This blog is seen by many as being bumetanide-inspired, so it is only fair to highlight the recently published Bumetanide for autism Phase IIb results. This study probably will not get the attention it should get in the media, in part because it is French and not American.
Nonetheless, there are some interesting things in the study, most importantly is that you can see the guiding hand of the drug approving agency (the European Medicines Agency). They have specified how to measure the results (the CARS rating scale), the level of severity of autism to test the drug on (severe) and the age group (2-18 years old).
In this blog we know that autism is very heterogeneous and that while bumetanide can be highly effective, there is a large group that do not respond. This trial did not use any kind of biomarker and so it contains a broad mix of responders and non-responders.
The good news is that even though only about 30-50% of people with an autism diagnosis seem to be responders, this was more than enough to make the drug look effective in a trial of just 88 people.
The small sample size does throw up anomalies, like giving the impression that 0.5mg twice a day is more effective than 1mg twice a day, on some measures.
The most effective treatment, judged by the authors, was 2mg twice a day, but it was ruled out for the Phase III trial because of side effects.
“Clearly this trial must be viewed as a source of data on the safety and dose-ranging usage of bumetanide and it provides further support to justify a large multisite European Phase III trial.
We report here the results of a multicenter phase II dose-ranging study conducted according to a pediatric investigation plan approved by the EMA to determine the optimum bumetanide dose in ASD children and adolescents aged 2–18 years. To achieve these aims, the study population was divided into four subgroups receiving three doses of bumetanide (0.5, 1.0, 2.0 mg twice a day) or placebo. The distribution of age was the same in the four groups (2–4, 5–9, 10–13, 14–18 years old). The results of this trial confirm and extend our earlier observation that bumetanide improves the symptoms of ASD and that too in the full age range targeted.
EMA imposed the age range from 2 to 18.
CARS has been selected by the EMA in their recent (2016) guidelines for evaluation of ASD core symptoms (Guidelines on the clinical development of medicinal products for the treatment of ASD, 25 December 2015).
The mean initial CARS scores were similar across all treatment groups in the six clinical centers and were above the cut-off for severe autism as required by EMA (>34). “
In the CARS scale, a score greater than 30 is the threshold for autism. The higher the score, the more severe the autism. The regulator required that people in the trial had a CARS score greater than 34 to be eligible for the trial. The average CARS score for those in the trial was 41, so you would need an average improvement of 11 to potentially make them all “better” (this is a simplification). This just shows the meaning of improving by 8 CARS points. It is a big deal.
Here you see what happens when half a study group are not responders to bumetanide and you see a large group who either show minor improvement or get worse. This is just the expected background noise in all autism trials. There is even one person who improved greatly (>8 on the CARS scale) just by taking the placebo.
Change in the completers of the total CARS score from screening to day 90 after bumetanide (blue bars; n=52) and placebo (orange bars; n=21). All changes were calculated from the initial values for each individual participant at screening. Note a significant amelioration of the CARS scale after the treatment period (>4) is almost entirely restricted to the bumetanide-treated patients (only placebo). CARS, Childhood Autism Rating Scale.
Side effects
As we have seen in feedback on this blog the harmful side effects of bumetanide are dehydration and low levels of potassium. These side effects are entirely manageable, but that job is for the parents.
I was interested in the chart below which measures the potassium levels during the trial of the four groups. I assume green (placebo), blue (0.5mg), red (1.0) mg, black (2.0mg)
Points perhaps unbeknown to the authors
An important point we have seen on this blog is that intracellular levels of chloride vary under the influence of inflammation (which affects KCC2 expression). This results in some people responding well to bumetanide at some times and apparently not at others.
We also noted that bumetanide does not cross the blood brain barrier very well and so in some people with high levels of intracellular chloride they may appear not to respond to bumetanide, not because they do not have elevated Cl-, but because it is just too high for bumetanide to show effect.
Taken together the point is that if at any one time say 40% of people with autism are responders, there may be another x% who are potential responders to a similar but more potent therapy.
If you trial bumetanide in the summer and have a pollen allergy, it may appear not to work, as in the case of my son. Fortunately I did my trial in the winter.
New information
Dr Ben-Ari told Medscape Medical News that the phase 3 study, which is approved by the European authorities, will be performed in about 400 children in five EU countries. The patients will receive 1 year of treatment, and they will reflect the entire pediatric autism population.
"We hope to get the drug on the market in Europe for autism by the end of 2021," he said.
As some wise older person told me many years ago, "things take time". In the world of autism, things seem to take forever.
Calcium is essential for both neurotransmitter release and muscle contraction. Given these important physiological processes, it seems reasonable to assume that hypocalcemia may lead to reduced neuromuscular excitability. Counterintuitively, however, clinical observation has frequently documented hypocalcemia’s role in induction of seizures and general excitability processes such as tetany, Chvostek’s sign, and bronchospasm. The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum. Nevertheless, several studies primarily addressing other biophysical issues have provided some clues. In this review, we analyze the data of these studies and propose an integrative model to explain this hypocalcemic paradox.
ReplyDeleteKeywords: action potential, hypocalcemia, ion channel, neurophysiology, seizure, synaptic transmission
We know that Bumetanide causes potassium loss and dehydration. Less discussed is the possibility of hypocalcemia, particularly for some who show such dysfunctions even without Bumetanide.
I assume correcting hypocalcemia might make it more effective.
We are talking about a channelopathy, more precisely overexpression of NKCC1 which lets chloride into cells and underexpression of KCC2 which lets chloride out. This elevated chloride makes GABA act as excitatory rather than inhibitory. The usual balance between GABA and Glutamate neurotransmitters that controls when neurons fire is lost. The causes the so-called E/I imbalance and the visible features of autism.
ReplyDeleteHello Peter,
ReplyDeleteThis study looks quite encouraging indeed, at least for the responders. I mean a drop of beven 4 counts on the CARS score is no mean feat. I was wondering, given the observed diresct relation between dose and severity of side effects, and also, significant improvements even at 0.5 mg bid (though you frel it might be a data artefact), would a 0.5 mg dose a good place to start? I wanted to trial bumetanide once again during summer vacations. I was also thinking of supplementing with ca, mg and k and/or a good multimineral tonic instead of just potassium this time. Will that be a good idea or additional ca might be undesirable?
Regards
Calcium channel dysfunctions seem to be a part of autism so I would not add this to the mix. You could just see the effect good/bad/none from the extra calcium as a separate experiment.
DeleteThe big issue with bumetanide is loss of fluids and loss of potassium. I supplement potassium and magnesium, because that is how the supplement I use comes.
You could start at 0.5mg twice a day for a month and then increase to 1mg twice a day. Then decide if either was beneficial.
In my son 1mg once a day seemed much more effective than 0.5mg twice a day.
I am waiting to see if the genetic testing I am getting done for my son will show anything in regards to a channelopathy or something with transporters. I made a mistake on his keto-diet when I made new menus erasing casein and recalculated all of the menus-I was focusing on ratio and did not focus on the calories. My son's seizure threshold changed and it gave me the chance to re-examine. I believe GABA is excitatory...It is as though GABA doesn't function the way it should or for him its a transporter issue? Observing him in a room with other children who do not have epilepsy I can see that he is entirely too excited without the ketogenic diet. I can actually see the effect the rapid firing has...sort of like the other end has to catch up. (His teacher noticed it too when we were talking about him) The drawback to the diet at least for him is that when the ketones are too high which happens for a couple of different reasons he can get moody and sad. If he is eating every 4 hours he is ok. Sometimes you have to give a little extra carbs when you see this. Now that his ketones are back to normal though I still notice a lot of darting around but overall it is slower and depends on whether its a new environment and he doesn't want to be in it.-Infinitybeyondlove
ReplyDeleteDr Ben-Ari told Medscape Medical News that the phase 3 study, which is approved by the European authorities, will be performed in about 400 children in five EU countries. The patients will receive 1 year of treatment, and they will reflect the entire pediatric autism population.
ReplyDelete"We hope to get the drug on the market in Europe for autism by the end of 2021," he said.
Source: http://www.medscape.com/viewarticle/877562#vp_2
Peter,
DeleteThings seem to be moving. Servier and Neurochlore have signed an agreement to develop and market bumetanide for paediatric autistic population...should be available by 2021. Since the drug is already there what does that imply....they might try an d make it safer by adding potassium or what? Whatever, I hope my phase 2 trial turns out successful too. Please son, turn out to be a clear responder!
