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Wednesday, 2 April 2014

Clonazepam Dosage and Effectiveness in Autism


Much research is based on experiments with mice rather than humans, for obvious reasons.  This was the case with Dr Catterall’s recent successful trials of a long established drug called Clonazepam, in two mouse models of autism.

Well, it turns out that his findings are applicable to humans.

With a dosage of around 1mcg/kg (that is micrograms per kilo) twice a day, the same kind of positive behavioural/cognitive changes Catterall found in mice are indeed evident in some humans.

The question remains as to the long term effect of using this drug; in very much higher doses, there are negative consequences.


Comparison with dosage for other conditions

·        As a treatment for seizures, the maximum dosage in children for 0.2 mg/kg/day

·        As a treatment for panic/anxiety the typical adult dose is 1mg with maximum of 4 mg

·        For bipolar disorder in adults the maximum dose is a hefty 20 mg

Clonazepam use in the above conditions is associated with both tolerance (gradually needing a higher dosage to maintain effectiveness) and being habit forming (addictive).

The autism dose appears to be just one hundredth of the maximum pediatric anti-seizure dose and is perhaps too low to cause problems. 
 
Increase in Serotonin
Not only does Clonazepam affect the neurotransmitter GABA, but it has a known secondary effect on serotonin, the “happy hormone”, which appears to be low in the autistic brain.

In the US the trade name is Klonopin and it appears to be called “K-pin” among those who abuse it, for the happy effect.
In most of the rest of the world it is called Rivotril.

 
Just how dangerous is Danger Mouse?  (in tiny doses)
Nobody knows.
 
 

38 comments:

  1. Tried Clonazepam 0.025mg in one dose, in the evening, before sleep. After whole 3 days, as you predicted, change was amazing - she become self confident, a bit naughty, but in some joyful, playful way. Started to play more often with friends (by report of teacher end assistant in school). They both reported that she is different, but in good way, even she is harder to manage with (i didn't tell them about new therapy in that time)
    Started to play differently, not in pattern she's developed over the years (she has great imaginations, wich is a plus, but has stereotype of ideas in the play).
    First of all, we noticed that she is capable to sense odors (she had some kind of anosmia before), than she managed to catch a rhythm to dance (that was a real wow!).
    She was speaking with people in the shop (briefly, but adequately)...
    There is much more...

    Change is still present, but after three weeks are slightly paler . There are not so intense. I'm still overwhelmed, just wont to know if I am missing something.
    Do you have some tips, Peter, please?

    P.S. Thank you, thank you, thank you....

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    1. The logical next step is to add bumetanide, which has a greater effect but the same mechanism (making gaba inhibitory). Also vary the clonazepam dosage and time of dosage to maximize the effect. I give it in two or even three doses.

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    2. Can you both relay how you've been divided the Clonazepam dose? Are you starting with a 1 mg tablet and diluting in solution or do you have a scale sensitive enough to get down to 1/40th of a mg? Thanks.

      Neil

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    3. Neil, you dissolve the tablet in a 100ml medicine bottle, Mix very well, a cheap hand held electric frappe mixer is very useful, it fits inside the bottle. Then use a syringe to measure the dose you want. The tablet does not dissolve very well and you get a suspension. But this method does work. Keep the bottle in the fridge. A single daily dose is the simplest method. It takes three days to reach a steady level in the body, due to the long half-life of clonazepam.

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    4. Hi Peter, sorry my math is terrible. So 1 mg pill in 100 ml of water...
      then 1 ml = how many mcg? I'm sorry!!! I should know this probably!!

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    5. Audrey, 1mg = 1,000 mcg. So in 1ml you have 1/100 th of 1mg which is 10mcg

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    6. Hi! I just want to check my math with you for the dosage. I have a .25mg tablet of clonazepam. I dissolved in 25ml of water and then gave my son 2.5ml of water for dosage of .025mg ... My son is 14. 6 feet tall Thanks in advance!!!!

