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Wednesday, 20 November 2019

Ordinary Gifted or Gifted with Asperger’s Syndrome? And Treatment options for Aspies



Asperger with his Little Professors

This blog is focused more on severe autism, but today it is turn for the Aspies.  The post does rather ramble, because I included some old unused material on micro-dose LSD that may be Aspie-relevant.

Most people diagnosed with autism these days do not have severe autism and so their ideal medical therapy may be very different to the Polypill, I developed for my son.

For a young Aspie he might just need a single intervention like Sertraline (Zoloft) and nothing else, or perhaps Amantadine.

There is more than twenty years of experience medically treating people with Asperger’s, but it very much remains a case of trial and error to find what works.

It does look like most translational research in autism is now focused on those without problems with speech or cognition. That is good news for people with Asperger’s, not so good for the other end of the spectrum.

The paper below is 20 years old, but the medical treatment has not become out of date.






Behavior Problems. Children with AS usually have some behavior problems. They may be compulsive or hyperactive. They may be prone to tantrums or aggressive outbursts. They may routinely hit other children without provocation or touch people in inappropriate ways. Some AS children suffer from anxiety attacks or specific phobias. They may be sensitive to teasing, but consistently demonstrate provocative behaviors that invite teasing. Some AS children will engage adults in endless arguments if given the opportunity. Parents especially may find themselves trapped in repeated discussions about the same events or disagreements. Adults should not attempt to reason for more than a minute with such children (Barron & Barron, 1992; Dewey, 1991; Klin & Volkmar, 1995). Brief, concrete directives are most effective. Visual supports like pictograms can be posted on a child's notebook, desk, or on the wall to visually cue the child regarding expected behaviors. The addition of visual supports can be remarkably effective in helping AS students organize their behavior. Teachers and parents should consult with an augmentative communication specialist to learn more about visual supports.

In addition to behavioral and educational approaches, medications may be helpful in treating specific problematic behaviors. Medications can significantly improve the quality of life of AS children when they exhibit compulsive or aggressive behaviors that interfere with school adjustment or family life. Medication may also be needed to alleviate symptoms of depression, thought disorder, or anxiety attacks. Tofranil and Prozac have been recommended (Grandin, 1992). Beta blockers have been helpful for some aggressive AS children, and Anafranil, Luvox, or one of the SSRIs (e.g., Zoloft) can be useful in reducing obsessive-compulsive tendencies (Gragg & Francis, 1997; Rapoport, 1989).

If you now look at what is recommend today, two decades later it is pretty much the same.

From the Kennedy Krieger Institute:

  
For core anxiety symptoms, her group listed four possible SSRI antidepressants, sertraline (Zoloft), Prozac, Celexa, or escitalopram (Lexapro). That listing was based upon data on children and teenagers who do not have a developmental disorder. The researchers noted that youth with autism often report one particular side effect with SSRI drugs: "behavioral activation," which may appear as hyperactivity, impulsiveness, or trouble sleeping.14 Other possible side effects, which are not unique to autism, are suicidal thoughts in adolescents, or worsening of mood problems in people with bipolar disorder. So these drugs "should be prescribed cautiously in youth with ASD, with close monitoring," the researchers advised. Their article, in the journal Pediatrics, includes starting and maximum doses for doctors to consider. (See Additional Resources below for a link to the article, to share with your health care provider.)

Over at the MIND Institute at UC Davis:-

Specifying and Treating Anxiety in Autism Research (STAAR) Study

At least 50 percent of children with autism spectrum disorder (ASD) exhibit clinically significant anxiety symptoms. These are associated with increased social deficits, depression, irritability, and stereotyped and self-injurious behaviors. While it is clear that anxiety represents a substantial problem for those with ASD, there are important issues that need to be clarified before effective treatment becomes widespread. This project of the ACE will explore better ways to detect anxiety in children with ASD and determine whether cognitive behavioral therapy or medication can better alleviate their symptoms

  
Studies often appear to show no benefit, but it depends what you choose to measure (the primary outcome) and how large the sample is.