Kritika, I think they will offer a liquid version, that is easier to give to young children. The main difference is that only when it is approved will doctors in the most countries even consider to prescribe it. Early adopters who have taken matters into their own hands will see no change, except perhaps they can acquire the drug in an easier way. What about the other partially effective autism therapies? If it takes ten years to repurpose bumetanide.
DeleteHello Peter,
DeleteI feel certain observations from this phase 2 bumetanide study are important, especially for me.
1. Improvement in CARS score were greater in the 9-18 age group as compared to younger population.
2. Slow incremental increase in bunetanide dosing might reduce the risk of hypokaelimia
3. If your child gets severely hypokaelimic while on bumetanide, he is unlikely to be a very high responder. So potassium loss is not really linked to improvement in autistic symptoms. Tyler had put forth this mechanism as a probable reason for efficacy of bumetanide. Of course, one can wonder about limits and thresholds...what is the optimum potassium loss level where you see max improvement.
The data means have high standard deviations...heterogeneity and low sample size. But this sort o f explains why Monty and RGs daughter showed dramatic improvements as compared to Agneiszkas son (younger child, hypokaelemic on bumetanide).
Well, I have started my trial with 0.5 mg od and even rhat induced substantial urination. Might try 0.25 bid and take it up from there. The study recommends a lower dose for those under 25 kg but my son is almost there.
Do you think bumetanide would work for mild autism/aspergers? I have social deficits and hope this would help.
ReplyDeleteIt is worth trying, many people with Aspergers use it. Also worth trying for Aspergers, much more so than more severe autism, is baclofen which seems to help the majority of people.
DeleteI tried baclofen before and it just made me sleepy. I didn't find it to work. Not sure if it's because I took it incorrectly, wrong dose, or whether I took long enough to give a verdict. Even if it works out isn't something I would take regularly because side effects include memory and cognitive problems.
DeleteWhat dosage Do people use for baclofen?
ReplyDeleteYou would be best advised by someone with Asperger's who takes Baclofen. As I understand it, they are using a moderate dose, which would be around 10mg three times a day in adults.
DeleteThe downside of using baclofen is making you stupid and memory loss. Consider this a good trade off or not.
DeleteThe UK pediatrician using it for Asperger's has only good things to say about it. I asked about side effects and tolerance and was told they were not an issue. But all drugs have side effects in some people. I guess baclofen was not a good fit for you, but for others it seems to work well.
DeleteHello Peter,
ReplyDeleteI read somewhere that diuretics might cause thiamine deficiency. Will a good b complex or multivitamin suffice? I want to ensure to the best of my abilities that deficiencies do not crop up when I trial bumetanide this time. We had some odd neurological behaviour last time..but I am so confused about b vitamins. And then there is this whole overmethylator-undermethylator issue. How is any sane person supposed to navigate through this amazing maze. Except for B6 in combination with magnesium and to a certain degree zinc which surprisingly seems helpful for a variety of troubling conditions associated with autism ..methylation, metallothionein deficiency, pyroluria, the rest of the bs look quite unreliable. And the cherry on the cake seems histamine, the new yeast, so now there are some b vitamins and a whole range of food/supplements to steer clear off if you have histamine intolerance.
Cry-baby act aside, what would a sensible b vit combination be to go with bumetanide or you think its not really required.
Regards
Kritika, in some people it is reported that diuretics may reduce levels of folate and thiamine, but these will be much older people.
DeleteThe most important thing to supplement is potassium and perhaps some magnesium while you are about it. Many potassium supplements include magnesium. Having a daily multivitamin, with a little of everything can do nor harm and may help. Our reader Maja has found that small deficiencies in common vitamins can have behavioral effects and has explained the likely mechanisms.
This combination is inexpensive and would be a good choice to go with bumetanide.
Zinc is interesting and you do not want to be deficient in it, but it seems that in autism the problem is the Zn2+ ions are in the "wrong" place, and supplementing will not change that.
Looking across the range of ASD research and feedback that a number of ASD subtypes are due to one or more ions, potassium, calcium, zinc etc being in the "wrong" place..
DeletePeter, Em,
DeletePest ions indeed...ion species in the wrong place, in the wrong numbers at the wrong time. That is why I am wary of supplementation...did not help much in the past. Fish oils, vit A after a while made him exhibit hyperperipheral vision, finger movements near eyes. Recently my paed prescribed a combo of nicotinamide, thiamine and lactic acid and I did not like the effect. As it is, kids in urban centers, especially those belonging to middle class and above are supplemented with zinc, multivitamin, vit d, from birth. So id rather attempt to restore or maintain the levels in face of losses brought about by interventions than treat inherent deficiencies. If present at all, these are not those 'deficiencies', neurotypical ones, but 'deficiencies of the third kind'..
So does anyone from Australia manage to get a doctor to off label prescribe bumetanide or are people sourcing from the internet if so any good options. Also what changes have people noticed over what period of time. Have 4 year old son who has ok cognition numbers letters words etc. But lives entirely in his own world no social skills no life skills dressing toileting etc welcome any replies
ReplyDeleteVery few doctors anywhere are prescribing bumetanide for autism, but it is worth asking your doctor. Most people are buying it without prescription, either online from Mexico, Taiwan, an island in the Pacific etc, or in person in a country that does not strictly enforce the prescription requirement (e.g. most developing countries and Spain).
DeleteBumetanide reduces the severity of autism in responders. Autism manifests itself so differently in particular people it is best to leave it at that. If you say it helps toilet training, an adult with Asperger's will assume it is no good for him, but it might well help him.
You need to try it for a few weeks and normally within 10-20 days you will see behavioral changes. About half of people seem to be responders, some more than others.
I'm not confident that you'd be able to get bumetanide in Aus, as it's a med beyond what GPs and psychiatrist can prescribe. I feel like it's within cardiologists area and they can't prescribe stuff for autism
DeleteI just wanna share that the study is finally reaching grounds, as it's up on a renown news.
ReplyDeletehttps://spectrumnews.org/news/trials-repurposed-drug-shows-promise-autism/
Hi Peter,
ReplyDeleteI have two questions
1)What is the difference between giving diamox two times at 60 vs one time at 120 mg?
2)When is the best time to give diamox - morning or afternoon?
Thanks
-SB
SB, when you take Diamox it takes a couple of hours to reach your bloodstream, then the level gradually decreases. After 4 hours it has fallen to 50% of the peak level - this is called the half-life. To make the drug more effective it is usually taken twice a day. So 60 mg twice a day should have a better day-long effect than 120mg once. There are different modes of action for Diamox. Different dosage levels will produce different effects, as with many drugs.
DeleteI am not a regular user of Diamox, but some readers of this blog are. They would be the best ones to answer your question. My feeling would be to give it at breakfast and then in the late afternoon.
SB, I've used Diamox mainly to control severe channelopathy-related headaches in my son. It also brought improvements in autism. At one point I changed 60 mg twice a day to 120mg in one daily dose and headache returned immediately, so my conclusion was that dosing Diamox two times a day was more effective.
DeletePeter, are you aware of any known relations between Diamox dose and its different modes of action/effects?
Agnieszka, the dosage used to change the pH of blood so that it carries more oxygen is very much higher. It is 250mg twice a day. That is an effect via AE3. This was my original idea as to why Diamox might help in some autism, in addition to the fact that it should lower intracellular Cl-.
DeleteI just found a paper I had not seen on this exact subject
Carbonic Anhydrases and Brain pH in the Control of Neuronal Excitability
https://link.springer.com/chapter/10.1007/978-94-007-7359-2_14
Diamox affects sodium channels and also CIC-1, probably more.
The effective dose for Hypokalemic periodic paralyses varies widely 125-1500 mg/d in divided doses.
Peter, lowering the pH of blood is considered responsible for Diamox effects in altitude illness prevention and for this 125 mg twice is used in adults and 2.5 mg/kg of body weight in children. This is rather low dose, but recently it has been suggested that other Diamox mechanisms might be involved eg. Nrf2 activation.
DeleteDiamox was also found effective in electrical status epilepticus in slow-wave sleep (ESES), EEG phenomenon which may be associated behaviours that could be easily diagnosed as „autism” without prolonged sleep EEG done. 10-20 mg/kg was used in children with ESES:
https://www.ncbi.nlm.nih.gov/pubmed/26230617
Actually I am not sure what I am currently targeting while using acetazolamide?
