going to trial prednisone, it would be very wise to start with NAC first.  It also means that if your child has both autism and asthma, their inhaled steroid will work better if you  are also using both NAC and statins.   

In case you were wondering, prednisone, Ketotifen and statins are all off-patent and very cheap.  NAC is an OTC supplement and inexpensive if you buy it online.


 

Autism flare ups and comorbidities

Anyone familiar with autism will know that it seems to go in waves of good and not so good.  Generally this gets accepted as just the way it has to be.

I chanced upon an unusual paper recently, it was all about comorbidities in autism.  As you may know, comorbidities are other diseases that seem to frequently occur alongside autism.  The main point of the paper and the charity behind it, is that comorbidities should be diagnosed and treated, rather than ignored, just because the person has ASD.

The paper was produced by Treating Autism, a UK charity that follows a biomedical approach similar to the American DAN organisation.  They have a link to a very comprehensive summary of what DAN actually recommends. The DAN paper is by a Dr Jepson.

The idea of treating the comorbidities as they crop up, seems entirely logical to me; but it seems to miss the bigger issue of what the comorbidity might help tell us about the autism itself.

Their list of comorbidities to keep a look at for:-

·         Allergic disorders in ASD: effects of allergies on behaviour, cognition and anxiety. Food and inhalant allergies, allergic rhinitis.

·         Autoimmunity in ASD. 

·         Autonomic nervous system dysfunction (dysautonomia) in ASD

·         Seizure disorders in ASD

Allergic rhinitis was of course the one that caught my eye.  This is the medical name for the itchy red eyes and runny nose caused by summertime pollen and pollution.  This reinforced by own observation that histamine can have a major negative impact on behaviour in ASD.  This was presented in my recent posts on histamine and antihistamine drugs.

Also of note to me was the observation that atopic dermatitis (itchy skin) and asthma are comorbidities.  Asthma was one of the comorbidities I choose to investigate myself.  An interesting observation I came across was that atopic dermatitis is actually a good predictor of developing asthma and, in fact, that by effectively treating it with a particular drug (ketotifen), you can actually halt the progression to asthma.  There is a study investigating exactly this issue; one half of the trial were itchy toddlers with a placebo and the other itchy toddlers had ketotifen.  A year later the group with ketotifen had a far lower percentage that had developed asthma than the placebo group.  I call that interesting but how many family doctors, let alone parents, are aware of that?

 Prevention of asthma by ketotifen in infants with atopic dermatitis

Also, another interesting paper all about childhood allergies is called The Allergic March.

Conclusion

Autism flare ups seem to be common and a little investigation may well lead to a better understanding of your child’s type of autism.  By recording data on bad behaviours, as in an ABA programme, or my preference, by just be keeping a watchful eye, you may well identify the cause and then find a remedy.  It might be a wobbly tooth, or it might be something more subtle like histamine.

I also believe that a detailed understanding of the comorbidities will ultimately lead to some effective therapies for autism itself.  Since it is clear that different people have different types of autism, knowing what triggers your child's flare ups may well help define what type of autism he/she has and therefore what therapies may or may not prove effective.

Histamine, allergies and reducing challenging “autistic-like” behaviours

Having recently discovered that an anti-histamine drug like Claritin can markedly reduce autistic behaviours, I have been looking into exactly why this might be and to see if there could be any other related interventions.  Here are the results and they pull together all sorts of related comorbidities and in the end I seem to have found a better solution for managing summertime autism flare-ups.

Allergies have long been linked to aggressive behaviours

It seems to be well known among allergists, that children with allergies may exhibit challenging behaviours.  It goes beyond the simple fact that the child with an allergy will be irritable and therefore behave badly; the allergy itself is affecting the behaviour.  Allergies tend to worsen behaviour and the science can explain exactly why this happens.   This applied to pollen type allergies, food allergies and even asthma.

In the case of asthma, I found several studies, one is called:  Prevalence of Behavior Problems in US Children With Asthma

The study concluded with:

Clinicians caring for children with asthma and their families should be aware of the relationship between asthma and emotional and/or behavioural problems and anticipate that a substantial number of their patients may have mental health services needs.

One alternative health website, gives a list of symptoms they believe histamine allergies produce in kids with ASD.

