This post came from a regular contributor to RxISK and DH posts. An earlier comment pointed to something interesting and has developed into this post which should be of interest to anyone who has a withdrawal problem that entails some kind of akathisia.
When I came out of a psychiatric hospital in Summer 2019, I had been on zopiclone for a good 6 months. For most of that time I had akathisia which was made worse by even more drugs heaped upon me. The diagnosis I was given was severe anxiety not iatrogenic akathisia. I know it was akathisia.
Akathisia can be a difficult experience to put words to. For myself the first time it started very quickly after taking Sertraline, which inhibits Cytochrome P450 2D6 and 3A4 both very important drug metabolizing enzymes. I was also taking Nytol, which I much later realized contained valerian which blocks Cytochrome drug P450 metabolizing enzymes this very quickly induced suicide ideation in me.
I had no idea what was going on. I immediately drove to A&E and was pacing up and down going to the loo a lot while waiting. Nothing was done other than a letter sent to my GP. I was told there was nothing physically wrong with me.
Akathisia can also come on in a subtle way so that you may only really notice when you are in bed and can’t relax into sleep. Jordan Peterson described it as if suddenly being prodded with an electric cattle prod. It can change from you thinking it’s manageable to feeling horrific in the space of a meal. This might be because the meal contained food stuffs that inhibited your CYP450 drug metabolizing enzymes. Stewart Dolin considered himself well enough to go to a business meeting lunch and an hour or so after that he threw himself under a train.
On discharge from the hospital, I was given a load of promethazine and just told to take it instead of the zopiclone. I recall the crisis team coming round and one of them saying you should able to come off the sleeping tablets in a few weeks.
These people know nothing about coming off these drugs and just how dangerous it is to do it as fast as that. They don’t listen to your fears. It’s their way only. You soon learn not to argue and just lie.
P-5-P
I was in an appalling state but I was free and able to use a computer to do research. Also knew I had to work fast to find a way to stop myself from going into withdrawal akathisia. It had all happened before.
I had used GP prescribed sleeping tablets and benzodiazepines to stop tardive akathisia – benzo during the day, sleeping tablets at night – that’s the plan said the GP. I ended up in an horrific state and 6 months in a hospital, the GP was put on some sort of supervision after I complained to the GMC.
When leaving the hospital I was also on about 4 other drugs including 400mg quetiapine, and 30mg Mirtazapine. I immediately started to tapering off those in a very slow way, they were going to continue to prescribe them so I devised a method with a jig to hold the tablets and precisely cut them with a very sharp blade. So there was a way out of those utterly vile drugs and a method to do it. My main fear and worry was coming off the zopiclone without going into withdrawal akathisia.
Over the years of this experience, I have come to believe that it is the dysregulation of the glutamate/GABA system that is at the heart of many of these problems and that is what I focused on. Knowing that the active form of B6 was required as a cofactor for the synthesis of GABA I had tried it previously but at a much lower dose 1mg to 2mg and it had no effect.
I did searches for anything including B6 that had been trialled to reduce even stop akathisia, any akathisia and found a few papers/articles using a massive dose of 600mg B6 per day or Pyridoxal-5-Phosphate the active form of Vitamin B6 for neuroleptic induced akathisia.
My research also made me of the view I should not only cut out foods, herbs and spices that inhibit Cytochrome P450 but also foods high in glutamate including MSG. I did this immediately and decided to try 100mg B6 p5p going up in 25mg an hour at a time to see how I tolerated it.
At 100mg. I had a pounding headache but slept, the next night reduced the dose to 50mg, still with a headache but slept. Next night I reduced it again to 25mg I again slept still with a headache. I found that I could cope with one night on 25mg the next on 50mg then back to 25mg without a pounding headache. I came off the zopiclone without going into akathisia. I then stopped taking B6.
The second time I felt tardive akathisia coming on for three days – I had been totally drug free for almost two years and again went to 100mg in 25mg steps an hour in between. That again gave me a pounding headache but stopped the akathisia totally and allowed me to sleep. Since then I have reduced the p5p to between 5mg to occasionally 25mg if feeling a bit agitated and have not gone into akathisia or got close to it.
Research Material
The original article that caught my attention was:
Vitamin B6 treatment in acute neuroleptic-induced akathisia:
Other Resources I checked included:
Vitamin B6 and its Role in Cell Metabolism
Nutritional modulation of cognitive function and mental health
How to Increase GABA and Balance Glutamate
Low glutamate foods can reduce the excitotoxicity in the brain.
Wendy Dolin & Kristina Kaiser on MISSD: Akathisia Forum mention
Vitamin B6 Effective in Reducing Antipsychotic Induced Akathisia
Note
The P-5-P element of this report is the novel and interesting bit. The cytochrome p450 elements are not being endorsed here. They may or may not have some merit in cases like Stuart Dolin’s mentioned above.
annie says
Remarkable findings for you, with B6, P-5-P, and associated papers corroborated, to stop feelings of akathisia.