Unfortunately I can't access the full text of the book chapter on carbonic anhydrases and it has some interesting keywords including KCC2.
My child has autism "flare-ups" like you describe, when she is more prone to behavior outbursts and some of her effective therapies appear to stop working. We are not sure if these are related to allergies or some other inflammatory process (she has in fact lost many teeth in the past months). You have made many helpful recommendations for managing behavior flare-ups, but I want to make sure my toolkit is current. We are trialing: sytrinol and quercetin daily (we saw no improvement with L. Reuteri) and claritin and/or ibuprofen as needed to manage acute problems. Is this consistent with your most current recommendations? Thank you.
ReplyDeleteLosing milk teeth and the eruption of permanent teeth releases pro-inflammatory cytokines that very likely makes your daughter's autism worse. This goes on for many months.
ReplyDeleteIbuprofen in particular should help, sytrinol and quercetin are also a good choice.
If her problem is allergy-related and Claritin is not sufficient you might need something stronger. In the summer I use azelastine nasal spray and verapamil. This year I will add L-histidine, which in theory should help and is OTC.
If your daughter's problem is linked to Th1, Th2 and Th17 most interventions are drugs.
Since they are flare-ups rather than permanent, it is worthwhile continuing to look for the trigger. So if it was allergy, when you go to the seaside or the mountains, there should be a change.
So, we'll have to wait for around year 2021 before Bumetadine is available as an official medicine for autism (if phase III succeeds that is) And then we will have to wait for another couple of years before we have a better variant with less diuretic effect. Or?:
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/24615913
Btw, does anyone know which european countries that will participate in the phase III trial?
/Ling
If it takes 10 years to approve bumetanide, it will likely take 10 more to approve BUM5, or whatever they come up with. Ben-Ari did mention a bumetanide analogue to me a while back; it all depends if they have the money. Clearly the analogues are much more potent. This is why it makes sense to add further therapies that lower cl-, in those who respond to bumetanide.
DeleteOne reader in Spain said there would be a trial there.
I was told that France, England and the Netherlands were chosen for phase 3, but it was long ago. Being a great admirer of the French research, when I recap my son’s last two years on bumetanide I can see only one risk of getting into the clinical trial: ending up in a placebo group.
DeleteThanks to Peter’s idea my son has been also on KBr for over a month with social and cognitive effects at least comparable to bumetanide. In particular it’s about peer interactions and skills that he was thought previously not able acquire eg. reading.
Peter, do you think that KBr as monotherapy might be an alternative for these children who seem to benefit from bumetanide, but have issues with potassium control (eg. no easy access to lab tests) or finding urination stressful?
It seems to me that some common side effects of bumetanide, while not dangerous, may easily spoil the potential for improvement. My son would be the first to drop out from the trials with his hypokalemia and if not for severity of his ‘autism’ perhaps I would not insist on finding a way to teach him drink more fluid with 2 x 1 mg dose etc. So, can I assume that the response rate for prodrug without renal effects could be higher than what was found for bumetanide?
I understand that no-one is interested in trial of verapamil for which I pay 2 euro per month, but what about bumetanide prodrug for 1:68? How can this be accelerated?
The advantage of bumetanide is that it is cheap and widely available. People in the US will only be able to access KBr made for pets. If your child has type 1 diabetes you have no choice but to adapt to it, otherwise you will have one less child. I think people have to adapt and learn how to deal with bumetanide. I would sent parents on a half day course to learn about low potassium and signs of dehydration.
DeleteWe cannot influence how many years it takes to approve a more potent version of bumetanide. Eventually Ben-Ari will do one version and a company in the US is developing its own version, no targeted specifically at autism.
I think some parents will be bothered by bromo-acne, so I think the uptake of KBr will be similar to verapamil. The information is now out there and people can choose to find ways to try it, if they want.
Don't you think all participants will be in the placebo group for a while? 3 months with drug and 3 months on placebo or vice versa. I can see another disadvantage if participants are not allowed to have ABA during the trial period...
ReplyDeleteHow much potassium are you adding per day and kg? ( I understand this is highly individual, though.)
At the moment it seems impossible for me to get Bumetanide from an (at least) halfreliable source in europe. Maybe I'll start with Nac/fluimucil instead since that whas easier to find, even as a syrup for kids from age 2. Having an EEG upcoming, what washout period would be advisable to get the most reliable resultat from that?
/Ling
Ling, I give 7.5mg/kg of potassium twice a day at the same time as bumetanide.
DeleteIn Europe you will likely have to buy on-line, or go to Spain in person and ask the pharmacist nicely. It will be a few years before you can get it locally. It is a very cheap drug, not the sort of thing people are likely to fake.
You could contact http://www.neurochlore.fr/ and ask to join their trials.
I would stop the NAC a few days before, if you want not to have its effect.
Hi again,
DeleteSeems even the non-reliable sources of Bumetanide I've found on the web won't deliver to my home country. I've probably spent 40 hours trying to find a way to buy it...
I am now trying to convince the rest of the family to go to Spain ("Wouldn't it be a nice holiday?"), though I have no idea on how to convince any spanish pharmacist to give me pills without a prescription. I do feel stupid and fraudulent, but I keep reminding myself of why I am doing this.
So, any advices and ideas on where to go in Spain and what to ask for and say would be helpful. Maybe there is some spanish readers of this blog who could give me a hint?
Plan C is to find a private doctor anywhere else in Europe who would prescribe it for my daughter.
Thanks everyone!
/Ling
Hi Ling,
DeleteAn option is to go to a private, anti aging specialist on Harley street. They are expensive, but willing to do more tests, and if presented with all the trials and papers, more willing to prescribe.
Ling, did you try to ask your daughter’s GP or neuro about bumetanide rx? It depends on a country, but I know some parents who got this drug from a ‘mainstream doc’ providing papers on bumetanide clinical trials, especially the French RCTs and safety data. Where do you live?
DeleteThere is also example of n=1 off-label bumetanide use at the academic center in the Netherlands:
https://www.ncbi.nlm.nih.gov/pubmed/26216321
In my opinion it is also a good idea to ask for something similar at the local medical university.
Anyway, do you have an opportunity to measure potassium blood level when you obtain bumetanide for your daughter? Can you do it on your own or can your GP help you with monitoring potassium and best also with fluid balance on bumetanide? Sorry for so many questions, just thinking how you can get it.
Hi Ling, have you tried searching for 'miccil' instead, it is a Spanish/Mexican name for bumetanide.
DeleteA brand of Miccil is labelled as Burinex and Fordiuran made by Leo Pharma. Goldpharma.com is usually reliable.
Thanks all, you are very kind trying to help me!
DeleteI've probably searched for all names available on Bumetanide, from Mexico to New Zealand.
I haven't talked to my GP, but the general answer from the most respected autism centre here is that prescription will be possible when the phase III study is finished in France. But you are right, maybe I could collect all data I have and at least make a try.
I live in Scandinavia, not wanting to be more specific since giving a child prescription medicines without prescription is illegal here (for obvious reasons). It is also illegal to not give your child medicines that he or she needs...
We had a baseline potassium level measured lately, but I haven't figured out how to get another blood sample done yet. Seems the private blood test companies only do adult people here. This will be my next challenge.
Autism is a marathon, right?
/Ling
Ling, in this marathon I found some of the respected 'autism experts' in my country the least helpful. Other professionals e.g. immunologists at least don't need to overcome misconceptions and own beliefs, maybe that's why it gets easier. I think that bumetanide is an evidence-based intervention in autism. You can email me if it would be easier to discuss this without concerns about being anonymous.
DeleteAfter a phone call with the doctor I feel some hope that we can convince her on trying bumetanide. She is a pediatric neurologist at one of my countries biggest hospital for children and she had not heard about bumetanid before.
DeleteI have gathered all relevant papers, cases and other documentation on the subject and will send it to her for reference. My hope is not only to get a prescription for our daughter, but also pave the way for other ASD/epilepsy/DS children here. Wish me luck!
We will have to wait until the end of the summer though; these pediatric neurologists have a month-long queue for appointments. Maybe I should come up with something else to try meanwhile.