Some different types of responses to histamine seen in ASD children: If histamines become too high, you can see hyperactivity, compulsive behaviors, depression, abnormal fears, intense mood swings, runny nose, itchy eyes, sneezing, perfectionism, strong wills, explosive anger, anxiety, hair pulling, lack of focus, scripting (repeating commercials or television programs, etc.), high libido, giggling (which can be a sign of yeasty behaviors), aggression, change in bowel movements, a craving for salt, frequent urination and rashes. Those who have seasonal allergies tend to see a worsening of these symptoms during spring time.

 What I recently noticed in Monty, aged 10 with ASD, were some of these behavioural problems, but  with only the slightest outward sign of an allergy.

Food allergies causing autism-like behaviours

I was surprised to find one allergy site listing the behavioural effects of food allergies, it reads like a long list of autistic behaviours.  This made me wonder if many of the milder cases of autism and the so-called autism epidemic may just be unresolved food allergies.  Many of the DAN interventions are about “healing the gut”, so maybe they are really more about treating food allergies.  Many cases of classic autism appear to have no problem with their digestive system at all.

Here is a list of behaviours from one site on food allergies:

 • Poor coordination

• Trouble communicating

• Self-destructive behavior

• Staring

• Difficulty in group games or sports

• Obsessions

• Nonsense talk

• Inability to read tones of voice and/or body language

The best studied/documented allergies

Asthma is the best researched allergic condition that I found, followed by food allergies and the rare condition of mastocystitis; this condition is rare but sufferers write extensively about it on the internet.  They also report on the effect of different drug combinations in managing their conditions.   Mastocystitis is also a comorbidity of autism that has been researched by Theoharides, who proposes his NeuroProtek supplement.

The result is that there has been a great deal of research and many established drug therapies exist.  The link between allergies and behaviour was investigated in the 1980s, but there has not been much written since, which is a pity.

Mastocystitis

The Mastocystitis Society of Canada have a good website.  It defines Mastocytosis as a myeloproliferative neoplastic (mpn) stem cell disorder, caused by an over-abundance of good immune system cells called mast cells and the release of mast cell mediators.

What that really means is that when the mast cells encounter an allergen they overreact and release too much histamine and also inflammatory messenger, such as cytokines.  These chemical disperse throughout the body.  The histamine activates the four types of histamine receptors around the body.  The pro inflammatory cytokines react in a different way, but promote an excessive inflammatory response.

To grossly simply the condition, mastocystitis is an extreme form of allergic response.

Mastocystitis is a comorbidity of autism and the mast cell response has been proposed to be a key part of autism.  It is interesting to look at how mastocystitis is treated.  Click the link here.

Note the use of both H1 and H2 histamine antagonists, many asthma drugs including the steroid Prednisone, and the mast cell stabilizer Ketotifen.

Histamine & Histamine Antagonists

 Histamine is a chemical in your body with three distinct functions:-

1.       Histamine triggers the inflammatory response

2.       Regulates physiological function in the gut

3.       Acts as a neurotransmitter

Most histamine in the body is generated in granules in mast cells or in white blood cells called basophils. Mast cells are especially numerous at sites of potential injury — the nose, mouth, and feet, internal body surfaces, and blood vessels.

Histamine functions in coordination in 4 types of receptors (H1, H2, H3 and H4).  In the central nervous system H1 and H3 receptors.  H1 is involved in allergies and asthma.  H2 is mainly involved invasodilation and gastric acid secretion.  H3 controls neurotransmitter release (histamine, acetylcholine, norepinephrine, serotonin).  H4 Plays a role in chemotaxis.

Histamine antagonists are drugs that inhibit the action of histamine by blocking specific receptors in specific parts of the body.  The most common drugs are H1 antagonists that block the H1 receptor in summertime allergies.  H2 antagonists reduce gastric acid secretion to heal peptic ulcers.

Histamine is the link between allergies and behavioural change

Histamine in the brain has been shown to directly influence behaviour (see later in this post for links).  There is also plenty of anecdotal evidence from allergists, as shown earlier in this post.

In addition histamine has been shown to weaken the blood brain barrier.   This would then let into the brain pro-inflammatory agents that might then cause a spike in neuroinflammation and oxidative stress.  This in turn leads to more challenging behaviours.   

