Help Quetiapine dose for sedation, secondary antiemesis

[myopybyproxy]

What dose should be taken if using quetiapine as a sedative? I've seen varying conflicting information - albeit, from the perspective of 'what side effects did you get from your dose' - ranging from 25mg to over a gram. The thread regarding SN - which I am not using, only read up on it to gather as much information as possible - mentions specific dose ranges engage different receptors and mechanisms of action, which I don't understand, but that's aside from the point. I've got 50mg dimenhydrinate (H1 antagonist) as my antiemetic, which I will take orally approximately 35 minutes prior to my last act. But I'm IVing anyhow so vomiting should not be a concern. If I am wrong please correct me on this.

I am taking 80 proof ethanol, some alprazolam and clonazepam - I am sure the benzos are mostly fake, if you are wondering why I bother with quetiapine at all given the rest of my list - some potentiators (full list of potential and currently planned substances in this thread), and oxycodone - ibid - orally approximately 10 minutes prior to the injection. From previous experience dabbling with benzos, they tend to onset quickly, and I don't want to just fall asleep. Or worse, alert someone whilst blacked out and wake up in hospital once again. That is not one experience I would like to repeat.

What is the mechanism by which nausea occurs when taking opiates and alcohol - serotonin, H1/2, D2, etc? Is that mechanism dose dependent or is the property the same regardless, as with SN? I have not been able to find this information online. From the aforementioned SN resource thread, 50mg quetiapine seems to have the same antiemetic mechanism as dimenhydrinate via H1 antagonism, whereas 100mg and 300mg antagonises serotonin (5HT) and D2 receptors, respectively.

I notice a 50mg dimenhydrinate will alleviate weekend-drinking-induced nausea, but this is - although with some potentiators that I plan to use in my method - without the other substances such as quetiapine, opiates, benzos etc. And I have never tested the dimenhydrinate effectiveness when drinking amounts which will give me alcohol poisoning - assuming I don't vomit most of the alcohol before it is absorbed. So perhaps my singular tiny pill will be useless overall. I don't know. Input is welcome.

Furthermore, how far in advance should the quetiapine be taken - assume titration during the weeks leading up to expiry date - specifically the last dose once steady-state blood levels have been reached with the titration? That is, how long will it take for the effects to hit? I am not asking about peak plasma concentrations. Rather, I would like to know at what point the sedative effects begin to impair functioning, ie carrying out the rest of the method. Again, preliminary browsing of anecdotal experiences suggest a range from immediately to ninety minutes. This seems to be dose dependent as well.

If anyone could chime in on this, I would be much appreciative. Subjective anecdotal experience welcome as well as research articles. Any information, please - include as much numerical information as possible in your post - particularly the quetiapine dose and how long it took for sedation to occur.

I know this has been a long post. Thank you for reading the whole of it, if you did. I wanted to give the full background so those giving advice would be able to take it into consideration. In synopsis, my questions:
--> What dose will render quetiapine an efficient sedative?
--> How many minutes before such dose is ingested until sedation occurs?
--> Is opiate and alcohol nausea due to serotonin, dopamine, histamine, or some other mechanism?

 

[NearlyIrrelevantCake]

What level of sedation are you wanting to achieve? Just drowsiness? Unable to stop yourself falling asleep? Etc.

 

[myopybyproxy]

What level of sedation are you wanting to achieve? Just drowsiness? Unable to stop yourself falling asleep? Etc.

That is a good point, thank you. I forgot to mention. Any level of sedation is fine as long as I have 5-10 minutes to prepare an injection and execute it without missing the vein. Ideally then I would be sedated to where I was unable to balance, and would fall off a bridge into water. I am too much of a coward to jump sober.

If it requires long term titration as with for use in SN method, I don't think this will work. I must be clearheaded the first hour or so of my plan.

 

[NearlyIrrelevantCake]

I'll detail how Seroquel sedation works for me. I've been taking it for about 6 years at the same dosage.

First and foremost, the amount of sedation is stronger the longer I've been awake. If I wake up and take my daily dosage, I feel absolutely no effects. I've just slept, I have no sleep debt to pay off, my body will not become sedated unless I take an obscene amount, in the range of grams. If I've been awake for 24H, it can hit me in under an hour and with more intensity.

I'm prescribed 250mg/day and usually take that amount when I'm preparing for bed, intending to sleep in the next 2-3 hours. At that dosage with my tolerance, if I've been awake for at least 10 hours, it will almost always make me sleepy beyond control within the planned timeframe. I frequently fall asleep on my laptop and wake up 10-12 hours later surprised that I'd fallen asleep. I never remember that happening, I just wake up and the last thing I knew I was playing a game or talking to a friend. Sometimes I remember that I couldn't keep my eyes open no matter what I tried.

