Fine tuning Social Behavior in Autism with an existing pediatric drug, Desmopressin?

 

There are two closely related hormones, vasopressin and oxytocin, that have been extensively researched in autism. 

With oxytocin you can modify social-bonding behavior. You can increase oxytocin in the brain either via a nasal spray containing oxytocin, or you can add a specific bacterium to your gut that triggers a signal to the brain to produce more of its own oxytocin.  The latter is my preferred method, because you can produce a mild long-lasting effect throughout the day.

Oxytocin has a very short life and it does not cross the blood brain barrier.

There is even a new study in the works that will compare these two methods of treating autism.

 

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients.

Methods

This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0–24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13–24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24.

Discussion

This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients. 

My conclusion was to add two drops of L.Reuteri DSM 17938 (Biogaia Protectis) into the liquid part of my son's Polypill therapy. That way there are no extra pills to swallow and in theory the bottle should last 50 days, so I am not forever looking to buy more.  If you want a bigger effect, just add more drops.  The producer suggests a daily dose of 5 drops for babies, to promote GI health - the original intended purpose.

When it comes to Vasopressin it looks like you cannot avoid a nasal inhaler, unless you want to try transcutaneous electrical acupoint stimulation (TEAS).  There is a debate as to whether Vasopressin and its analogs (man-made modified versions) can cross the blood brain barrier and to what extent. 

There are 4 previous posts that looked at Vasopressin. 

https://epiphanyasd.blogspot.com/search/label/Vasopressin 

The Vasopressin showing good results in the trials at Stanford is the injectable pharmaceutical version of the hormone made into a nasal spray.  This kind of spray could be made easily at a compounding pharmacy.

It turns out that a synthetic analog of vasopressin, called desmopressin, has been widely used for over 40 years to treat nocturnal enuresis (night-time bed-wetting) among other more serious conditions.

 

Desmopressin in Autism 

“Nocturnal enuresis is common in individuals with but to our knowledge, there are no reports that desmopressin enhances social functioning in ASD (or in any other clinical population). This may be because desmopressin is typically administered at bedtime (so prosocial effects would be less evident) and orally (oral desmopressin does not cross the blood-brain barrier). The most likely explanation, however, is that desmopressin acts selectively on AVPR2, rather than on AVPR1A”

 

From:

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

 

Desmopressin N=1 example 

I was recently contacted by the father of a young boy with autism who has been prescribed Desmopressin nasal spray by his neurologist.

The father noted major positive behavioral changes from the first dose.

This is of course great news.

Desmopressin is a widely available drug, seen as safe, and that is why it is prescribed to children.

In the US the nasal spray version is no longer widely used for children and they use the oral version.

In some countries it is used for people with MS (Multiple Sclerosis) with nocturnal enuresis.

 

Desmopressin Shortage

Before readers get too excited, Ferring Pharmaceuticals, the big producer of Desmopressin nasal sprays did voluntarily withdraw its brands (Minirin, DDAVP Nasal Spray, Desmopressin Acetate Nasal Spray) from the market in August 2020 due to a quality problem. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetate

  

There is now a shortage and so what was an easy to obtain drug, may be more difficult to get.  There is a Pfizer version called Presinex.  

From the above paper on vasopressin for autism:-

Vasopressin benefits 

“In conclusion, the present pilot study determined that 4-week intranasal AVP treatment compared to placebo enhanced social communication abilities, diminished anxiety symptoms, and reduced repetitive behaviors in children with ASD. On nearly all behavioral measures, participants with the highest pre-treatment blood AVP concentrations benefitted the most from AVP treatment, suggesting that pre-treatment blood AVP concentrations may be useful for setting dosing guidelines for this medication. Last, intranasal AVP treatment was well tolerated with minimal side effects in this pediatric study population. These preliminary findings suggest that intranasal AVP treatment has potential to enhance social abilities in an ASD patient population characterized by currently intractable social impairments” 

Transcutaneous electrical acupoint stimulation (TEAS) to raise vasopressin 

“there is evidence that nonpharmacological interventions may facilitate endogenous AVP release, for example, electroacupuncture stimulation increases brain AVP concentrations in rats. Transcutaneous electrical acupoint stimulation (TEAS) therapy improves social functioning and anxiety symptoms in children with ASD, particularly in those with the largest post-treatment increase in blood AVP concentrations. The authors of this prior report theorized that increased AVP signaling may be the mechanism by which the prosocial and anxiolytic benefits of TEAS treatment were achieved” 

 

Vasopressin with Bumetanide  - take great care

A while back, one reader did ask me about taking intranasal Vasopressin with Bumetanide.  His doctor in California thought this might not be wise since the two drugs have opposing effects.