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    7. Your math is fine you gave 1/10 of a pill. I think you will need a slightly higher dose. I use 0.03mg in a 14 year old weighing 55 kg. It is weight rather than height that usually matters. Recalculate your dose and give this higher dose for 3 days. That will produce a stable level in his blood. If he becomes anxious or aggressive your dose is slightly too high, so reduce it slightly.

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    8. Do you believe it would be worth a try for an Apsie to try this even though they found no results through Bumentanide 2mg after taking it for 3-4 months? I happen to be more of the anxious type in terms of the different kinds of Asperger's with a pretty decent social awareness even though I have no ability to read facial expressions or body language pretty much whatsoever. So far I haven't really seen much benefit from substances pertaining to GABA aside from alcohol, I've even tried the benzo Etizolam before with a minimal benefit at best. Although I have tried taking Phenibut more than a couple of times and only once did I feel a relaxed, smoothed out feeling that surprisingly took a few different attempts to achieve, pretty strange that this only happened once and it wasn't even my first time trying it.

      Btw my weight is around 80 kg so if I were to take 80 mcg would be a good dose to try out?

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    9. The dose of clonazepam is so small, it appears to be free of any harmful long term effects. So it is worth trying even though the chances of it helping may not be high - there is no way to predict responders.

      The feedback I have received suggests that most responders find an even lower dosage optimal.

      In your case I think 50 mcg is the place to start. You will reach a stable level in 3 days, so in 3 days a responder would see a benefit.

      Another GABA drug that some Aspies respond well to is Baclofen at lower end of the regular dose. However some other Aspies have a negative response.

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    10. Thank you for sharing your knowledge, Peter. Also I have been looking into Baclofen as well as Pantogam Active but I believe I will be trialing microdosing clonazepam first. Btw what would be considered a lower end regular dose for Baclofen?

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    11. There are people using Baclofen for anxiety but the big off-label use seems to be regarding alcohol addiction (sometimes with anxiety).

      There were a series of comments on this blog from a UK paediatrician who discovered Baclofen helped most of his/her Aspie patients. As usual, she did not give a comprehensive explanation, but the key point was she found no long term problems. Sometimes you have to increase dosages to maintain the effect, this was not the case.

      She did not feel she could continue long term prescribing without some scientific justification, she was worried about getting into trouble with the medical regulator, hence anonymous.

      I would have thought 20-30 mg a day, split into 2 or 3 doses, would be what that paediatrician was using.

      With large doses you need to start slowly and later stop slowly, to avoid side effects.

      It is always best to find the lowest dose that is effective.

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  2. Hi Peter
    I am going to start on bumetanide first and then clonezapam as the side effects of bumetanide seem to be minimal expect diuresis, I saw a genetist who asked me to stop all supplements before going for genetic testing
    Was worried about the addiction effects of clonezapam , also wanted to share that I showed clinical trial info to neurologist who then prescribed both so u can get them in a liquid form from pharmacy as it is easier to measure with syringe
    Thanks
    BK

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    1. It is good to start with bumetanide. The dosage is very simple.

      With clonazepam the dose is tiny and so I think the chance of side effects is very very low. The problem is that if you do not see an effect, you do not know whether you just have the wrong dose, or the child is just not a responder.

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    2. Actually I wondered that same thing in regards to the suforaphane. I have not been able to figure out the dosing for a 160 lb guy. I have been giving 1 capsule (1.5 g) of Super Sprouts in the morning but wonder if I am going too low.

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    3. Actually I wondered that same thing in regards to the suforaphane. I have not been able to figure out the dosing for a 160 lb guy. I have been giving 1 capsule (1.5 g) of Super Sprouts in the morning but wonder if I am going too low.

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    4. In my son, who is half the size of yours, I am giving a dose twice as large. I would increase the dose and see if there is a significant mood change within an hour. If there is no impact it may be that he is not a responder.

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  3. The results of .5mg were astonishing for me, instantly improving my execution function, mood and outlook. All the symptoms of my Asperger's Syndrome receded. I can't find any trials of low dose Clonazepam using AS adults however. I had to fight very hard to find a doctor willing to trial me on low dose Clonazepam. The results have astonished everyone who knows me well and I know have a supportive doctor. The ignorance about this really saddens me. So much unnecessary suffering and waste of potential because of that ignorance.