/Ling
Ling, good luck with the neurologist. This would be a good solution because then your GP will likely be willing to help with checking potassium. If you have not tried NAC yet, this might be a good time. The easy to take form is the effervescent tablet (fluimucil/Sandoz ACC/pharnaNAC).
DeletePeter, whatever you think you ARE changing the autism world.
DeleteThanks to you, the head neurologist at my countries main pediatric hospital is now well educated regarding Bumetanide for autism. I also know that there where some discussions with colleagues at this and other hospitals, so the word is spreading. The first patient is already signed for a trial later this year... :-)
/Ling
Ling, that is great. There are indeed small steps in right direction and over time this can result in significant change, but I suspect for many years it will be up to parents to push for autism therapies, rather than just sit back and receive them.
DeleteIn countries with socialized healthcare, like Sweden and the UK, patients do not expect to have to "shop around" for treatment, it is not something people do. In this respect the US, with its highly inequitable healthcare system, makes parents much more demanding of their doctor.
Hi Peter, my boy (almost 17) weighs 120 kg. I've started him on K-bicarbonate, and it seems to be helping (along with Bumetanide 2 mg once a day). I have no idea of how much potassium I could give to him (since bumetanide is depleting K). If I go for the same amount of you, it would be about 900 mg, twice a day. Is it correct ?
ReplyDeleteLuis, I would give bumetanide 2mg twice a day. Giving large amounts of potassium supplement is not safe. You can give potassium in food without risk. So give bananas, kiwi etc. You can give 500mg potassium tablets, but it is better to give one three times a day. 1000mg of potassium may cause a problem, even though your son is big.
DeleteOK, Peter. Thank you for your reply ! Best of luck !
DeleteThis comment has been removed by the author.
ReplyDeleteI'm an adult male wit Aspergers Syndrome. I weigh 165 pounds. What would be a good Bumetanide dose for me? 1mg twice a day or 2mg twice a day? How many hours apart are the doses given?
ReplyDeleteI would try 2mg twice a day for a month and look for an effect developing after a couple of weeks. It causes diuresis and so when you give it depends on your schedule. My son takes it at 7am and 5pm. You have to replace the lost fluids and potassium otherwise there will be side effects (dehydration, drop in blood pressure and low potassium). Ideally you check blood potassium level and maintain at the upper part of normal. The effect takes time because it very slowly reduces chloride levels.
DeleteHow long did it take to notice a difference for your son? What did it improve? Executive functioning? Irritability? Social deficits?
DeleteThank You.
Dez, it took 10 days and the improvement was executive functioning and mood. Many people with Asperger's also benefit, but they will likely have a slightly different experience.
DeleteUnfortunately I couldn't tolerate the hypokalemia caused by Bumetanide 2mg twice a day. I was on that dose for 3 days. I have been on 1mg twice a day for the past five days and I have not experienced any side effects. I have been drinking 2 cups of coconut water per day (940 milligrams total) and eating one banana per day(470 mg total). Realistically how much more potassium should I consume if I go back up to the 2mg twice a day dose?
DeleteDez, it varies greatly from person to person. It is best to measure the level of potassium in your blood. You cannot do any damage by eating bananas, so you could eat 2 or 3 a day. You could try a 500mg supplement with a large glass of water each time you take bumetanide, and then add dietary potassium on top of that. My son has 2 bananas and about 1,200 mg of supplement, but some people take much more. About 30 % of people lose a lot of potassium, but 70% have just a minor issue.
DeleteThe problem with potassium supplements is that they only deliver 90-99 mg of elemental potassium per pill. I guess I should just target the maximum RDA for potassium through food sources.
DeleteDez, it depends where you live. In the US by law they cannot put in more than 99mg. My cheap French effervescent tablet has 500mg of elemental potassium, and I give up to two tablets a day. Make sure you drink enough fluids, you may need 3 litres. I would look for some cheap small 99mg pills.
DeleteHi,
DeleteCan you tell me the name of the French tablet? Maybe I can get it online. Taking too much of the small 99 mg pills can cause GI problems.
Thank You.
Dez, the brand is Biofar. I think if you crush five 99mg pills and dissolve in a large glass of water you will end up with something very similar. Or crush and take with food.
DeleteIf you plan to crush the pills anyway, then maybe better buy just powder? For example Potassium Gluconate Pure Powder (I believe Tyler said he preferes gluconate form, but clearly people see bumetanide benefits on different forms - including potassium chloride)
DeleteThe powder is a very good idea, I am surprised it is legal in the US. They seem to want to stop you getting access to potassium.
DeleteHi Peter, how long do you think that I could start supplementing GABA after having started Bumetanide ? Thank you.
ReplyDeleteGABA itself is supposed to not cross the blood brain barrier, so in theory GABA should have no effect.
DeleteSome people do use Picamilon is a drug formed by a synthetic combination of niacin and GABA. This does cross the blood brain barrier. It is sold as a supplement in some countries.
I am not convinced either will help. I tried one tablet of Picamilon and it made things worse very quickly.
So, Peter, why are you using Bumetanide, if not to supplying GABA ? Maybe you think that the GABA already existing in the brain would be enough, since the chlorine is out ? (Sorry if it's a dumb question.)
ReplyDeleteLuis, it gets complicated. Bumetanide is changing the effect of GABA, because in much autism it is not working as it should, so it is not inhibitory. By moving chloride from inside brain cells to outside them, GABA should become inhibitory. Having begun to work correctly, you might think that extra GABA might help.
DeleteIt seems that while bumetanide does help, it does not lower chloride far enough, so additional interventions can further improve things, by further lowering chloride.
Peter, and these additional interventions to lowering chloride further would be ... ? Thank you for your help.
DeleteLuis, this is all experimental.
ReplyDeleteI use potassium bromide to further lower chloride, some people use Diamox (acetazolamide) which has several effects, one of which may be to reduce chloride (via something called AE3).
GABA can also be made more inhibitory by upregulating the alpha 3 sub-unit, using tiny doses of clonazepam, about 0.025mg a day. This is based on some quite serious research, albeit in mice.
Thank you very much, Peter. Maybe it would be of general interest telling you that my son is having high pressure spikes after 2 days of upping his Bumetanide dose to 2 mg. I assume that this could be due to potassium depletion, even giving him 1,500 mg/day, in 99 mg capsules spread through the day. I am stopping Bumetanide today (planning to resume it a few days ahead). Maybe Diamox could be a better option now. I am very thankful to you.
ReplyDeleteYou may be giving too much potassium. It is best to check his blood potassium level. If you use food like bananas and kiwi, you can raise potassium levels very safely. Also you need to drink a lot of water to replace the lost fluid, I think this is why some people have side effects, they underestimate how much fluid is lost in diuresis.
DeleteI have never given 1,500mg of potassium per day in supplements. It is better to give two bananas.
Hi Peter and Luis,
DeleteI have recently increased bumetanide dose to 3 mg daily for my 9 yo son and started KBr. He's also on Diamox.
My son is prone to potassium loss. He wouldn't be able to use bumetanide without dietary potassium together with supplementing at least 1500 mg K per day (often even more). As it is very unusual to give two diuretics and so much potassium to a child I asked the French researchers, consulted pediatric cardiologist and nephrologist and in case of my son neither was concerned - provided normal kidney function and after some blood tests done, ECG, kidney ultrasound etc.
Of course it's just n=1 example and It might be different in other children. What I am trying to say is that with careful monitoring some unusual solutions with bumetanide and potassium are safe and may work well.
All in all targeting chloride neuronal regulation is the most effective intervention in my son with regard to many aspects of life.
I did most tests on my own, but a friend of mine who obtained bumetanide elsewhere asked her child's GP for help with electrolyte monitoring and the doctor was helpful. Perhaps it depends on where you live. Electrolyte panel is a simple and cheap blood test which would be the first thing I would do when using bumetanide with unexplained issues.
Hi Agnieszka,
DeleteI resumed giving Bumetanide to my son, 1 mg twice a day. He's doing fine with this, but I have to give him large amounts of Potassium Bicarbonate, spread along the day. I like this form of Potassium because it does not cause acidity.
Hi Agnieszka, thanks for your feedback on Bumetanide use.
DeleteI give 1mg Bumetanide together with 15mg Fluoxetine in the morning and wonder if there is be a drug to drug interaction.