At first, the fluoxetine group appeared to show a slight but significant easing of obsessive-compulsive symptoms after four months compared with the placebo. But after the researchers controlled for factors including age, sex and the severity of symptoms at the start of the trial, the difference vanished. Fluoxetine did no better than the placebo.
The relatively small sample size could have limited the researchers’ ability to detect a benefit from the drug, Neumeyer says. “It’s possible that, with higher numbers, they would’ve found subgroups who benefit from SSRIs,” she says. “That’s the painful part of this [kind of] research though; you’re left wondering.”

Interesting to see low dose Prozac (fluoxetine) used successfully in severe French autism:-

Low-Dose Fluoxetine in Four Children with Autistic Spectrum Disorder Improves Self-Injurious Behavior, ADHD-Like Symptoms, and Irritability


In this article, the authors present four clinical cases of ASD-diagnosed children with ADHD-like symptoms and/or SIB and/or other heteroaggressive behaviors and/or irritability and impulsivity. Each was treated with low doses of fluoxetine, specified as follows: 2.5 mg/d (liquid formulation) in the morning for the first week, followed by a flexible titration schedule based on weight and tolerability. The Hollander et al. protocol [3] is reproduced here, in which children with ASD were given low doses of fluoxetine. Patients were assessed using the Clinical Global Impression Scales (CGI) [12] during the time of fluoxetine introduction and observation. None had tried an SSRI treatment before the reported trial.

In conclusion, in these case reports, we found that the prescription of fluoxetine, in addition to valproate and cyamemazine (Case 1) or to risperidone (Cases 2, 3 and 4), could be effective on severe behavioral symptoms associated with ASD in children. It is important to inform child psychiatrists about this therapeutic possibility even if it would be difficult to predict the rate of responders on the basis of this cases and the literature. The role of comedication remains unanswered as none of our cases was on fluoxetine monotherapy.
  
Recall this old post:- 

When is an SSRI not an SSRI? Low dose SSRIs as Selective Brain Steroidogenic Stimulants (SBSSs) via Allopregnanolone modifying GABAa receptors and neonatal KCC2 expression




Micro-dosing LSD for Aspies?

Since we are on the subject of Aspies, I will insert a post that I never finished.  It is very much for the genuine Aspie, the one with a high IQ, the type working over at Google HQ. Usually male, does not strictly need any medical treatment, but may seek some out nonetheless.

Even though LSD was used at high doses in people with severe autism in the 1960s at UCLA, current interest involves micro-doses taken by people without any severe disability. 

A trial is about to start at Imperial College in London that may particularly interest Californian and Dutch Aspies.



Silicon Valley geeks say it sharpens their thinking and enhances creativity. Other people say it lifts the fog of depression. A novel experiment launching 3 September 2018 will investigate whether microdosing with LSD really does have benefits – or whether it’s all in the mind.
Microdosing using psychedelic drugs – either LSD or magic mushrooms – is said to have become very popular, especially with people working in the Californian digital tech world, some of whom are said to take a tiny amount one or more days a week as part of their routine before heading to work. It’s not for a psychedelic high, though – it’s to make them more focused.
Microdosers tend to use either tiny amounts of LSD – as little as one-fifteenth of a tab – or of psilocybin, the active ingredient in magic mushrooms. The study is recruiting just those who use LSD, because of the difficulty in disguising even ground-up mushrooms in a capsule.
But it’s illegal. So how many people are microdosing is unknown and there is only anecdotal evidence of the effects and any downsides. In a bid to learn more, the Beckley Foundation, which was set up to pioneer research into mind-altering substances, and the unit it funds at Imperial College London, will launch the first ever placebo-controlled trial of microdosing on Monday, 3 September 2018.

It will be unique, says Balázs Szigeti, the study leader. The cost and the illegality of LSD would make a conventional study prohibitively expensive. So he has hit on a way of running it by inviting those who already microdose to join a “self-blinded” study. They will take either what they usually use in a capsule or an identical dummy capsule instead, without knowing which is which. They will complete questionnaires and tests and play cognitive games online, and only at the end will they learn whether they were happy and focused because of LSD or because they thought they were using LSD.

Conclusion

The big difference between treating mild autism (Asperger’s) and severe autism is whether cognitive function is a target.  For severe autism raising cognitive function is the most important target, because it has the potential to improve all other behavioral issues. 