Sometimes I don't really feel like being conscious [I feel like everyone here understands that...], so I take 300mg to 500mg instead. It hits faster, harder, and I sleep for longer--my record is 22 hours.

You won't need to titrate at all if your only goal is sedation. But I would recommend giving it a test run or two--take it as I do, at bed time. Figure out how much you need for your desired effect, make note of the timeline, etc.

Also--if you're given the extended-release version, just chew it. Mine are the XR pills and that's what I do, even when taking my normal dosage.

 

[myopybyproxy]

I'll detail how Seroquel sedation works for me. I've been taking it for about 6 years at the same dosage.

First and foremost, the amount of sedation is stronger the longer I've been awake. If I wake up and take my daily dosage, I feel absolutely no effects. I've just slept, I have no sleep debt to pay off, my body will not become sedated unless I take an obscene amount, in the range of grams. If I've been awake for 24H, it can hit me in under an hour and with more intensity.

I'm prescribed 250mg/day and usually take that amount when I'm preparing for bed, intending to sleep in the next 2-3 hours. At that dosage with my tolerance, if I've been awake for at least 10 hours, it will almost always make me sleepy beyond control within the planned timeframe. I frequently fall asleep on my laptop and wake up 10-12 hours later surprised that I'd fallen asleep. I never remember that happening, I just wake up and the last thing I knew I was playing a game or talking to a friend. Sometimes I remember that I couldn't keep my eyes open no matter what I tried.

Sometimes I don't really feel like being conscious [I feel like everyone here understands that...], so I take 300mg to 500mg instead. It hits faster, harder, and I sleep for longer--my record is 22 hours.

You won't need to titrate at all if your only goal is sedation. But I would recommend giving it a test run or two--take it as I do, at bed time. Figure out how much you need for your desired effect, make note of the timeline, etc.

Also--if you're given the extended-release version, just chew it. Mine are the XR pills and that's what I do, even when taking my normal dosage.

Thank you very much. From your post it seems that the level of sedation and time to onset are directly correlated. What were the effects for you - and at what doses - when you first started taking it?

Do you suppose taking a nap earlier in the day would allow for a longer lucid period between taking the quetiapine and sedation onset? Or would it reduce the sedation, or do both?

Inversely (conversely?), if I were to deprive myself of sleep for a day or two beforehand, there would be less time til onset and the sedation would be stronger, as per your post. Have you got times? I know they will vary with individual neurobiochemistry and dose - and I do plan to trial, as you suggest - but simply to get a rough idea of the situation here. I have no experience with antipsychotics whatsoever, so any information is helpful.

 

[NearlyIrrelevantCake]

I'm afraid I don't remember that far back--due to another med I'm on, my memory is horrendous. One thing I do remember is that I was started on a higher dose than I'm on now, and it made me sleep for so long [14+ hours every day] that my GP lowered the dose to its current level.

In the rare case that I manage to nap, it entirely resets my sleep clock and I can't sleep again until I've been awake for another 10+ hours. Plus naps leave me feeling awful--I feel like Hell any time I sleep for less than ~10 hours.

I can start to feel a bit drowsy and yawn within an hour on average, but it's not anything intense. I can do everything as normal--cook, run errands if I need to, etc. Just feel tired is all. The exhaustion just builds stronger and stronger as time passes from that point. But it doesn't knock me out until 2.5 to 3 hours after dosing.

 

[myopybyproxy]

I'm afraid I don't remember that far back--due to another med I'm on, my memory is horrendous. One thing I do remember is that I was started on a higher dose than I'm on now, and it made me sleep for so long [14+ hours every day] that my GP lowered the dose to its current level.

In the rare case that I manage to nap, it entirely resets my sleep clock and I can't sleep again until I've been awake for another 10+ hours. Plus naps leave me feeling awful--I feel like Hell any time I sleep for less than ~10 hours.

I can start to feel a bit drowsy and yawn within an hour on average, but it's not anything intense. I can do everything as normal--cook, run errands if I need to, etc. Just feel tired is all. The exhaustion just builds stronger and stronger as time passes from that point. But it doesn't knock me out until 2.5 to 3 hours after dosing.

I see, thank you. If you're awake less than 10 hours, can you take an even higher dose to force sleep? Otherwise I will have to wake up early on the day I die.

So when you take 50-250mg beyond your usual dose, the knockout sedation hits you in 150 to 180 minutes? Is there a gradient you have noticed where 300mg takes a particular amount of time versus 400 versus 500?

