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Jumping out of skin. Possibly 5HT2A Serotonin or acetylcholine issue? Benzo or AD withdrawal?

mirtazapine remeron neurotransmitter klonopin benzo withdrawal serotonin syndrome 5ht2a agitation

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#1 PabloHoney825

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Posted 04 March 2018 - 09:57 PM

Hi all,


I recently ended up in the ER twice in the last couple of weeks and am trying to price together why. Since, I feel like I'm still not at baseline. I was hoping anyone with some neurotransmitter experience could help shed some light on what's going on? 


Leading up to these events I was sporadically taking .125 Klonopin about 2-3 times a week, desoxyn 15-20 mg 2-3 times a week, and recently went from using mirtazapine 3.75 mg 7 nights a week to 3-5 nights a week when I suspected PVCs were due to the mirtazapine. Melatonin 5-20 mg nightly with opther supplements like probiotics, magnesium, fish oil, multi-vitamin. Occasionally Valerian, Lemon Balm, Holy Basic etc for rough nights I couldn't sleep without the mirtazpine. 


2/12/18 10:00 pm: Mirtazapine 3.75, Tryptophan 1000 mg, Magnesium Threonate, Melatonin 10 mg, probiotics (66 billion).


2/13/18 7:00 am: Woke up feeling groggy. Took my ADHD med (Vyvanse 60 mg) before work and within minutes knew something was wrong. Way too overstimulating within minutes (high BP and rate- extreme agitation). Took a Klonopin .25 and was able to calm down and make it through the day


2/13/18 11:00 pm:  Started with meditation and binaural beats.  Took my usual dose of Mirtazapine 3.75, Magnesium Threonate, Melatonin 10 mg, probiotics (66 billion). Within minutes I noticed my legs cramping, then my back twitching. I felt depersonalization/derealization. Soon I was pacing the bedroom shivering with a heart rate of 130 and could feel PVC arrhythmias every few beats. My wife took me to the ER. On the way I took a Klonopin again, a .125 mg.  They took my blood pressure upon arrival at 170/110. By the time the doctor came in to see me everything had calmed down to baseline. I had a normal EKG and he discharged me with a prescription for Metoprolol.


Immediately ceased taking Mirtazapine which I suspected may have caused Serotonin Syndrome when combined with Tryptophan. Started Metoprolol but 12.5 mg. Stopped taking Magnesium Threonate but continued with Melatonin and probiotics. Started to take Ambien to replace Mirtazapine but didn’t use every night.


2/24/18: Was able to take ADHD medicine again but at a lower dose. Desoxyn 10 mg.


2/25/18: Took 10 mg Desoxyn and immediately felt overstimulated. I usually take 20 mg. Blood pressure shot up even with the metoprolol and I feared unopposed alpha stimulation so I took a .25 Klonopin and everything returned to baseline.


2/26/18 10:00 pm: Took Doxylamine 12.5 mg, Melatonin 10 mg, and probiotic. Started meditating (yoga nidra) and binaural beats. Within minutes, the exact same thing happened that send me to the ER the first time. I felt depersonalization/derealization. Could feel my muscles seizing and started to shiver and tremble again. Heart skipping beats and went into full-blown panic. Took a Klonopin .125 and went to the ER when my heart started to feel tight in my chest.  I thought this was it. In the waiting room I drank some cold water and it seemed to make it worse. They brought me back and gave me an IV of electrolytes. Again, EKG was normal. Blood work came back normal. Within about an hour I felt relaxed and came back to baseline, which I attribute the Klonopin. Released and told to follow up with cardiologist, which I immediately did. I’m not on Atenolol 6 mg and have an event monitor on the way.  


The next few days were very uncomfortable to where I couldn’t even think. So much adrenaline. Still shaking and shivering, anxiety, weakness, out of breath, palpitations, tachycardia, and high blood pressure.  The Atenolol took a couple days to kick in and when it did it took the edge of and lowered BP and adrenaline.