·        Bumetanide (a diuretic) makes you pee more.

·        Vasopressin (the anti-diuretic hormone) makes you pee less.

The real problem is the risk of low sodium, hyponatremia.  This is always a risk with vasopressin and the risk might well increase if you took Bumetanide.  The risk is going to be dose dependent.

If you take Vasopressin and then drink large amounts of water this will disturb the volume of fluids in your body and in particular it will lower the level of sodium.  This may lead to seizures and ultimately worse.

Bumetanide does disturb the level of electrolytes, but nearly all the change usually occurs in Potassium, this is why you need to add back potassium via diet and add a supplement.  Sodium is not normally a problem, but always check all electrolytes when taking a blood draw.

If someone adds vasopressin to their existing bumetanide therapy, the doctor should definitely monitor the level of sodium.

In most people’s diet, sodium is one thing you are likely to have too much of and it is very easy to add a bit more sodium if the blood test suggests it is necessary.  In extreme cases of low sodium you need to use a special re-hydration drink, or an intravenous saline solution.  Monty has a relative who keeps going to hospital for the latter.

The diuretic action of Bumetanide is a side effect of the "autism effect" and so if you can reduce the diuresis of bumetanide that would be good thing.  Researchers are trying to find a better-bumetanide and their goal is to have no diuresis.

If combining vasopressin with Bumetanide is accompanied by both reduced diuresis and a matching reduction in fluid intake, this might actually work well.  Clearly, extra care needs to be taken and what might be perfectly safe in one person may not be safe in another person.

  

Conclusion

I do have to give a big thank-you to our reader who shared his experience with Desmopressin and to the neurologist for suggesting it.

Desmopressin looks like one of those autism therapies that needs only a very short trial to determine whether it is beneficial.  This is a big advantage.

You would hope the Stanford vasopressin researchers make a short trial of Desmopressin, just to compare the effect.  They probably will not.

All you have to decide is whether it is going to be the left nostril, or the right nostril.  With intranasal insulin there was a problem with irritation inside the nose, so alternating left and right sides might be best.  You hold your breath and then squirt the spray; the objective is not to breath the spray into your lungs.  An easy mistake to make.

Note that I am referring to the 10 mcg/0.1mL Desmopressin nasal spray.  The one used to treat kids that wet their bed at night.

There is also a much more potent 1.5 mg/mL version, called Stimate in the US.  This is used to treat von Willebrand’s Disease (Type I) and hemophilia/haemophilia.  You do not want that version.  This version is 15 times more potent than the anti bed-wetting variant. 

I have been suggesting to Aspies living in the US that they give Vasopressin a trial to counter the social deficits that some find troubling.  I think they are able to obtain this via a compounding pharmacy, with a helpful doctor’s prescription.

I think outside the US your doctor will think you are mad if you ask for a specially compounded vasopressin nasal spray, or indeed a compounded  oxytocin spray.

For people unable to get the intranasal vasopressin prescribed/compounded, Desmopressin is on option to discuss with your doctor. Maybe time to develop a bed wetting problem?

The Aspies in the Netherlands have the legal option of a tiny non-hallucinogenic dose of Psilocybin once a month, which seems an effective way to target Serotonin 5-HT_2A receptor-mediated pathways and so improve social behavior. What caught my attention was that the effect of this tiny dose lasts a month and it can also be used to treat severe, otherwise untreatable, cluster headaches.

Psilocybin is the fancy name for magic mushrooms.

Psilocybin is also legal in Brazil and not surprisingly in Jamaica.  It looks like the US is moving in the same direction - medicinal magic mushrooms!

FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder

The “medical” dose of Psilocybin is a tiny fraction of the “recreational” dose and is only taken when the effect of previous dose fades to zero.  It is not a crazy idea at all, just not currently a legal therapy in most countries.  More than half a century ago Lovaas was researching something very similar at UCLA, but using LSD.

All told, there are several potential ways to fine-tune social behavior in autism. Sulforaphane is yet another option.