Off-label medications to improve sleep quality and quantity

Hey Everyone,

So I have been working incredibly hard to optimise my sleep. I find that when I sleep well, life is 1000x better. I want to preface this by saying I include all of the ‘sleep hygiene’ protocols (morning sunlight, no evening light, no caffeine, blue blockers, not late meals, etc etc etc etc). I have great sleep latency (3-5 minutes) but tend to wake up 4/5 times per night. I also tend to wake up very early and can’t get back to sleep even though feeling tired and only sleep 6 hours.

Anyway, my tinkering reluctantly led me down the path of pharmacology eventually. I have addictive tendency so steer clear of sleeping pills. I have added low-dose pregabalin 75mg 1 hour before bed and seen brilliant results. Now only waking up 1x per night. Sleep is much more efficient. I wake up feeling rested - never groggy. The impact has been profound.

I also plan to add trazodone 50mg to my protocol. I hear good things about this drug for sleep (low-dose, non addictive, doesn’t negatively impact sleep architecture, etc).

Curious about anyone else using these or any other off-label Rx to improve sleep quality/quantity? I think sleep is such a foundational piece of the longevity puzzle and is often overlooked because it’s probably the most difficult variable to improve.

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I have suffered with insomnia for over 20 years and, at my worst, have been near suicidal. During that time I have tried every tactic and supplement available with little long term success. 2 years ago, after a particularly bad period, I began taking low dose (7mg) Mirtazapine. For me this has been transformative and, after the first 3/4 days, side effects are minimal.

The long time risks (dementia?) are certainly a concern but it’s still infinitely better than the alternative. Also worth mentioning that my total sleep and sleep architecture has been gradually improving during my time (1 year) on Rapamune. Perhaps, at some point, I will be able to discontinue Mirtazapine…

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Interesting - thanks for the comment. A quick search shows that mirtazapine is not chemically addictive and yields some very positive results.

Improves sleep latency, less wake ups, less light sleep, more deep sleep, preserves sleep architecture at low doses.

Side effects of lack of sleep are also dementia - so with or without the Rx there will be side effects!

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That 3-5 minute sleep latency doesn’t mean its good, usually anything under 8 minutes indicates increased sleepiness that could be a result of an underlying sleep disorder.
Have you gone to a sleep clinic to see if you have a sleep disorder of some sort?
If you are doing every thing like you said you are in regards to sleep hygiene and consistency, then you might have an underlying sleep disorder causing issues such as apnea, insomnia, etc. I do not know your age, if you are older then that might attribute to your sleep patterns , but I would still go get tested. Then after you find the results, that might better help you with figuring out pharmacological interventions.

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Agree about the sleep latency - I am aware of this. I work exceptionally hard and train exceptionally hard so usually when I hit the pillow I am pretty drained. I know that’s probably not ‘ideal’ but I love my life so much I am not willing to pull back from the things I am working towards.

In terms of sleep studies - it’s something I have considered. My Oura ring rates me as restless every night. However, I am not sleeping pretty good. Last night over 7 hours sleep with zero wake ups. I definitely see marked improvement with low-dose pregabalin.

Thanks for the tips definitely got me thinking about the sleep studies again

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Forgot to mention: I am 30 y/o. I was sleeping perfectly until about 1.5 years ago.

There is 1 old 1st generation antihistamine that in the ITP studies actually increases lifespan, all these old 1st generation antihistamines make you very sleepy too. I forgot the exact one though.

Personally I really like higher dose melatonin for sleep quality

Edit: I remembered it’s Dimenhydrinate sold as drama mine in the US

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I will say Oura rings are probably the best device out on the market right now for tracking sleep… but it is still not very accurate( I am sure you are aware of it). Anything that goes on your finger or wrist will not accurately track your sleep.
The best thing is EEG polysomnography (which a sleep clinic will do for you) as that will actually measure your brain waves so they can see your brain sleep states as you transition from alpha to delta to theta waves( Your brain’s transition into sleep stages).

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I take 50mg of trazadone (together with 100mg theanine, and 3 capsules of magtein).

Peter attia mentioned recently that he takes 100mg pregabalin plus 50mg trazadone, 2 grams of glycine, 600mg ashwaganda, and 2 capsules of magtein

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I take 300 mg gabapentin as needed for GAD which can cause insomnia for me - it makes me sleepy after ~2 hrs and I feel refreshed with plenty of deep sleep even with 5 hrs (I aim for 7 hrs, but several times a year that’s not feasible). Some people are non-responders. I avoid pregabalin.