Apologies for bombarding you with questions. This has been informative; I truly appreciate your responses.

 

[NearlyIrrelevantCake]

With a high dose, I can manage it at 7-8 hours awake, but it takes longer--sometimes up to 4-5 hours--for the sedation to start hitting. And sometimes the sedation is very weak; I haven't really been able to pinpoint why it's weaker only sometimes.

At a certain point, about 400mg, the sedation for me doesn't hit any faster but it still becomes more intense if I take more than that.

 

[myopybyproxy]

For future reference:

Nausea, emesis, and antiemetics

CONTENTS Rapid Reference 🚀 Differential diagnosis of nausea and vomiting Evaluation Construction of an antiemetic regimen 5HT3 antagonists (especially ondansetron) Butyrophenones (haloperidol & droperidol) ➡️ Phenothiazines (prochlorperazine, chlorpromazine, promethazine) Olanzapine ➡️...

emcrit.org

Teehee, I've found the answer to my third question.

Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems

Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems. Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi ...

www.ncbi.nlm.nih.gov

Opioids cause nausea through the vestibular apparatus. This can be attenuated with H1 and M1 antagonists. Need to get my hands on some phenothiazines.

 

[myopybyproxy]

To answer my first two questions, seeing as how no one else has responded yet, as per @NearlyIrrelevantCake's good idea, I will document my experiments with quetiapine. I've one 400mg. I think it is IR. In any case, I plan to crush it up, remove the outer later, dissolve it - still trying to determine best solvent for this purpose - and dose volumetrically. My milligram scale has been acting wonky lately - up to 9mg off - don't trust it here.

Extrapolating loosely from this research article on microemulsions and bioavailability - could use an oil or alcohol as quetiapine seems to be a polar lipophilic base, fumarate being the more water soluble form but still quite poorly so.

Polysorbate 80 provided greatest solubility to the order of 26.5mg/mL; isopropyl myristate was second with 25.7mg/mL; next were isopropyl and ethyl alcohol at 23.3 and 20.6mg/mL respectively. From a preliminary search, IPM seems most accessible and decently cheap. The alcohols are of no cost to me and I am most comfortable working with them due to familiarity, but they are azeotropic and anyhow are poorest solvents here.

https://www.researchgate.net/profile/Vishnu-Kiran/publication/281114036_Preparation_and_evaluation_of_Quetiapine_fumarate_microemulsions_A_novel_delivery_system/links/55d6bc2f08aeb38e8a840ef2/Preparation-and-evaluation-of-Quetiapine-fumarate-microemulsions-A-novel-delivery-system.pdf

Of note - quetiapine rate of decay* follows zero order kinetics, half life is 7 hours then 11 for active metabolites. Which to consider functionally relevant when designing trials - cumulative total, average, one or the other? It seems the more information I have, the more questions arise.

Conflicting information regarding interactions. These two are my sources. One says cimetidine decreases oral clearance rate by 20%, and conversely, quetiapine decreases clearance of lorazepam by 20% - can this be extrapolated to other benzos? The other contradicts itself - earlier says those two interactions were not present, albeit the latter specified at a dose of 750mg - then further on in the document it concurs with the former source. I will err on the side of caution and assume the former is correct - avoid cimetidine potentiation for the duration of quetiapine trials.

Inactive ingredients include: calcium phosphate dihydrate dibasic, ferric oxide yellow, hypromellose 2910 (6 mPa.s), povidone k30, sodium starch glycolate type A potato, polyethylene glycol 400, microcrystalline cellulose, lactose monohydrate, magnesium stearate, titanium dioxide. I briefly wondered if PEG would be a suitable solvent but it's not mentioned anywhere I've seen thus far so I discarded the notion - sticking to IPM.

To-do list entails:
- prepare quetiapine tablet for dissolution, purchase IPM
- prepare solution with minimal solvent (for the quetiapine alone, requires no more than 16mL based on solubility found by Parvathi et al but I will use up to 21mL)
- trial oral 25mg by volume to be determined, test 10 minutes post ingestion saline IV, take detailed notes
- wait for system clearance*, trial oral 50mg by volume to be determined, T+10 IV saline, take detailed notes
- should a third trial be needed, repeat the above process, adjusting for dose (approximately double the interim period to allow for hundredfold decrease)
- trial mostly complete plan with bioassay experimentally determined dose - two weeks minimum after third quetiapine trial
- based on notes and available data, determine dose schedule for plan

*After 7 to 8 half lives when starting from 25mg the concentration is diminished appreciably by about a hundredfold. Using the lower limit of 7h, this would be a bit over two days. Using the upper limit of 18h, this would be approximately five days. I will opt for five days for the sake of certainty. This is not an area where I can afford shortcuts. I thought I could last time and look where that got me.