Quite often, patients are given Propranolol :
‘Akathisia is a common adverse effect of antipsychotic drugs and is characterized by subjective feelings of restlessness. First-line treatment usually consists of propranolol, a beta adrenergic antagonist. However, propranolol does not seem to be efficacious in up to 70% of patients.
This study was aimed to evaluate the effect of vitamin B6 versus propranolol on antipsychotic-induced akathisia (AIA).’
I felt ok swallowing 28 Propranolol, throwing up but well enough to drive a few miles to the dog kennels to pick up my dog. The kennels owner decided to keep the dog for a while. I had bloody bandages on my wrists from self-mutilation a few hours earlier. My neck was chafed from rope.
When I got home, I phoned a friend who insisted I went to A & E where I was given over-dose treatment and ferried across the loch to a general hospital. Again, Akathisia kicked in almost immediately, I guess the Propranolol was wearing off.
Frantically looking for a way to end it all, I tried with a plastic bag in the ward toilet. I spent hours and hours pacing the corridors. No one seemed remotely concerned.
For hours and hours I asked to see a doctor. My Seroxat was at home.
I got the Seroxat very late that night and almost immediately was back to my normal self.
I had hallucinated death, almost achieved death, but death was not meant to be.
I think the point is that Propranolol does not stop Akathisia, except in large doses and then only for a limited amount of time –
The Waves –
The first time it happened was when I restarted Seroxat after a few weeks off it, which had gradually built up to a crescendo so unbearable I begged the GP to send me to a hospital.
The resulting combination of Diazepam and Seroxat did the trick in a mental hospital.
Suicidal ideation on my drive home, without Diazepam, resulted in an Akathisia attack three days later, as seen above.
Why the GP did not tell the psychiatrist about the benzos and propranolol is extraordinary, considering the crisis. Why the psychiatrist did not tell the GP about the Diazepam is also extraordinary.
Country practises, all close together had never been further apart.
Any research done to achieve anything, is very welcome.
Stewart Dolin got it in one “I don’t get it, Wen”
https://www.nytimes.com/2017/09/11/well/mind/paxil-antidepressants-suicide.html
Even today, “I don’t get it, Wen” is a suitable epitaph
But, then, Wen did get it…
chris says
Yes I was given Propranolol it worked for about a day, but they didn’t stop making me take it.
Common sense tells me it may well work well for people in benzo withdrawal akathisia, being as it is what the body uses to synthesize GABA from glutamate. I hope people caught up in this hell try it.
chris says
I hope people who have akathisia or have had it try B6 p5p.
Justin Oxley says
I’m a bit confused, I think valerian is a CYP3A4 inducer, what you don’t want to consume are inhibitors such a Grapefruit or Cranberry juice.
I’m going to try and pick up my prescription of 40mg Propranolol today, I have trouble going outside at the moment so I may have to wait until the afternoon. It’s better if I don’t have to wait in a queue as I find doing that difficult at the moment. I’m just going to divide the pills into quarters and take 10mg in the mornings to begin with.
I have already been taking Vitamin B6 at 200mg a day along with NAC at 800mg a day. I read papers which demonstrated these were effective in preventing akathisia. As I think I have a bit of akathisia currently I will probably find it very difficult to sit still in the hairdressers chair so I may have to get my hair cut at a later time like next week or something.
chris says
Hope this is informative:
https://pubmed.ncbi.nlm.nih.gov/15367385/
“Valerian extracts from the products tested also exhibited a marked capacity to inhibit cytochrome P450 3A4-mediated metabolism and P-glycoprotein transport based upon the ATPase assay.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180645/
“Based on these findings, we showed that valerian extract significantly reduced the CYP3A1 mRNA level. Hence, our results suggest that standardized herbal extract can decrease the CYP3A4 activity in vivo and may participate in clinically significant interactions with drugs metabolized by this enzyme, since the inhibition of the CYP3A4 enzyme causes a decrease of drug metabolism leading to an undesirable pharmacological effect and the appearance of toxic symptoms of overdose.”
“Our findings showed that Valeriana officinalis extract decreases the CYP3A1 expression and may lead to interactions with synthetic drugs metabolized by human CYP3A4 enzyme.”
Justin Oxley says
Thankyou for pointing this out, I just typed ‘is valerian a CYP3A4 inducer ?’ into Google and read the text it returned. I may avoid adding a tablespoon of valerian into my french press and instead add two tablespoons of lemon balm. I haven’t found anything which told me that lemon balm inhibits CYP450 enzymes yet.
I would like to have some software which could go through a large database of the CYP450 herb/food/drug interactions stuff and return me a simple clear answer, it becomes difficult to see the wood from the trees reading these very detailed papers. These days it must be possible to create an application which could do that sort of thing.
I just type ‘lemon balm health benefits’ into Google and see what healthline.com has to say about it, the claims also reference the trial papers which back up the claims.
The trial papers don’t tend to cover CYP450 interactions though which is why I would like to have another tool which does that. I did find one paper which covered the CYP450 interactions which was concerned with herbs which were implicated in producing serotonin syndrome when combined with the different ssri chemicals.