I know Fluoxetine is a potent Cyp2d6 inhibitor but I don't know the enzymes involved in Bumetanide metabolism.
I would very much appreciate your comments in case you see interaction.
Hi Petra,
DeleteIt seems that more than 2/3 of bumetanide dose is not metabolized at all - so no risk of CYP2D6 influence here. It is not clear what about the rest. So in theory, with regard to possible interaction due to CYP2D6 inhibition, the risk cannot be high.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435036/
I always check interactions here:
http://reference.medscape.com/drug-interactionchecker?cid=med
And it says:
bumetanide + fluoxetine
Minor
Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Possible additive hyponatremia.
If they say "minor" in the U.S. then I think it is really not risky.
Have you tried to increase the bumetanide dose for your son? I saw the best of bumetanide only with at least 2x1mg.
Hi Agnieszka,
DeleteThank you for your kind reply.
I noticed that there is a minor interaction between the drugs, due to possible hyponatremia, but still needed your reliable view.
My son's sodium level is 145mmol/l and seems fine.
His potassium level is 3,85mml/l (no extra supplementation/bananas, just big fresh orange juice) which also seems good, checked it twice, and I may add 1mg Bumetanide more in the near future.
It's really nice that your son responds well to 2mg and hope the best for him.
Hi Petra,
DeleteI was thinking about your son’s sodium and potassium results. And my son’s as well – he has similar. Na+ level of 145 mmol/l would be regarded as borderline hypernatremia by some labs. It might be related to loop diuretic (eg. bumetanide) induced dehydration. My son’s Na+ was 144 mmol/l and despite no obvious dehydration signs his mood got better with additional water to drink. I haven’t yet measured his sodium level after this to be sure about this idea though.
Also K+ level of 3,85 mmol/l is within normal range, but I saw that for my son K+ over 4 mmol/l is best in terms of more stable behavior. Perhaps it might be sensory related. I never managed to increase his K+ level further, but this seems to be beneficial for some children with autism. I’ve also read the opinion of an adult with Asperger’s who claimed that some people with the same diagnosis feel better with potassium level reaching upper normal range. Unfortunately I can’t find the source now. Did you try to supplement potassium in your son?
Hi Agnieszka,
DeleteI saw your comment but have been busy to reply because my 17 year old niece, from my husband's sister, has had a second psychotic episode and she is in clinic. This made me completely disorganised and sad.
I think 1 mg Bumetanide can decrease potassium in my son by 0,5. Supplementing 400-500mg at a time is safe. Maybe more than that doesn't bring behavioural benefit, unless there is an emergency and suspect hypokalemia. What I am saying is more or less what Peter says about it.
As for the borderline hypernatremia you mention, I would agree that it might be related to Bumetanide. There are some indications that my son may be marginally dehydrated and also checked his sodium before the diuretic and was lower (139mmol/l).
For the time being I am trying to deal with vitamin D deficiency (7.0 ng/ml). The rheumatologist says he needs 4.000IU a day for six months but the angiologist says not to worry as at such time of year almost everyone may be found deficient and it's going to be fixed on its own, by sun exposure.
On the one hand there are research papers claiming significant improvement through supplementing D3, but on the other hand there is this calcium malabsorption and the formation of steroid hormones which make me anxious to use.
Until I decide what to do I give fish oil (not cod liver oil) which seems well tolerated and sun exposure whenever possible.
Have you checked vitamin D for your son?
I read that it can also improve speech, maybe through serotonin which helps with brain connectivity.
Hi RG,
DeleteI missed your comment and place my reply here in case you want to see what I wrote to Agnieszka.
You say 5htp may help with anxiety causing speech problems and I should add here that it may be due to brain connectivity affected by serotonin, but anyway we are probably talking about the same thing in other words.
I would have kept 5htp if it rescued OCD and sensory overload but it didn't and had to try Fluoxetine for that. It's a different mechanism and short term use shows that it can help.
There is research on autistic/asperger's adults treated with Fluoxetine with good results.
I would also like to describe an incident happened during a day without Bumetanide (had to avoid diuresis) using only Fluoxetine. By afternoon I saw a "frozen look" which I am sure could have led to severe trouble and gave Bumetanide at once. It seemed like I had pressed the rest button.
What I am trying to say is that if someone's GABA keeps excitatory, modulating serotonin itself doesn't work. I have similar examples while trying to fix dopamine.
RG, how are you going to use nicotine for your daughter?
And one more question, is your daughter ok with vitamin D3?
Petra,
DeleteI am sorry to hear about your niece, it is indeed very sad.
What I meant was that with blood tests and monitoring symptoms you can probably fine tune electrolyte balance and hydration while on bumetanide to get the best effects from the treatment.
Unfortunately I cannot say anything conclusive about vit D. My son was deficient and improved over the time without supplementation. I tried some high dose vit D anyway few months ago according to promising research results that you mentioned. The effect was quite a disaster as it made my son extremely hyperactive, toe-walking (something not seen for years), agitated and very distressed. This was reversible and I tried twice as I was not sure if it's vit D related. When I saw him toe-walking once again I immediately stopped. Actually I don't have a clear explanation for this (calcium issues?).
Regarding Vitamin D, an interesting combination that I believe has been covered here in the past is Vitamin D3 and K2 combo, which Thorne provide in a handy bottle with hundreds of servings (two drops each).
DeleteCuriously there are some light sensitive enzymes that can exacerbate ASD symptoms in bright sunlight too..
When u say 'u are tying up loose ends with your blog' does that translate into u are winding down to end your blogging?
ReplyDeleteI hope not!
Dez,
ReplyDeleteCan you please tell me what symptoms do you feel from hypokalemia ? My son is autistic, non verbal, and I would like to know how does he feel. Thank you !!
Fatigue, Weakness, Muscle cramps, and palpitations.
Delete3 g of Potassium Bicarbonate is equivalent of 1.17 g of Potassium. I am using Potassium Bicarbonate because it is alkaline, and my son has stomach issues. I don't know if it has a good absorption, but it has not caused any stomach pain.
ReplyDeleteI am not sure where to post this...
ReplyDeleteI have been following your blog for a couple of years now and am super impressed at your constant search for more knowledge and help for your/our children.
My son, 12 years, is high functioning ASD.
We live in canada and not sure how many followers here do as well. And I am unsure how many of the drugs u post about are available here in the boondocks.
But I wanted to also state that I have tried so many different alternative modes of therapies and interventions over the past 10 years and he is still the same 'high functioning' child as he was. I did try homeopathy and went to a DAN doctor as well. I have since stopped everything and all he is on is 1 mg of Intuniv daily for impulsivity.
When reading your blog I feel that I am neglecting him. I should be giving him SOMETHING for g-ds sake I shout to myself. My point is.....where do i start? It is all very overwhelming. He talks to himself almost all the time and makes 'crazy noise' a lot.
My question is: Is it too late to start? And if the answer is no - where does one start to know what to give my son?
Debbie, it is never too late, but if he is high functioning and has no really big issues I would not get carried away.
DeleteI would start with an antioxidant like NAC and see if it helps with his talking to himself. If he swallows pills, NAC Sustain 3 or 4 times a day is a good start. If it is going to help, you will see an effect in 2 or 3 days.
Bumetanide and Baclofen are worth trying, but these are prescription drugs. People buy them on-line from places like Mexico. Baclofen seems to work for many people with Asperger's. Bumetanide works in about 40% of cases and they can be anywhere on the spectrum, so it is a case of trying it for 2-4 weeks and see if it has an effect.
Thanks I will start with the NAC
ReplyDeleteWhen u ask if he has any real issues, I mean he IS on the spectrum. So he's completely anti social and could not care less if he interacts with anyone. I find it so hard to find a way to motivate him as nothing or nobody really makes a bit of difference to him. As long as his schedule is pretty much unchanged, he's ok.
Am I supposed to think I can 'fix' him? When do we know that this is as good as it gets?
Debbie, strange as it might sound, the milder the autism the bigger some problems become. The lack of social interest is a big part of Asperger's, some people want to change themselves to fit better into the world, but others are very happy as they are. There are forums where adults with Asperger's compare notes on what helps.
DeleteIn many people with autism oxytocin from L.reuteri probiotics makes them more emotional. One is Canadian, Bioamicus and the other is Biogaia Protectis. The effect is within a day or two.
You might find bumetanide and/or baclofen helps.