 

[myopybyproxy]

Update: almost immediately after drawing up the first bit of IPM, the 3mL syringe I was using became 'sticky' inside - the plunger required a great deal more force to depress and thus was not able to make minor adjustments to the level of liquid within the syringe - only gross movements. Eventually when pulling back the rubber at the end stayed in the syringe and the rod / plastic part of the plunger came out. Over the course of this process transferring the IPM from its packaging to the shot glass containing the crushed quetiapine, the IPM slowly dissolved the dye that marked the measurements, more quickly when I rubbed it over intentionally after I realised what was happening.

Also the quetiapine had a paper wrapping around it, which I could not separate from the rest of the pill and could not crush. Thus due to these two technical difficulties, my test will not be accurate.

The good news is that IPM makes the skin more permeable. And that IPA is toxic and can be absorbed topically. Another add-on...lmao.

 

[myopybyproxy]

Update: finished a full meal T-90. Took approx 250mg propylhexedrine this morning, still feeling slightly off baseline as a result. Texture was odd but taste not as bad as I'd anticipated.

I may have completely misinterpreted the research and chose the wrong solvent. In any case, what's done is done.

T+5 minutes out from approx 1.3mL isopropyl myristate (volumetrically equivalent to 25mg quetiapine fumarate). My process was full of minor errors at every step of the way - thus most likely lost 5-10mg from mechanical transfer. Assuming any of the rest dissolved. I kept the precipitate but have not taken any (don't trust my scale as its calibration has been wonky).

Odd sensation in the mouth. Slight fuzziness in the head - possibly due to remnants of propylhex.

T+10: this is when I planned to IV. Brain been deteriorating lately - difficulty articulating what I want to say. I have planned for there to be 10 minutes between ingestion of the quetiapine and the final step in my method. This may be too short a timespan. I don't feel any sedation as of yet, which is a good thing. Too fast an onset and the most critical step will be a disaster. I'm going to wait another 10 min and then take a minute amount of precipitate from the tip of a toothpick.

T+20: still nothing. Just took a bit of the powder. Eyes very dry and uncomfortable - put my contacts in earlier in case I pass out or fall asleep before getting round to it. The mouth feeling reminds me of lidocaine-dxm cough drops, the way my tongue went all numb and fuzzy.

T+45: slightly more foggy or sleepy but nothing definitely beyond placebo. Going to go to sleep in 5 min. Maybe taking it on an empty stomach next time will make a difference.

 

[Foresight]

Are you ctb tonight?

 

[myopybyproxy]

Are you ctb tonight?

Nope, I'm trying to figure out what dose of quetiapine I should use for my plan. Internet wasn't giving a straight answer and anyhow individual metabolism etc varies.

 

[myopybyproxy]

Update: finished a full meal 1845 T-280 min and am now starting to feel stomach has mostly digested the food. Wish I pushed up the process by several hours. Staying up late messes with...well, everything.

T+0 (2325): ingested about a sharpened lead pencil tip of the nondissolved powder and ~2.7mL IPM solution. Tongue feels weird again - fuzzy.

T+15: difficulty typing accurately, head feels fuzzy. No sedation definitively from quetiapine yet. Paranoid that the IPM will cause damage even though I've not read anything about toxicity.

T+35: slight localised pressure - rather feeling like I have to burp - at the bottom of my throat. OIly residue or some strange sensation there too. I'm not thrilled about the idea of drinking 7 times this amount.

T+50: vision blurring. Must not panic. That will not help. Could be due to high amount of screen time, poor sleep, new contact lenses settling. Vision has been gradually becoming more suboptimal than usual for over two weeks now.

T+65: becoming drowsy, not irresistibly so - am still awake, after all - but takes unpalatable amount of effort to string coherent thoughts together. Can disentangle this sensation from the usual constant exhaustion - this feels distinctly drug induced. Like suvorexant, or the comeup on some street shit. Going to sleep in 10 min.

T+?? 70 except not actually??: It occurred to me that I have lost track of the time. It's now 0055 and clearly the maths do not add up. I don't know where I went wrong but for reference it took me at least a minute to convert the time to minutes prior to taking anything at all. I fear the topiramate has taken my cognitive function down a notch even stone cold sober. Whatever I'll be dead soon. That's my mantra now. It comforts me and yeah it's fucked but i don't care.

 

[myopybyproxy]

Guess I'll take half during the full test run and half during the real thing.