The disruption to the BBB can be best reduced by the use of H2 antagonist. H1 antagonists have a much smaller effect.  See this study, which concludes:

 It is concluded that histamine causes an increase in blood-brain barrier permeability which is mediated via endothelial H2 receptors,

Ketotifen

Ketotifen is an H1 histamine antagonist.  It is a 40 year old antihistamine drug that is available over the counter in Europe.  Not only can it be used to treat  allergies (it is the active ingredient in many eye drops) and help control asthma, but it has some additional benefits.  It acts as a mast cell stabilizer, reducing the amount of histamine released by the mast cells when they encounter allergens.  It is the only  H1 histamine antagonist that does this.  In  addition it also blocks H1 receptors like the other widely used H1 histamine antagonists.
It is also used by body builders.  They are using another asthma drug called Clenbuterol.  This drug has the side effect of reducing your body mass index (BMI), so it makes you more muscular if you take enough of it for long enough.  Such use of Clenbuterol has side effects, the body builders are using Ketotifen to reduce these and allow them to use Clenbuterol for longer.  The misuse of Clenbuterol  affected beta-adrenergic receptor functions, for those who are curious.  Ketotifen blocks this from happening.

Celebrities, like a certain very well-known footballer’s wife, take Clenbuterol to stay thin.  Maybe they also take Ketotifen?

Ketotifen is extremely cheap and widely available in Europe and Canada.  In the US it is much more difficult to get hold of and so seems to have great rarity value.

In the US, some DAN doctors give Ketotifen to autistic children as a therapy for Gastrointestinal problems.  The well-known DAN doctor, with an audio lecture on this subject, states that Ketotifen is “mainly active in the gut”.  He obviously has not read the research, since the opposite is actually true.  Based on my limited research, it appears that some of these kids may just have autistic-like symptoms causes by the excess histamine in their brain. In other words they may just have a case of food intolerance / Irritable bowel syndrome rather than autism.  That would certainly be a relief to the parents concerned.

Other H1 Antagonists

You will know these drugs by their brand names :  Claritin, Zyrtec, Benadryl, Allegra, Phenergan etc.  There are several types of these drugs.  The early examples passed into the brain and so made people drowsy.  The second generation are the current big sellers, based on their non-drowsy effect.  When you dig deeper, you will see that they are all slightly different, and some work better than others in different people.  They also vary in which part of the body they have the most affect.

The older types are off patent and sold cheaply as generic over the counter drugs.

Mast cell stabilizers and irritable bowel syndrome

It has been long known that certain drugs reduce the allergic reaction in food intolerance.  Remarkably the same drugs are today also used to treat asthma.  The expensive drug I was prescribed as child called Intal (Cromoglicic acid) for food intolerance, is today called a mast cell stabilizer and  used in asthma therapy.

Mast cell stabilizers prevent the release of inflammatory chemicals like histamine from mast cells.

Another insight courtesy of the Mastocystitis Society of Canada:-

“Mast Cell Stabilizers - Ketotifen is preferred as most effective for entire body, Cromolyn mainly targets gastrointestinal system”

So it looks like the DAN doctors have chosen the wrong treatment for their GI problems, they should be using Intal not Ketotifen.

Modern second generation anti-histamines do not enter the CNS

First generation H1 antagonist crossed the blood brain barrier and had a sedative effect, making sufferers drowsy.  As a result there was a big search made of drugs that could relieve allergy symptoms but not make sufferers drowsy.  These second generation drugs are the current big sellers, although the first generation drugs are still widely available.

These modern drugs should therefore have less impact on histamine driven challenging behaviours than the old ones.

Most anti-histamines block the receptor rather reducing the amount of histamine

The popular H1 antagonist like Claritin do not reduce the amount of histamine produced in the body, they rather block the receptors used to detect it.  The amount of histamine flowing through your body remains the same.  That histamine weakens the blood brain barrier, allowing in things that might be better kept out.
It turns out that the H2 antagonists can reduce this degradation of the BBB, but H1 antagonists like Claritin have only a marginal effect.  This is all based on research in rats.

Sufferers of mastocystitis take copious amounts of H1 antagonists and H2 antagonists plus a whole host of other drugs.  H2 antagonists are old drugs like Tagamet, that were designed to reduce acidity in your stomach for treating ulcers and GERD.  It appears that also have unforeseen effects in your brain and elsewhere.

Histamine in the Brain

For those scientists among you, the areas to read up on are mast cells and how histamine functions in the brain.  Many of the papers on histamine in the brain are not available without payment.  Here is a short paper that is available.

The histaminergic system in brain: neurophysiology

Other good ones, not available free include:

The physiology of brainhistamine

and from way back in 1988:- 
Behavioral effects of histamine and its antagonists: a review

Research studies in to the use of H1 and H2 antagonist in autism

I was pleased to find that I was not the first to look into the use of histamine drugs in autism.  I did find two studies, and both were positive.  It is strange that in the 12 years since these studies were carried out, the research effort has not been followed up.