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    1. Reading this is very reassuring to me. My doctor literally just prescribed this to me and I'm starting it today. Here's hoping that I don't have a repeat of Concerta (which had been on the "no" list since I was 6....)

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  4. This is heartening. At age 31, I just determined that I have adult ASD. It went undetected for a long time because symptoms often manifest a bit differently in women and even though I didn't know what it was, I always tried to hide any unusual "personality traits" I had out of fear. Just this morning I mentioned to my doctor that I have anxiety and she gave me Klonopin without me even asking (!!) I tried SSRI's before, when I thought I just had OCD/anxiety/depression (no inkling of ASD), and they didn't do much besides dull some of my thinking. I am cautiously optimistic and will post results when I have some.

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  5. And you use water as your "solution" yes?

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    1. Yes, you add the tablet to water and create a suspension. It does not dissolve, you just get fine particles suspended in water. This is why it has to be well mixed, ideally with a hand held frappe mixer which will fit inside the bottle with the suspension.

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  6. Dear All, I have just started reading about this. Can I ask where 1mcg/kg dose is coming from? In Catterall's research the beneficial dose in mice is 0.05 mg/kg. I could not find any information about estimated dose for human. Could you please tell me the source of 1mcg/kg dose?
    Thank you very much.

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    1. The source is this blog (i.e. human experiments). You will see in later posts/comments that an even lower dose seems to be optimal in most responders.

      I would say more like that the "sweet spot" is most likely to be found at 0.5 to 0.7 mcg/kg. Once a day seems to be fine.

      Catterall has said that it should be just a narrow band when it might help. He told one reader he expected the human dose to be about one tenth of the regular anxiety dose. He had no plans for a human trial.

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    2. Peter, is this all trial and error to determine the dosage sweet spot ? Do we start with 0.5 mcg / kg / day and then titrate up to 0?7 mcg / kg / day ? As silly as this might sound how do we know if a particular dose is "working" or not ? What are some immediate effects of a "working" dose (so I know to stay at that dose) ?

      My son is nonverbal and significantly cognitively impaired so he won't be able to verbalize his feelings - this will be entirely on me and my subjective opinion on changes I might see.


      Thanks !

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    3. GRT, you will notice whether your son responds to low dose clonazepam or bumetanide by noticing new behaviors, things he does for the first time, other people would also notice.

      Yes, I would suggest you start at 0.5mcg/kg for three days and then slowly increase until you notice a positive effect. Slightly above the effective dose there is a zone with a negative effect. So if your son shows anxiety or aggression, he is a responder, but your dose is too high.

      Due to the long half-life of this drug, it takes 3 days to reach a stable level in your blood.

      Since this post was published, low dose clonazepam has been proposed for another type of autism.

      It is the case for most readers that their child cannot give feedback on therapies. Only people with Asperger's can really give good feedback. I have figured out which therapies work for my son, even now this is the case. I take input from his teachers and assistants who tell me when he does something remarkable. I do not tell them when I start a new therapy, because I want unbiased, unprompted feedback.

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  7. Hi Peter, I am actually a psychiatrist and might plan a study in this. I thought he Prof Catterall was planing a research too. But he might have changed his mind, not sure. Yes he said that it would be roughly 1/10 of the anti- anxiety dose. But anti anxiety dose varies between 0.25-4mg although people needing 4 mg are usually very high in anxiety and even can be described as agitated. So I would say that the typical antianxiety dose I would prescribe for my patients would be around 0.5 twice a day.
    If I plan a study, it has to be on adults though, as I'm an adult psychiatrist. I'm sure adults with Asperger's would love to help. Only pitfall is that majority of them were already given a benzodiazepine before they come to a psychiatrist, so their gaba receptors are not benzodiazepine naive.
    I will take your therapeutic window suggestion 0.5-0.7mcg/kg into account. It is so sad that science leaves people alone and doctors and scientists are not that motivated for research. This could be a basic reasearch for example, not too complicated.