Adults with Asperger's do seem to experiment with things that affect serotonin.
You could easily try 5-HTP, which many readers of this blog seem to find effective. People use about 1mg/kg split into two doses.
It does seem that the majority of people with autism do benefit from pharmacological intervention. You just have the find the right one(s).
Debbie, as you may have seen in my blog, autism, schizophrenia and bipolar are all overlapping spectrums.
DeleteWhat you describe sounds more like the negative symptoms of schizophrenia - which include apathy, social withdrawal, and a lack of emotional expressiveness.
My son, also with an autism diagnosis, does not have those attributes.
This might suggest that you look at therapies for the negative symptoms of schizophrenia, some of which overlap with autism therapies.
An example:
http://jamanetwork.com/journals/jamapsychiatry/fullarticle/1660588
Conclusions: Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms.
While bumetanide reasonable available from online sources anyone have access to potassium bromide finding rather hard to even find online and would be interested in trying this out cheers
ReplyDeleteAs a drug for humans you will only find potassium bromide in Germanic countries or nearby. As a powder it is used for non-medical purposes. It is used by vets to treat cats and dogs.
DeleteThank you so much Agnieszka, I thought so, that's why I feel reluctant to give. I've seen my son toe walking many times together with stretching his upper sides of spinal cord.
ReplyDeletePeter, I have been thinking about inosine today. It is the endogenous ligand that binds to benzodiazepine site of Gaba and a precursor of uric acid, both of which problematic in my case report.
ReplyDeleteI just made a simple thought to connect Gaba with purinergic function and don't know if it stands.
However, guess what, my son's serum uric acid is absolutely normal (5.3), dropped two points all of a sudden, to my complete astonishment and urate remained stable in the upper normal means.
I also need some clarifications about Gaba inhibition.
There are two different types of Gaba inhibition, fast and tonic, mediated by synaptic and extrasynaptic Gaba respectively. The synaptic sits in the membrane of its neurons at a synapse and the extrasynaptic sits at the spinal cord.
I suppose Bumetanide acts upon synaptic/fast inhibition, but does it affect some isoforms found extrasynaptically, in spinal cord for example?
I am really sorry if I oversimplify things here.
Been hearing a lot of talk but have there at least been one reader on this blog with success on bumetanide?
ReplyDeleteWe are actually just starting back on Bumetanide, 1 mg separated into 2 doses, to regulate GABA/Glutamate. My son has SPD and with seasonal allergies comes a lot more hyperexcitability, which he already struggles with year round. He stims and has almost spastic behavior with his limbs. Lately the muscles in his feet have been so tense, the big toes curled over almost permanently, causing the skin to crack underneath. Bumetanide regulates the G/G cycle better than anything else we've tried. Muscle tension throughout his body is drastically reduced and the stimming is lessened though never completely gone. Previously, when we first tried it at age 2, I noticed it also regulated his sleep cycle.
DeleteMKate
MKate, re: your son's muscle tensing, have you tried supplementing extra thiamine? in the co-enzyme form? Thiamine may become depleted using loop diuretics - although I know Peter has mentioned that happening with bumetanide is rare.. However, it's "autism" so........There of course are alrady opinions out there re: low thiamine and autism anyway.. wanted to mention just in case. Best wishes!
DeleteIn my son bumetanide reversed cognitive decline that occured with his late regression, reduced much sensory suffering, did not improve expressive speech, but increased communication skills to the point he could tell us about his severe migraine headache misdiagnosed earlier as mood disorder. Now he's been recently found to be in average range on non-verbal IQ test, while three years ago he scored 40 points less (moderate intellectual disability), at least some of this can be attributed to bumetanide treatment as before there was no improvement on various developmental tests and in life. Together with acetazolamide and mast cell targeted treatment his slowed and epileptiform EEG improved to borderline normal. Cognitive gains, more awareness which in turn brought social improvements and relations, sensory relief are the main benefits. Less medically speaking he gained some meaningful life, although still is affected very much. More than two years on bumetanide at the moment.
ReplyDeleteIn a few days on Bumetanide we are seeing gains: more calm, better sleep, more speech. The only problem, until now, has been to control potassium depletion, with supplementation.
ReplyDeleteTry Spironolactone
DeleteThank you, Em ! It's on my thoughts, but it has some side effects, too.
DeleteDid you try it together with bumetanide? If so, what doses of both? How did the potassium level change and how often did you monitor it?
DeleteAgnieszka, I have tried Spiro 25 mg a day, along with Bumetanide 1 mg, twice a day. My son usually has stomach pain, and I stopped Spiro because of that (it can interfere with ulcers healing, although I can't say my boy has ulcer). I won't be of help to you regarding potassium level monitoring. My boy has grown up too much, is extremely strong, and won't allow us to collect his blood. We try to control it by symptoms (legs and arms muscles very rigid, shortness of breath, sleep problems). Today, I gave him 5 drops of Potassium Phosphate (ionic, from BodyBio), and it seemed to have done good for him. (Sorry for my poor English.)
DeleteThank you Luis. Actually it seems like high potassium dose is not a problem in people on loop diuretics with normal kidney function. My son did not tolerate many potassium supplements because of stomach pain. He can use only liquid/effervescent ones. Now it is Sando-K from the U.K.
DeleteAgnieszka, my son also has a very sensitive stomach and duodenum. I'm giving Potassium Bicarbonate, that is not acidic (on the contrary, it is alkaline). But the absorption is not so good. Yesterday and today I've tried Potassium Phosphate (ionic liquid drops), with much better absorption (based on symptoms), but it also gave him stomach pain.
DeleteLuis, did you try mixing the supplement with food? That may avoid the stomach irritation.
DeleteYes, Peter. I'm giving it with food. But, even so,...
DeleteAgnieszka, have you noticed that Sando-K has chloride in it ?
DeleteWell I have never seen any bad reaction to Sando-K.
DeleteBut as in my son every step taken to regulate chloride neuronal concentration really brings improvements as was suggested by Peter, your comment makes me wonder if chloride intake and blood level also matters.
In the French trials they used liquid potassium gluconate which is awful. Somehow they managed to give it to children though.
Peter, what form of potassium do you use? I can't find the Biofarm supplement ingredient list online. Do you think that chloride should be avoided either in food or supplements?
Agnieszka, the Biofar product contains potassium citrate and potassium bicarbonate.
DeleteI did wonder about food with salt (NaCl) and other sources of chloride. It should be the chloride gradient that matters, rather than the absolute level inside and outside the cell.
It may make no difference, but I personally would avoid extra chloride, just in case.
It might even be that dietary chloride is good, because perhaps it will reduce the difference between intracellular and extracellular chloride.
Since sodium is generally not good for you and most people have too much. I look to add potassium in diet and avoid salt.
Thanks. I will try to find potassium without chloride.
DeleteThere is rx citrate/bicarbonate product in Poland, but for the reason I cannot understand it has a pink food dye added, which is suggested to induce mast cell degranulation and indeed it does it.
When going on the goldfarm.com site, they still require a prescription, do they not? What does one do?
ReplyDeleteMy 5 yo son has P and N type calcium channel binding antibodies. Per the Mayo lab testing they say it is indicative of a possible autoimmune encephalitis. I received an email from his neuro today that he wants to trial Butemanide with him. We have done several rounds of ivig with limited success. I saw you said that calcium channel problems are common with autism- but I can't find much about this. Any thoughts?
ReplyDeleteYou need to consult an expert regarding Voltage gated calcium channel (VGCC)-antibody-positivity, to rule out serious problems.
DeleteVoltage gated calcium channel antibody-related neurological diseases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360501/
Bumetanide is a very good idea to try and you have a 40+% chance of you your son responding well.
Calcium channel problems are a core feature of autism, but they are not all the same.
I would make the trial with bumetanide and rule out any wider issue with the VGCC antibodies.
We are followed by a prominent neuro in the autism world. He doesn't feel there are any paraneopastic syndromes occurring. We are going to start at .5 mg/day for a week then increase to twice a day.
DeleteIt signed me in this time and made me anonymous last time. I'm the same poster from above!
DeleteDear Peter and others!
ReplyDeleteI want to check the kalium values in the blood of my child: via internet you can order a kit for a finger prik. The analyse wil be run by a lab. Do you think this is reliable enough with capillary blood?
Thank you very much!
I looked it up and labs want you to take sample from a vein.