Every day I take Magnesium Taurate 500 mg. Seems to help slightly as well. This is already with sleep hygiene and all.

Please talk with a psychiatrist or sleep specialist. There are a lot of possibilities for why one has insomnia. There are many sleep tracking devices that are pretty meh when compared to the gold standard PSG.

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I don’t think people realize how prevalent sleep apnea is, nor how detrimental it is for health.

There’s an app called SnoreLab that my dentist recommended which can help you self diagnose a problem. If you want an at-home sleep study the Watch Pat is disposable and inexpensive. I got one through a local men’s health clinic.

Anyhow, getting an oral appliance has greatly improved my sleep quality! It advances the jaw which prevents the tongue from falling back and blocking the airway. My score in SnoreLab went down from moderately bad to negligible.

Edit, I’ve had one made by an ENT sleep doc, and it was too uncomfortable to use. It costed nearly a grand and it belongs in the trash. A dentist made a custom one for the same price. Avoid the MyTap device! From experience, you’re better off going to a dentist who deals with sleep disorders.

You may be referring to meclizine, which was discussed in another thread.
It is also sold as Dramamine II

My own experience with it is that it extends sleep time with fewer wake-ups and no daytime sleepiness.

It is a first generation and appears to have no detrimental cognitive effects.

Meclizine / Dramamine II, Approx 15% Lifespan Increase, Another mTORC1 Inhibitor - #11 by Arhu

“The upshots of our study proclaim that meclizine protects cognitive deficits by virtue of its antioxidant, anticholinesterase, and antiinflammatory properties. Results also signify the potential of PXR in neuroprotective actions of meclizine in dementia.”

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Thanks for the comment. Curious to find out why you avoid pregabalin?

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And

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My initial reason for studying medical processes was to improve sleep. If people are deficient in nutrients like Magnesium or Vitamin D3 then supplementing helps.

There are other things that can help. I am a major user of Melatonin, but never to get to sleep. It may be that dihydromyrecetin would help with sleep maintenance in this situation, but sleep is such a complicated process that really more information is needed to make suggestions.

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I recently became aware that this molecule can prevent hangovers. I have some on hand for the next time I’m drunk. I haven’t been able to put it to the test…yet. Any experience with it in that regard?

I have been using DHM and Pantethine when drinking for many months. I srtarted with DHM aka raisin tree and it had a clear positive effect. Pantethine, however, had an additional positive effect. Pantethine accelerates conversion of acetaldehyde into acetate so less harm is done by the acetaldehyde. The vasodilative effect of acetate and increase in heart rate still occurs, however. It can bring forward the alcohol rebound wirh sleep. When i drink (which i have done a lot over xmas, but didn’t last night) i am quite a heavy drinker. Eg a bottle of red wine and perhaps a litre of beer or cider on average. No real hangovers, however.

The danger is drinking more. Pantethine which is a non rate limited version of B5 can increase bleeding and bilirubin. It is a coenzyme a precursor and that has effects.

I normally take 2g of pantethine and 1g of dhm.

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I wasn’t aware of pantethine. A trustworthy source of DHM is a bit harder to find. I had doubts about the stuff on amazon and went with this.

What are the products you get?

I get DoubleTwo DHM 1g from DesertCart and it seems to do the job.

I am in the UK and I get DHM also as raisin tree I think a different dosage I have not got the time to find exactly where from, but it looks a bit like this (from memory it is 600mg rather than 400)

If you would like me to check this out I will.

I get Pantethine (and make sure you get this not another b5 precursor) from Amazon.
https://smile.amazon.co.uk/gp/product/B081ZB4YQJ/

These are 1g capsules. I normally take two. If I am going on real all day bender I might take some more during the day. They don’t affect getting drunk, but they are perhaps more effective than DHM in reducing the harmful effects.

It still disrupts my metabolism particularly I think through the vasodilative effects of acetate for one night although if I finish drinking early enough in the day it is not as bad.

Also my night time heart rate perhaps takes 3-4 days to settle down from the figure in the 60s that I will get when drunk to around 50 or less bp. It normally drops to 54-55 from above 60 the first night then gradually goes down.

Remember alcohol depletes copper and this can cause problems with the creation of red blood cells. If you are a heavy drinker consider supplementing with copper. I take 7.5mg a day and a bit in a multivitamin twice a week and that is gradually picking my copper level up from deficient.

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Systemic side effects (ie weight gain) are much less frequent than pregabalin.

I’d also note the potential of addiction and dependence to pregabalin is higher and thus it’s harder to get in some places.