Possible explanations for what happened or this continued discomfort and agitation:

  1. Considered that all of this could be attributed to Klonopin withdrawal so I stabilized at .125 daily (it was sporadic before so could have been interdose withdrawal).  I’m much more comfortable but not nearly at baseline. I’m preparing to do a slow-taper off the Klonopin.
  2. Mirtazapine withdrawal since I also used it sporadically before first ER visit and then ceased after first ER visit
  3. Serotonin Sensitivity/Syndrome: Tryptophan and Mirtazapine will do this alone when combined. ADHD meds also increase serotonin. Melatonin also works on 5HT2 receptor as does magnesium. Doxylamine does too I think? Meditation also increases serotonin. If this is from serotonin toxicity, why do I still feel amped up weeks later though?
  4. Been taking high doses of melatonin for a couple years. From what I understand the pituitary produces ACTH which causes hyper-arousal. Perhaps when I stopped taking melatonin my this caused the pituitary to react in some sort of withdrawal or dysfunction and causing excess ACTH and this agitation I feel still.
  5. Possibly 5HT2A sensitivity/dysfunction, acetylcholine or histamine issue. Mirtazapine, which I took the first time, at 3.75 works as an anti-histamine (sedating) and has     anticholinergic properties. This is very similar to Doxylamine (Unisom) which I took the second time. I swear that within minutes of taking each these symptoms started. The nervous system uses acetylcholine to calm down so perhaps I have a pre-existing condition that is causing sympathetic agitation (Klonopin withdrawal, mirtazapine withdrawal, Excess Serotonin, overactive thyroid etc.) and when I took these two medicines they suppressed the para-sympathetic system’s ability to compensate. Perhaps I am now flooded with histamine? I'm shooting in the dark now lol. 
  6. An adverse effect to meditation which can and does happen in some people

Thanks for any knowledge you can give

#2 Lieutenant

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Posted 08 April 2018 - 10:42 PM

Hi Pablo, I'm curious to know how you're doing now? Are you still taking the Atenolol? I read in another thread that you tried taking Propranolol for a period, was that any more effective at controlling your symptoms?


I have been experiencing a state not entirely dissimilar to yourself and think we could learn from each others experiences.


I think it's worth considering what you have experienced and continue to experience may be a form of compounded akathisia. Mirtazapine on it's own can induce akathisia, as can benzodiazepine withdrawal. In this case it's not any singular neurotransmitter that is responsible, but the neurotransmitter ratios.


Firstly, the inconsistent dosing of the Klonopin, the inconsistent dosing of the mirtazapine and the use of amphetamines will all make you far more vulnerable to excitotoxicity and neurotoxic side-effects in general. I am not chastising you for this, it is easy to make these polypharmacy mistakes, especially when the substances in question are prescribed. But it is important to establish that this regime is a significant factor in what you have experienced.


I think the trigger was the combination of the mirtazapine and the tryptophan, which elicited a minor from of serotonin syndrome and an excitotoxic state. I believe you likely slept through the more overt symptoms that would have made this easier to identify. When you took the Vyvanse this would have elevated both serotonin and glutamate, causing the recurrence of excitotoxicity. I expect you're aware of why the Mirtazapine and Desoxyn would cause subsequent reactions. I think that it was the melatonin that elicited

your most recent episode through it's serotonergic interactions, given that your neurology was already in an extremely fragile state. I know from personal experience that is has the potential to cause this kind of agitation.


Increasing GABA will certainly help offset the excessive glutamate activity. I think you're following the right course of action by stabilizing on the Klonopin and then trying an extremely gradual taper. Inconsistent dosing or long term use will just exacerbate your condition.

Beta-blockers have well documented efficacy in akathisia and physical agitation in general so they're certainly a good choice to help alleviate your symptoms.


I would recommend you try a magnesium supplement for NMDA antagonism. I would start with the oxide form initially to minimise the potential for an adverse reaction. Taurine is also extremely useful in mitigating excitotoxicity, try and find a product with minimal excipients to reduce potential confounding factors. Your reactions to these supplements will help give us some insight into the nature of your condition.


Let me know how you're getting on anyway. Hope you're feeling a bit better at least.