DeleteAlso potassium leaks out of red cells and results obtained by post are consequently unreliable. For this reason the sample needs to be centrifuged as soon as it is taken.
Having said that I did check potassium in my son once with the nurse taking blood from his finger.
In many countries you can do blood tests without going to your regular doctor, but it may not be cheap.
It all depends where you live, but even in the UK you can now get your own blood tests. Just look on google.
In some countries blood testing is a walk-in service. You pay, they take the blood and email you the results.
Exciting news for a very small fraction of the readers:
ReplyDeleteGillberg centre in Sweden will have an independent Bumetanide trial later this year.
Seems they finally got the funding.
/Ling
Oh, that's interesting news. Live in Sweden. Where did you get this info?
DeleteAnonymous, try to get in contact with Elisabeth Fernell at GC.
Delete/Ling
To be honest I did a lot of research on bumetanide and I can't find many success stories. I have Autism which mainly affects my ability to connect with people. I will be trying this medication for a month at 1mg, 2x a day. I will post if I see any results.
ReplyDeleteI was Informes of this drug by a friend. I had been looking into Suramin by dr.Naviux which had amazing results. Have you looked into it peter? In the small trial they had with it, the children were speaking, making eye contact and had a 100% success rate. Even putting them out of the autistic scale. What do you think of it peter?
Suramin is interesting, but outside a handful of African countries you cannot obtain it.
DeleteThere are many drugs and supplements that can improve Asperger's, but it is rather a case of trial and error.
Hi Daniel,
DeleteReading up on the wiki page for suramin it has some nasty side effects, now even though these do these would obviously not effect anyone it does seem like a bit of a risky drug.
Not to mention it can also only be administered by injection, that being said it does have an insane long half-life which can be good if its working properly.
Daniel what is your exact diagnose, the word autism is such a broad term these days, I suspect as Peter says you have Aspergers like myself?
When going on the bumetanide please update once a while to let us know how it goes, this would greatly help others aswell.
Oh nearly forgot to ask Daniel, if you do indeed have Aspergers syndrome like myself, do you feel you are way more thirsty than 'normal' people aswell?
DeletePeter,
ReplyDeleteI've been following your blog for over 3 years now (after stumbling upon it while researching sulforaphane). My 11 year old son has "mild" behavioral autistic symptoms but I consider him to be a moderate case overall because his IQ is only in the mid-50s and he struggles to learn anything (in part because he's incredibly inattentive and wild). So far, nothing has really helped much. Per your site, I tried biotin (no effect), NAC+ chocolate flavanoids(sp?) (but he hated the taste). We also tried Sensory Therapy which might have helped a little.
I've decided to do a trial of photobiomodulation, using the Vielight intranasal 810, for a few months (see links below). If it doesn't help, then I will ask(beg) his doctor for a trial of bumetanide- or make another attempt to get it on my own.
There are numerous photobiomodulation papers on pubmed but very little info on it's possible application with autism. There are some small but compelling studies that suggest it's effective with Alzheimers and TBI (tramautic brain injury). The only person I found who's tried it for autism is the 2nd link below- but her dosage (seconds only) seems too low for me. Another cheaper alternative is Red Man Light, which is a UK company. Best regards and Happy new Year.
Ryan's Dad
https://vielight.com/references/
http://expresslyelizabeth.com/lllt/
We have encountered possible bumetanide issues now approx. 6 weeks into it. Namely, loss of appetite. Has anyone encountered this and what to do? Her appetite is abysmal. Its impossible to go on like this. Also, she used to prefer a keto diet, now she just wants crunchy carbs and fruits and sweets.
ReplyDeleteTatjana, weight loss is a known side effect of bumetanide. Did you check electrolyte levels? Is your daughter drinking enough liquids to counter the diuresis?
DeleteOne reader had a problem with BHB causing excessive drinking, but that faded away over time. Unusual reactions seem more common in people with autism.
Here is a comment from another reader with the same problem
https://epiphanyasd.blogspot.com/2018/08/summer-in-city_16.html?showComment=1534758776246#c6692048986800947743
I replied once already but there was an error. If two show up, just delete this one. So, the other reader had a problem with weight loss but same amount of food. we have no weight loss and no energy loss, just not putting food in and changed attitude towards protein snd carbs. for the next few days i will just stuff her with the crunchy carbs she at least wants to eat a little bit of - corn flakes popcorn bread potato chips etc. will see what happens. i have been thinking along the lines of maybe heightened ghrelin to craving for carbs or maybe lack of chloride so lack of gastric acid?
DeleteTatjana and Peter,
DeleteIn my son transient loss of appetite and fatigue while increasing bumetanide dose above 1mg daily was secondary to hydration issues and resolved with increasing the amount of liquids to drink.
Sometimes minor dehydration is not obvious but contributes to appetite or general well-being. Easy way to check hydration in a child on diuretic is to compare his or her tongue look with any other person's. If it is drier than others, that means more liquids are necessary. If your child is young enough and you can get other kids involved, the "show your tongue test" might be a great fun for them.
I have no idea about changing the food preferences.
Here's the anonymous report from a regular reader on a failed Bumetanide trial.
ReplyDeleteDose was 0.5 mg twice daily, time course around 5 weeks, subject 3-4 years old.
Potassium was supplemented from the start at 2×100mg, later 1×100mg and in the end no potassium seemed to be needed according to blood draws on electrolytes. Potassium citrate does not have a child-friendly taste, and I recommend anyone to look for better alternatives if taste is an issue.
Sleep got deeper after 2 weeks, appetite was notably decreased, some more waterdrinking was needed but less than expected.
The trial was confounded by illness (gut flu) in the end, so conclusions are hard to draw. Tried to increase the dose, but after 3 days vomiting occurred and so we went back to initial dose. There was however no cognitive lift at all during the trial and after 3 weeks cognitive abilities hit the lowest point of the year.
Since neither theory nor this trial suggest direct GABA issues, I won't pursue this path anymore unless new data tells otherwise.
/Anonymous
Thanks for the report. It is good for people to be reminded that there are more non-responders than responders to bumetanide and almost all other therapies. So perseverance is needed.
DeleteI think only antioxidants will benefit > 50% of autism cases. Regressive autism due to mitochondrial disease also appears not to respond to bumetanide.
Good luck finding what does work.
Hi Peter,
ReplyDeleteWas hoping you could help please. I ordered bumetanide from Mexico and am going to trial on my non verbal ASD son who is also awaiting TSC testing and MRI. He is 3.7 years 17kg.
I tried to get him on the UK trial but currently only recruiting older age bracket. Could you please answer the following for me....
1. Are there any pre indications that this treatment would be effective. Ie my son has very high gluatmate levels 3 x that which is consideted high? Primarily uses peripheral vision and was born by c section or other if any.
2. Once you start what would you expect within what time frame to show your child is a good responder. Once you know the child is a responder would you then try to perfect the optimal dose with the right balance of potassium fluids etc to get optimal results. If not responding greatly after how long would you discontinue.
3. As for potassium do you get better results giving less. Otherwise I was going to give potassium 100mg twice per day with each dose.
4. Has it helped improve expressive language at all in any non verbal subjects do you know?
5. Also doctor on the trial briefly mentioned it helped with up take of nerve growth factor which is great for learning new skills and learning language. Is this only occur in subjects with high chlorine levels in brain once they come down??
6. Anything I or drs could see on MRI to check if he would be a good responder??
I know its alot of questions but would love to hear your insight.
Many thanks
I think everything you and your doctor want to know is in this post:-
Deletehttps://epiphanyasd.blogspot.com/2019/06/the-safe-use-of-bumetanide-in-children.html
also available as a PDF file to download:
https://drive.google.com/file/d/12OY1kOaM8QrdYE_Ln9dRTYcQP8nILJEJ/view
In regards to TSC there is research suggesting it is effective.
Bumetanide As a Candidate Treatment for Behavioral Problems in Tuberous Sclerosis Complex
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596068/
There is emerging evidence that following bumetanide microstructural changes can be seen on MRI scans, but I doubt most people will look close enough to notice.
https://www.frontiersin.org/articles/10.3389/fneur.2019.00483/full
If anything is not clear having read the post/PDF above, feel free to ask again.
Thank you so much Peter this is really helpful and informative.
ReplyDeleteMuch appreciated.