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    1. Good luck with your study. If the dose is slightly too high, there is a negative reaction with anxiety and aggression. It takes three days to see the effect, due to the long half life. I use a single daily dose, but a US doctor reader of this blog finds it works better for his son when the dose is split into two daily doses.

      Another drug nobody is trialing is the standard baclofen drug. A UK pediatrician left some comments about how many of his/her patients with Asperger's responded very well, but without any formal study published did not want to keep prescribing it and did not want to their own study and publish the results. Rather sad.

      Not all Asperger's respond well, but some do.

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  8. Anon... I have aspergers and I tried the low dose clonazepam, it made me arrogant as hell and I absolutely HATED PEOPLE on it, it is not recommended for aspergers in my experience (34 year old adult and been diagnosed since I was like 12 years old).

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  9. I agree with this very much .. my son was not able to sleep on a dosage of 2 mg but when we tried 0.5 he slept the full night, there is something about the smaller dosage in this particular medication, i am willing to give it a try and a small dosage.

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  10. Hi I am an adult with aspergers and extreme anxiety. I want to try the low dose clonazepam and see if i get any improvement. I weigh 150 pounds, (so about 68 kilos). This means I would need a dose of 0,068mcg? Also if my doctor lets me try this, and i get liquid clonazepam, how do i take it? If I drink it wont it taste awful? Let me know thank you!

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    1. My symptoms worsened on low dose clona (I have aspergers), however I do not have social anxiety so I might respond different than you.

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    2. All regular clonazepam seems to come as tablets, for a liquid you would need a compounding pharmacy. The crushed tablet has no taste, the syrup would taste of the syrup base the pharmacy used.

      For anxiety you might need the full dose clonazepam, but at that dose it is an addictive drug. The low dose does not have these problems.

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  11. My daughter is 16 (40kg). I have been giving one 0.5 mg Clonazopam Oral disperible tablet per day for last 15 days. But I see no reduction in anxiety, aggresivenes and panic disorder. Am I giving a very high dosage? Pls advise me the correct dose. Thanks in advance

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    1. This blog covers the micro-dose of clonazepam that corrects a dysfunction present in Dravet Syndrome and some idiopathic autism (the alpha 3 subunit of GABAa receptors).

      The microdose is between 0.5 and 1 micro gram per kg. Most people seem to be at the lower end.

      So a 55 kg child with autism might respond to a dose of 30 micrograms which is 0.03mg (milligrams).

      So your daughter's daily 0.5 mg tablet would last my son 17 days.

      Regular dose clonazepam works in a slightly different way. I presume your doctor is prescribing for this purpose, if so, you should refer back to him/her.

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    2. Thanx for response Sir, My daughter (16yr /40kg) has autism but no Dravet Syndrome. For aggression, anxiety etc, the Dr initially prescribed liquid Fluoxetine 5mg and Arpiprazole Tab 0.25 mg OD.It worked for 4 months but later the intensity and frequency of aggression and anxiety increased. So the Dr. stopped Fluoxetine and added Clonazopam 0.5 mg Oral dispersible tab SOS. But we find that aggression etc increased after this. From this blog we realise we are giving her high dose. We want to try microdose. The Dr is neither aware of this nor is receptive to such new ideas. Pls advise us about the mico dose. Thanx and Regards

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    3. Anjana, anti-psychotics like Arpiprazole (Abilify) seem to cause lots of problems, as do larger doses of Fluoxetine (Prozac). It is much better to find the biological cause of the aggression/anxiety, but this is not easy.

      The micro-dose of Clonazepam would be about 20 micrograms (in milligrams this is 0.02mg). After 3 days a stable level is reached in the blood and a responder would show a benefit. If there is no response you could increase to 25 and then 30 micrograms; if still no benefit than she is not a responder.

      Aggression and anxiety can have different causes and anxiety has many forms; in my son the solution was NAC and Verapamil.

      It looks like many girls with more severe autism do actually have an identifiable genetic disorder, so this is worth investigating (much more so than for a boy).

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