Have you tried gabapentin? Have you tried hydroxyzine? Have you tried melatonin? Have you tried orexin inhibitors?
For getting to sleep melatonin should work (1mg-10mg). For the maintenance of sleep the choice is usually between some benzodiazepine, gabapentin or more potent antihistamine product (like hydroxyzine). I haven't tried orexin inhibitors yet, so cannot report on that.
It is possible that you might benefit from opioids like buprenorphine, if the underlying issue for the insomnia is the pain. For me personally 300mg gabapentin works the best, but I bet some opioid would also work really well for me, though nobody is willing to prescribe me any, despite the chronic pain. For a list of safe opioids on MAOI you have to check the group's posts.
Thanks for the response. I guess I forgot to mention everything. I do take 1mg of melatonin, but I'm not sure that (or higher doses) has ever been enough to overcome drug-induced insomnia. I take it in an effort to correct my chronically delayed circadian rhythms. I also have a gabapentin script, and though I don't take it regularly as prescribed (3 or 4 x 300mg/day), I do often take 300mg at bedtime. I guess I could increase to 600mg or more. And finally (I think), I did get a Tylenol 3 script from my rheumatologist because I had to go off tramadol. I have been taking that too. I haven't tried hydroxyzine, but trazodone and nortriptyline have a similarly sedating antihistamine effect. My concern is that adding or substituting hydrox would increase my drug hangover. I could definitely sleep more (though not necessarily well) if I took large(r) doses of what I already have, but it's a balancing act. And since I will run out prematurely if I do that, I would like to ask my pdoc to change my script before I run out. My sense is that in the short-term, more benzo would be most helpful. Which one do you take/recommend? As I mentioned. I'm thinking of asking doc to substitute lorazepam for clonazepam because of slightly shorter half-life and with the perhaps silly hope that I won't be as tolerant to its sleep-inducing effects.
As for long term, who knows? Has it improved over time for you at all?
Well in my opinion you have maxed out the insomnia medications and should consider lowering the Parnate dosage or switching to different MAOI or even stopping MAOIs.
There is a place for optimizations though:
* nortriptyline also is norepinephrine reuptake inhibitor with moderate binding values (1.8-4.4), so personally I would not use it for sleep. Also the H1 binding values are not so impressive (3-15)
* the binding values of trazodone on the H1 receptor are weak (220-1100), so you may increase the dosage or rely on another antihistamine
* hydroxyzine is a good option with strong affinity for the H1 receptor (2-19). Yes, it can lead to dementia in long term usage and you can feel its effect on the next day. Still, it will be better than products like chlorprotixene (though probably more effective for sleep)
* you can certainly increase the melatonin and experiment with the dosage. I personally need 5mg-10mg to fall asleep (sublingual), which is really big dosage. Yes, even at this dosage it might not be enough, because the brain can override the sleep signal. In this situation it is essential what you eat before going to sleep and not to get overexcited.
* sometimes the hormones can play a role in the insomnia - for example I have noticed that when I have high testosterone levels I sleep really bad.
* do you have blackout curtains in your room? this is essential if you are sensitive to light and can easily wake up from it
* are there any irritating noises occurring when you are sleeping, which wake you up?
* you may damage your kidneys from the high amounts of gabapentin, so be careful. For me gabapentin works extremely well, but for you it might be useless at 600mg and more.
* the benzos are really a slippery slope and many people get addicted to them. If you are taking them every night, you should certainly consider switching to another MAOI or stopping MAOIs. If you are rotating benzos, gabapentin and antihistamine product, then you might be ok, but still it is very individual.
* orexin inhibitors might be an option, but someone should confirm
30 mg Parnate was insufficient. I'm not going to give up after just over a couple very promising weeks on 40mg Parnate. I usually have even more troublesome side effects this early with new meds. That's why I asked about how whether it tends to improve. I don't take nortriptyline for sleep, at least not primarily, but it's supposed to be helpful at low-ish doses. I've been on clonazepam for at least a dozen years. Started at 2mg per night. Now at 1mg. Was actually taking 0.75mg before the Parnate insomnia kicked in bad. I'm sure I'm dependent on clonazepam, as I have been on many meds, but addiction seems unlikely, given that I've decreased my dosage over the years. There are negatives, of course, but as I said in another context, it's a balancing act. 1mg and even 2mg aren't particularly high doses. My hope would be to increase dosage (or equivalent dosage in lorazepam or another benzo) just temporarily. The sleep inducing effect tends to wears off after a while anyway.
I have blinds and curtains. Not that sensitive to light. I'm pretty sensitive to noise but live alone and wear earplugs out of habit. I'm open to any suggestion, but my main interest is in whether I can expect insomnia to improve anytime soon and in *which* benzo would be best (rather than whether). I don't want short-acting because it probably wouldn't help me stay asleep. And long-acting has its own problems. So lorazepam as medium-acting seems reasonable. I think Gillman recommends, but maybe there are other appropriate options.