Clare Barett says
Examine.com gives breakdowns on effects of supplements and herbs with links to research on pubmed
Justin Oxley says
Here is a list of supplements that healthline.com suggests might be worth trying out to help reverse peripheral neuropathy.
https://www.healthline.com/health/neuropathy-supplements
I now also drink a concentrated tart cherry juice every day. I dilute about 20ml of the concentrate with about 400ml water two or three times each day and drink it.
Justin Oxley says
I have also seen contradictory evidence regarding curcumins effect on CYP450 enzymes. The paper below suggests curcumin activates CYP3A4.
https://www.nature.com/articles/srep06587
This paper which I have not yet read talks about the interaction of various health foods with CYP450 enzymes.
https://jphcs.biomedcentral.com/articles/10.1186/s40780-017-0083-x
This last paper goes into a rather daunting amount of detail about the effects of curcumin on CYP450 enzymes.
https://www.biorxiv.org/content/10.1101/669440v2.full
I really must try and sleep now please, thanks.
Justin Oxley says
I have now got myself 3 boxes of 40mg Propranolol tablets, there are 28 tablets in each box. I’ve felt quite uncomfortable just recently with akathisia. I would like to be able to sit still properly in my hairdressers chair at Bush Fair, I could not do that currently. I have also had the same problems at the Dentist last year in July. To enable me to have the dental work completed my GP Dr. Nazmul Mohsin prescribed me a few Diazepam tablets which did the trick. I don’t want to have to take Diazepam every time I want to get a damn haircut.
I hope after taking 20mg Propranolol each day I shall be in a better condition around this time next week so I can get my haircut.
annie says
You sound like you are independent of your doctor. In fact, your doctor sounds quite compliant giving you Diazepam and Propranalol and, of course, the Fluoxetine liquid. I assume he appreciates how much you would like to finish the course of Fluoxetine liquid and the problems you are having with the last few drops.
After the first year of withdrawal didn’t go too well, a new young lady psychiatrist contacted a hospital pharmacist who devised the year long plan dropping from 40 mg Seroxat (2 x tablets per day). This started with getting the tablets reduction down and then 12 months of measured syringed Paroxetine liquid.
The last few mls gone, I started to severely hyperventilate again and became bedridden again.
Diazepam was refused. There was no way I was leaving the surgery without it, so after a difficult few moments, this particular doctor wrote in my notes that he was not responsible if anything went wrong and made me sign it.
They didn’t last long, and my mother was at the end of her tether, as were my little girl, her father and even the lab, slinking around with a dropped tail. Mum called the surgery for probably the thousandth time, as I was sinking very fast in to putrefaction.
The lady doctor, who had said it was perfectly ok to go cold turkey from Seroxat the previous year, brought round two boxes of Fluoxetine tablets.
Did she really think I was a complete idiot. Having painstakingly gone through months of Paroxetine liquid, to start again as if the whole ‘Seroxat Saga’ had passed them all by, I took my leave of my doctors and put them in the bin.
I rode it out, mostly in bed for a few months taking nothing but water and a few mouthfuls of food and a bit of fresh air, cajoled by mum who knew what the doctor ordered…
This second withdrawal, although extremely unpleasant, did not contain a whisper of suicidal ideation, delusion or hallucination. I will attribute this to the liquid.
My medical records detail 2/3 years of extraordinarily grave doctors’ delinquency.
My point to you, Justin, is to nurture this doctor of yours, who is giving you what you are asking for and who is not rocking your boat, as you seem to have worked out the best plan for you.
Justin Oxley says
I was thinking about the way that the Butterfly IQ ultrasound devices transducer works. The Butterfly IQ is one of a few portable ultrasound devices on the market which all employ a technique known as beamforming to create images of internal anatomy.
Thinking along these lines it should be feasible to drive an array of ultrasonic tranducers to create haptic stimulation at a given point in space. The idea would be to create an acoustic biothesiometer which could be scanned over any area of the body. The contours of a skin area could be determined using a laser height sensor. To make this idea work you would only need to use a single array of transducers which would be held in a fixed position above the area of skin to be stimulated. Watch the video below to get some idea of what I am proposing.
https://youtu.be/hCC1C5KIeUA
An acoustic biothesiometer would need to scan the stimulus node over the skin slowly in a point to point fashion. At each point on the skin the intensity of the acoustic stimulus would be slowly increased until the patient reported being aware of the stimulus. Acoustic biothesiometry would represent a more elegant method for the subjective assessment of peripheral nerve functionality than the mechanical devices which are currently on the market.
Justin Oxley says
I found this relatively new Neuro Touch biothesiometer device this afternoon, it also covers hot and cold perception testing. I don’t know how expensive it is.
https://youtu.be/-ea6WtA86qI
https://www.yostra.com/#AboutUs
Ruth says
I stopped Paroxetine 18 years ago but still occasionally get akathisia. This affects me as very bad anxiety and I can’t keep still. I started taking 10 mg of P5P a day after 2 weeks it had lessened. I have been taking it for a month now and akathisia has gone.