Hi Peter,
ReplyDeleteI had a read through what you sent me. It all looks very promising indeed. Hopefully, my son will respond positively to this treatment.
I just wanted to ask if you are aware of the Leucovorin trials. We worked up to 45mg and also added mb12 shots. We done so for over 3 months now we have noted marked improvement in cognition, sleep and following instructions. However, eye contact, restricted interests and social interactions still remain a problem. We have not had any improvements in expressive language even though he has said some words in context on a odd occasion during his life he remains mostly mute and finds it hard to get words out. I wondered if you might have any insight into why this may be or if you think there may be hope for improved expressive language with Bumetanide??
He has had ear infections and grommets and a clear ABR and he hearing is not a problem
Also looking to find the right potassium supplement some contain chloride and some are better for rehydrating. Is there any that you are able to say is preferable or should be avoided. Trying to find one that doesnt taste too awful.
Sorry to keep picking your brains on this but its really helpful to have your insight.
Thanks
Clare
Clare, yes I am familiar with Leucoverin. It seems to work well for some people and those people often seem to also take mb12 and NAC. Are you using NAC? I am a big fan of NAC.
DeleteBumetanide may well help speech as it improves awareness and cognition. You also need to stimulate the desire to communicate, for example with PECS (picture exchange communication system)
You can buy potassium bicarbonate as a powder and add to any drink. it is best taken with a drink to avoid GI upsets. There are effervescent potassium tablets. Some also include magnesium which is a good idea.
Peter,
ReplyDeleteThis is great thanks.
No we havent tried NAC, I will look up the dose required and add. Im in the UK so I dont have a doctor to help me just doing it all myself. We also use pb125 an nrf2 and did Imuno and Bravo for 4 mths last year with little improvement. Tried CW cbd but he would keep spitting it out no matter what I put it on so wanted to focus on Bumetanide for a while but if you think compatable I will do along side Leucovorin mb12 and NAC.
You are right my son shows no desire to speak and if I do not give him what he shows he wants will loose interest and be happy finding something else to play with or what have you. We are starting pecs now but have tried natural language facilitation for some time with little improvement apart from cognition. He is a hard nut to crack.
All your advice been great. I will up date you once we have spent enough time on treatment to assess results.
Am at a loss as to know how to increase his desire to speak I was hoping lifting the fog might help.
Also ordered vit A as was going to try the 2 day 200000iu protocol before starting bumetanide as he has gi issues ear infections and poor eye contact doesnt respond to name but can hear fine.
Alot going on will space it all out so can judge results.
Thanks Clare
Hi Peter,
ReplyDeleteMy bumetanide from mexico arrive and I am keen to start. Still struggling to find the right potassium and magnesium supplements that dont contain chloride or calcium. Can you please tell me which brands you are using?
Also my son had and arranged MRI last monday under sedation but the sedative they used chloral hydrate made him restless and aggressive it took over 2 hrs to get him to sleep and he woke as soon as he was put in the MRI machine do you know if this may be an indicator that bumetanide may be successful for him not sure if chloral hydrate is a similar sedative to those indicated to have a reverse action in those who retain high chlorine from birth?
Thanks
Clare
Clare, I found this about your son's sedative:
DeleteThe metabolite of chloral hydrate exerts its pharmacological properties via enhancing the GABA receptor complex and therefore is similar in action to benzodiazepines, nonbenzodiazepines and barbiturates.
So I would say his odd reaction suggests a problem with GABA and it may well be an indicator of a bumetanide responder.
You can buy Potassium Bicarbonate as a powder from Amazon and measure out the dose you want. They also sell very cheap micro scales (pocket sized electronic scales) allowing you to weigh small amounts. 1.2 g of potassium bicarbonate contains 500mg of potassium; it dissolves in water.
I do not live in the UK and my potassium effervescent tablet is not sold there.
Peter thats really interesting to know because it certainly didnt sedate him to say the least and when he did fall asleep it was due to exhaustion I think more than the sedative. I know his blood glutamate is very high so looking forward to seeing some positive results methylb12 shots did very little for him.
ReplyDeleteI also brought the NAC you suggested.
My son drinks like a fish always would eat 4 bananas a day plus the potassium and magnesium do you think its too much to go up to 1mg twice a day in a 17kg 3.8 yr old if I am vigilant with keeping his potassium mag levels up and very well hydrated
Also is there any fb groups on this yet was going to do some before after videos
Clare
Clare, it is very hard to consume too much potassium via diet, most people consume far less than the recommended amount (3.5g in an adult = 7 bananas). In most people bumetanide causes substantial diuresis within the next hour and a half, this causes a drop in blood potassium levels. In most people a small supplement like 200mg of potassium given with each 1mg of bumetanide is enough, in addition to the dietary potassium.
DeleteThere are autism groups on fb. You would have to look for a good one.
Ok Peter, thanks.
ReplyDeleteI started him today on 1mg per dose with 160mg potassium per dose and plenty of fluids he seems fine so far still waiting for my magnesium to arrive. I will order a better potassium supplement that you suggest.
Definitely passing alot more urine 30 mins and there after bumetanide. I plan to keep giving alot of extra fluids and keep monitoring him but his mouth appears moist still but may be harder to keep him that hydrated with the x2 daily 1 ml dose long term. I can always drop it down to .5mg if I think he seems more hydrated. I really appreciate your help. I looked at diff groups and asked about in the TSC groups no one seems to be aware of bumetanide really so I posted some studies and explainations but noone is really mentioning it at autismOne all about CBD and lymphatic drainage which we tried before with little improvement.
Thanks again
Clare
Hello,I'm new here. Thanks for the blog (it is brilliant!) I have a son (4 years old) with "aggressive" ASD. I just discovered the topic of bumetanid.Could you tell me how you deal with shopping? Where you buy IT? We live in Poland. It is not available here. I have already checked Germany and the Czech Republic but it is extremely hard (pharmacists- no one knows..)
ReplyDeleteMaia, I am told that Bumetanide is available in Austria, but you will need a prescription from a doctor (it can be a Polish doctor).
DeleteOur reader Agnieszka is a doctor in Gdansk. It is highly preferable to have a doctor helping you.
In Spain Bumetanide is called Fordiuran and if you ask nicely the pharmacy will sell it to you without a prescription.
It looks like many people buy online from Mexican pharmacies, where it is called Miccil.
It is widely available in the UK and is cheap. You can easily ask someone to purchase it for you with a prescription (again as said a prescription from your country will also be OK). All the best
DeleteHello Peter
ReplyDeleteThank you for your express reply. I quickly found the right pharmacy in Austria. Now they are waiting for the green light to order a medicine for us. Unfortunately, despite intensive research, I have not been able to find a doctor who would help us in the formalities (prescription). I did not expect it to be so difficult .... We get guidelines to wait for the completion of clinical trials. The same answer is everywhere. We feel that we can't wait. My son is 4 years old and we can still do a lot. We know that in a few years the effects of potential therapy may be much weaker. We know the potential risks of using Bumetranide and that we need to monitor and supplement potassium if necessary. We also wanted to start with minimal doses and increase them to 2x1mg when it turns out that the child tolerates the drug well. Do you have a bearing (email) for the Doctor from Poland (Gdańsk) that you mentioned? Maybe she could help us?
Maia, open this useful document on the use of Bumetanide
Deletehttps://drive.google.com/file/d/12OY1kOaM8QrdYE_Ln9dRTYcQP8nILJEJ/view
You will find Agnieszka's contact details in the top left.
I know what biomarker they could use to test the drug.
ReplyDeleteHi Peter, I used Bumetanide starting off as 0.5 mg/ day and she seems to be a responder almost from the start. I increased it to 0.5 mg twice a day after 4 days and she has been more alert and verbal as well as being more open to trying new things as well. However, she also seems to show signs of hyperactivity and curling of her tongue. I think that is an observed side effects so I am now reducing it to 0.5 mg/day again and the gains seems to be reduced. Do you think I should increase the dosage again after a week or two ? She is 9 this year.
ReplyDeleteYou could try 1mg once a day and see how that works.
DeleteRemember to increase potassium in diet and give a potassium supplement. Make sure she is drinking plenty of water. Most side effects appear to be caused by low potassium or dehydration.
Thanks, I am giving her 200 mg of potassium citrate a day now and she’s drinking a lot of water herself
ReplyDelete