Aspies have been self-treating for decades and in some countries have a helpful psychiatrist happy to prescribe off-label (SSRIs, bet-blockers etc).  They often seem to like 5HT2A agonists.

The effective drugs for mild autism (Asperger’s) may have only limited value to those with severe autism.  Unless you resolve cognitive impairment, you will not transform the developmental trajectory.

It would be helpful if during the initial observational autism diagnosis, the doctor made clear to parents, what kind of autism the child has.   This often is not the case.

It is clear that most people diagnosing autism in very young children do not attempt to measure IQ, or even use an autism ratings scale, like CARS.  There are understandable reasons for this, but it still looks lazy to me.  Nowadays people struggle less hearing the word “autism”, but nobody wants to hear about MR/ID in their 3 year old.  So better to keep silent and avoid parents bursting into tears.

You really do need to be told where you are on the scale from Aspie to the other extreme of Autistic disorder/ Kanner’s/Classic/SDA.  You might think this would be obvious, but it is not.  If you have a 4 year old Aspie, start with Aspie therapies, not therapies for severe autism.

We saw in Catherine Lord’s study that all of those in her 20 year longitudinal study of children with an autism diagnosis, also had an IQ , when measured, indicating MR/ID.  Her study group was a random selection of those diagnosed with autism where she worked.  Back then autism meant autism.  Her “top performing” 40% have normal IQ as adults, but even in that group their measured IQ at age 3 or 4 was less than 70.  This group are not Aspies, they would have had normal/high IQ when tested at the age of 3 or 4.

The meaning of the diagnosis has changed so much in 20 years that the research now talks of autism with a developmental disorder and autism without a developmental disorder.

Actually, “autism” is supposed to be a developmental disorder; that was the whole point. But never mind.

Aspies have had a wide range of treatment options for more than 20 years and they also stand to benefit for the new generation of “autism” drugs, which are actually mainly for mild autism.

As with severe autism, treating an Aspie will also require personalized medicine, or just call it trial and error.  Prozac might be hopeless, but Zoloft work wonders.  ADHD meds might help, or just make things worse.  Oxytocin might improve empathy, or do absolutely nothing.  Perhaps the study at Imperial will show micro-dose LSD does have a benefit.  Since you are fully verbal and have a high IQ it is not hard to establish whether there is a benefit or not, move on and perfect your personal therapy.

It is the other end of the spectrum, where there is a big problem.  You may need to look at the new drugs being developed for Down Syndrome, Fragile-X and the numerous rare single gene autisms. Those drugs will not be cheap.






5 comments:

  1. I found this article on schizophrenia interventions pretty neat. Sure, it has some limitations, but you still would like to see something similar done to autism. The big difference is perhaps that though schizophrenia also is a multigenetic/epigenetic disease, it looks more homogenous than autism.

    Potentially repurposable drugs for schizophrenia identified from its interactome
    ncbi.nlm.nih.gov/pmc/articles/PMC6722087/

    /Ling

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  2. hi Peter, thank you for the hard work you put in this blog. Can you tell me the starting dosage for verapamil? I have child 13 year old with classic autism, recent pans/pandas flare, prior to this complaint, sweet and now turned into an adolescent that I do not recognize...we are on the long road looking for solutions for PANS.. but want to start some things. I have migraine, and thought verapamil might be a good solution and we do not need electrolte monitoiring like in bumex. thank you again.

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    Replies
    1. 20-40 mg of verapamil three times a day seems to work for a sub-set of autism. In responders the effect comes very quickly, you will know in a day or two.

      Electrolyte monitoring is not so complicated. Many people (70+%) will just do it once to check all is OK. Bumetanide is the cognitive game changer.

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    2. Do children on verapamil need heart rate momitoring and /or blood pressure?

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    3. Care has to be taken with all drugs and supplements. The drugs discussed in this blog are among those that can generally be safely used long term, but that does not mean that adverse reactions cannot occur.

      Many drugs used off-label in autism can lower blood pressure but it is easy to monitor blood pressure.

      Ideally you go to your autism doctor and he/she monitors the situation for you. If you get bumetanide or verapamil from a pyschiatrist they will not have experience of electrolytes etc.

      For many people the situation is far from ideal.

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