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#3 PabloHoney825

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Posted 10 April 2018 - 05:22 PM

Hi Lieutenant,


You made my day. Thanks for taking the time to reply to my post. I’m struggling, but functioning—able to work, which is what I'm most concerned about with a baby on the way. I’ve tried a few different beta blockers- Atenolol (OK for symptoms, better for sleep and less side effects), Propranolol (great for symptoms, not so great for sleep and more side effects like nightmares), Bisoprolol (currently testing it out soon, tried it once and it was heavy- very sedating), and Metroprolol (OK at symptoms, and impacted sleep).


I got my lab results back from my endocrinologist, and everything is normal but my epinephrine is 81 (high). Makes sense and explains the akathisia.


You think it was the melatonin for the most recent episode, not the doxylamine which hits HT receptors like mirtazapine (first bad reaction)? I ask because I would love to sleep and could use doxylaime or its cousin Diphenhydramine. I would kill to be able to take these and actually sleep. Do you think it’s worth a try with a very small amount of I’d be taking a big risk?


I’ve been taking melatonin 300 MCG a few times and while it does make me feel funny/slightly ill and make my HR go up for a bit, it helps for an hour or a few with sleep. I’m scared to take more than 1 gram. Holy Basil calmed me but didn’t induce sleep. I’m averaging 5 hours of sleep a night. Last night was 0. Hypnotic jerks keep waking me each time I’m about to dream.

Magnesium seems to ramp me up a bit. I’ll have to try taurine but am scared- maybe a tiny dose. I’ll pick some up this week.


I’m torn about the Klonopin. On one hand, if this is K withdrawal, then I’m helping by slowly taper off. I’m uncomfortable ALL the time though. On the other hand, if it’s Mirtazpaine withdrawal, I’m just adding more problems by taking the Klonopin. I’ve had a few (6 out of 44 days) where I had a major paradoxical raction to the Klonopin—mostly more sever agitation, insomnia, burning, and akathisia. Most of the time, the Klonopin ramps me up a little and makes my symptoms slightly worse but I’m afraid to do any big cuts and cause more issues.


I have a ton of Gabapentin if I decide to cut the Klonopin faster or to help with sleep. Perhaps it will answer the glutamate question, but then I'm sensitive to every medication now and hate to make things worse. 



I’ve included an excel sheet with my Klonopin taper. The C column shows my cuts in ML (I mix it with milk). I’ve highlighted big cuts in yellow (.5 ML or more). Next to this is my symptoms ratings for Pre-Klonopin for the day, post-Klonopi for the day, and total for the day, and also sleep. I highlight in red bad events, and green is positive. Maybe you’ll see a pattern I’m missing. I’m trying to decide if I should go faster, or slower. Either way, thanks again for real—you don’t know how much this all means. I’ll reply faster this time, I’ve been offline for a few days.You mentioned you went through something similar—how are you?  


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#4 PabloHoney825

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Posted 10 April 2018 - 05:29 PM

It won't let me attach the excel sheet...This dropbox link should work...





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#5 PabloHoney825

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Posted 13 April 2018 - 01:37 PM

Sent Yesterday, 09:31 AM



No worries I completely understand. Some days I can barely function although it does seem to be getting better. I'd love to learn from eachother--we are in this together brother. I'm having all sorts of adverse reactions too. I'm seeing a neurologist, endocrinologist, psychiatrist, and will see a nephrologist. I got some labwork back and my epinephrine was high, creatine was high, metanephrines and normatenephrine were also high on one test and not on another. This could all be related to an adrenal tumor but I'll have to wait for my endochronogist to see what she thinks. It could also just be a withdrawal playing havoc with my hormones and transmitters (and glutimate). By the way, I've started a low-amine and glutimate diet and it seems to help keep my symptoms more manageable, perhaps it may help you too? 



By the way I'm going for genetic testing to see how my enzymes metabolize medicines and see if anything is going on there. It may help you to try the same? 


I'm hoping you recover and heal and I'm really sorry you're suffering. 




Also tagged with one or more of these keywords: mirtazapine, remeron, neurotransmitter, klonopin, benzo, withdrawal, serotonin, syndrome, 5ht2a, agitation

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