2 replies to this topic

[Sleepy_Head]

I have been prescribed 15mg of Mirtazapine to be taken daily at night to treat insomnia (sleep disturbance).

 

I have since discovered that Mirtazapine is classed as an 'anticholinergic' drug, and taken over time, could increase the chances of developing dementia.

 

Could someone please advise whether supplementing both Alpha-GPC and Citicoline/CDP-Choline in the morning, would help to counteract the anticholinergic side-effects in the long term?

 

Or would doing this simply decrease the effect of Mirtazapine, i.e. would supplementing cancel the effects of the medication?

 

Many thanks in advance.

 

Arimor

[graatch]

Yes, I think there's more than a bit to the line of thinking. Citicoline effectively increases both brain acetylcholine and its binding, along with its various other properties which seem to be protective against a large variety of neurotoxic insults and processes -- including by inhibiting the deposition of beta-amyloid which is obviously a dementia concern of some kind. (I'm sure it's unnecessary to say that I mean beta-amyloid is a dementia concern, not preventing it.) One potential complexity that occurs to me is that mirtazapine (like the majority of the anticholinergic pharmacopaeia that is also antihistaminergic, from OTC antihistamines to tricyclics and antipsychotics: there are structural reasons for this) appears to have a stronger effect in antagonizing muscarinic acetylcholine receptors than the nicotinic. Because nicotinic and muscarinic acetylcholine compete with each others activity to an extent, it may be that a created imbalance not only from the acting drugs, but from the subsequent regulatory changes (dishevelled nicotinic-muscarinic receptor sensitivities) that may be part of the undesirable effect with regards to long-term neurological health with anticholinergics. That said, acetylcholinesterase inhibitors without a strong preference for sparing nicotinic or muscarinic acetylcholine binding are in fact how you effectively treat anticholinergic poisoning. [1] If increased dementia risk with anticholinergics taken chronically is in fact a matter of some of the same neurotoxic properties as with anticholinergic poisoning in overdose (or recreational use of datura, etc.) then it would seem to follow that there's little problem with exaggerating regulatory imbalances -- especially with citicoline, which primarily increases brain acetylcholine by increasing synthesis rather than impairing its breakdown. I personally would be happy proceeding with supplementation.

 

[1] And vice versa, but poisoning with irreversible acetylcholinesterase inhibitors has much worse long-term effects for survivors than vice versa even if they were given the anticholinergic antidote. Whereas phygostigimine clears anticholinergic poisoning right up, relatively speaking.

Edited by graatch, 08 September 2019 - 02:03 PM.

[graatch]

One more thing. For sleep acetylcholine transmission wants to exist in certain bounds: not too much, not too little -- just like the brain itself, with its cycles of greater and lesser awareness during sleep. Like shutting off too much for too long is bad and not shutting off is also bad. 

 

With physostigimine memory consolidation that would occur in sleep gets abolished in rats. Certainly insomnia can result from acetylcholinesterase inhibitors and acetylcholine precursors taken at too high doses. There are studies showing that citicoline does not impair sleep over time in human study subjects -- but perhaps taking larger doses could do so. People's reported experiences on forums like these would support that. We also should consider here that an acetylcholinesterase inhibitor, preventing acetylcholine's breakdown, is intuitively and definitively more disordering to normal function than providing precursors, whose further use would be regulated by any number of secondary systems. There would be an especially marked difference with a very powerful acetylcholinesterase inhibitor like physostigmine  -- perhaps as well with an irreversible one, like many organophosphate pesticides and nerve gases.

 

For practical use this is mainly meant to say that for this purpose, I wouldn't try and overdo the doses, nor would I be too forceful and combine it with one of the plants/supplements that among their effects inhibit acetylcholinesterase, e.g. bacopa monnieri, ginkgo biloba, and coffee.

Edited by graatch, 08 September 2019 - 04:13 PM.