From my recently acquired insight, the H1 antagonist improved behaviour by blocking some of the unwanted response to histamine in the brain and the H2 antagonist help restore the blood brain barrier and keep out those unwanted pro-inflammatory agents like cytokines and perhaps even some histamine.

Niaprazine in the Treatment of Autistic Disorder  (H1 antagonist)

Abstract

Niaprazine is a histamine H₁-receptor antagonist with marked sedative properties. It has been employed in subjects with behavior and sleep disorders. No data concerning the use of niaprazine in subjects with autistic disorder are reported in the literature. The authors performed an open study to assess niaprazine efficacy in a sample of 25 subjects with autistic disorder and associated behavior and sleep disorders. Niaprazine was administered at 1 mg/kg/day for 60 days. A positive effect was found in 52% of patients, particularly on hyperkinesia, unstable attention, resistance to change and frustration, mild anxiety signs, heteroaggressiveness, and sleep disorders. Statistical comparison between responders and nonresponders showed no influence on niaprazine effect by age over or under 12 years, presence of neurologic signs, epilepsy, or abnormalities seen on brain imaging. Niaprazine was more efficacious in subjects with a mild or moderate degree of mental retardation. No side effects were observed. Because of its sedative effects and good tolerability, niaprazine can be used as a first-choice drug to improve behavior and sleep disorders in patients with autistic disorder. (J Child Neurol 1999;14:547-550).

 Famotidine treatment of children with autistic spectrum disorders: pilot research using single subject research design.  H2 receptor antagonists

Abstract

Using single subject research design, we performed pilot research to evaluate the safety and efficacy of famotidine for the treatment of children with autistic spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years old, with a DSM-IV diagnosis of a pervasive developmental disorder, living with their families, receiving no chronic medications, and without significant gastrointestinal symptoms. The dose of oral famotidine was 2 mg/kg/day (given in two divided doses); the maximum total daily dose was 100 mg. Using single-subject research analysis and medication given in a randomized, double-blind, placebo-controlled, cross-over design, 4 of 9 children randomized (44%) had evidence of behavioral improvement. Primary efficacy was based on data kept by primary caregivers, including a daily diary; daily visual analogue scales of affection, reciting, or aspects of social interaction; Aberrant Behavior Checklists (ABC, Aman); and Clinical Global Improvement scales. Children with marked stereotypy (meaningless, repetitive behaviors) did not respond. Our subjects did not have prominent gastrointestinal symptoms and endoscopy was not part of our protocol; thus, we cannot exclude the possibility that our subjects improved due to the effective treatment of asymptomatic esophagitis. The use of famotidine for the treatment of children with autistic spectrum disorders warrants further investigation.

Conclusion

Several important conclusions can be drawn based on a few hours of research on Google Scholar.

·         Your child may be subject to an allergic response that is outwardly hardly visible

·         The allergic response may be visible first as challenging autistic-like behaviour, rather than sneezing, runny nose, red eyes or wheezing

·         H1 antagonists can supress both the autistic-like behaviours and the typical allergic reactions

·         People do not all react the same way to H1 antagonist drugs.  A little experimentation is in order.  A drug that should work 24 hours can be effective for only 4 hours.

·         To avoid excessive use and possible side effects, allergists often combine different H1 antagonists, even though the information from the drug firm warns not to do this.

·         In some people the old H1 antagonists, that make you drowsy, work better than the new 2^nd and 3^rd generation drugs.

·         One old H1 antagonist called Ketotifen, seems to work wonders for some people.  It is both a mast cell stabilizer and a histamine receptor blocker.

I have ended up with a combination of Ketotifen and Claritin.  Claritin has an effect on behaviour within 20 minutes, Ketotifen had no apparent impact in the short term whatsoever.   You cannot keep giving Claritin every 4 hours.  It is supposed to be 10ml per day.

The day after taking Ketotifen things did change, and without having to overuse the Claritin.  The allergy is still mildly visible, but the challenging behaviours have gone.

I wish I had known about this last summer.  When Monty was aged 9, he went completely berserk on an aircraft and so as to restrain him, I was almost sitting on top of him, holding arms, legs and head; the flight attendant was asking if he would like a glass of water.  This year I will be well prepared with my Ketotifen/Claritin combo and anticipate no such problems.



Related Post:-

More on anti-histamines in Autism and introducing H4