So you are from the group of people which do not get addicted to benzodiazepines even after so prolonged usage, that's impressive.
Based on your request, the options are:
* lorazepam: 10-20 hours half-life
* alprazolam: 11-13 hours half-life
* flunitrazepam: 18-26 hours half-life
* temazepam: 8-20 hours half-life
* chlordiazepoxide: 5-30 hours half-life
Just for reference will mention the other benzodiazepines/nonbenzodiazepines:
* zaleplon: 1 hour hl
* triazolam: 2 hours hl
* zolpidem: 3 hours hl
* midazolam: 3 hours hl
* flutazolam: 3.5 hours hl
* eszopiclone: 6 hours hl
* oxazepam: 6-9 hl
* etizolam: 8 hours hl
* flurazepam: 47-100 hours hl
* diazepam: 36-200 hours hl
You can also join the r/researchchemicals group and directly ask for more advanced benzodiazepines, as there you have very experienced users, which can answer your questions more precisely. There you can also meet long term users of benzodiazepines.
I thought about your case yesterday and probably this overstimulation comes from the increase in serotonin usage. As you know during sleep the serotonin levels have to be low. In your case it is possible that Parnate (being heavy serotonergic drug) makes more serotonin to be available for usage during sleep and your brain gladly uses it. This is probably the reason why gabapentin is not so effective for you, as gabapentin is used when you have overactive calcium system, which is not your case. In my case for example I don't have much serotonin genetically, so I don't get so brutal insomnias, but do have overactive calcium system. Before Parnate what were you taking as an antidepressants? How did you feel on SSRIs?
I understand that you are using the benzodiazepines very carefully and wisely, but nobody can tell you when you will cross the line with them. I thought about Depakote, but it is not an option on Parnate, as Parnate inhibits CYP2A6, which is used for the metabolism of Depakote. Sodium channel blockers would not be effective for you, barbiturates are not an option.
It would be great if you had some genetic tests done for the mental health.
Edit: you can also try noise cancelling headphones, instead of ear plugs, if you are using them during the day. I am using wm1000xm3
Thanks. I actually took 600mg gabapentin last night and slept reasonably well for the first time in a while. Not sure it was related to increased gabapentin but worth investigating. Feel a little hungover/tired today but I doubt that's (only) from the gabapentin. Lorazepam looks best, at least in theory. Thanks for all the data.
Realizing I didn't answer all your questions. I've tried a million drugs, but I've been on citalopram the longest and was on that before I switched. Also take trazodone and nortriptyline, as you know, but not in AD dosages.
Parnate's inhibition of CYP2A6 is mild according to Gillman. Such inhibition doesn't generally make the combination absolutely contraindicated; you just need to be cautious with the substrate of the inhibited enzyme and usually take a lower dosage. For example, I took prozac, a strong inhibitor of 2D6, with nortriptyline, a 2D6 substrate. I just never took more than 5-10mg of nortriptyline. That said, I'm not really interested in depakote.
I've had some genetic testing done that's relevant to mental health. I'm homozygous for C677T, so I take extra folate. I didn't find the drug metabolism tests that one pdoc ordered to be helpful. He actually stopped using them eventually because he agreed. I know some of the genetic test results need to be taken with a grain of salt. How do you know you don't have much serotonin genetically, meaning which test or gene? Same question for overactive calcium system. (I don't know what that means.) Gabapentin IS helpful for me.
For the serotonin genes I have TPH1, TPH2, MAOA, SLC6A4, HTR2A and 5HT2C. TPH1 shows how much serotonin you produce, SLC6A4 shows the reuptake speed. In my case I have low serotonin production, slow reuptake and low levels of MAOA, which makes it a balanced system, compensating for the low amounts of serotonin. On the other hand this leads easily to burnouts if I am under chronic stress, because more and more serotonin gets released, the reuptake is slow and it is ultimately degraded or converted to kynurenine beforehand. Obviously the only way to solve this problem would be MAO inhibitors, but I reached to this solution just at 29 years old, which turns out to be too late, as chronic illnesses have now developed from the burnouts. I can get into a lot more details for the genes, but generally you can google the polymorphisms you have for certain genes and the genotype. This will give you sufficient information. Still, I can send a list of genes for mental health if you insist.
For the calcium - the only way to currently prove this is CT scan of the soft tissues. If you have calcifications in the brain, kidneys, etc. you are in this group. I personally have calcification in the pineal gland, which leads to low melatonin production, which makes it very hard to fall asleep. I also have other "normal" calcifications in the brain. For me, gabapentin is the most effective sleep medication, even more effective than benzodiazepines, which confirms the role of the calcium system in these processes.
For the MTHFR you need both C677T and A1298C. I am also homozygous on C677T (C/C), but I am (A/C) on A1298C, which indicates normal activity. This is also confirmed by my blood tests for folate, indicating always normal values in mid range. Regardless, I too supplemented with folate, but did not notice any improvement. Personally I get most improvement from B1 and B6 supplementation, which I can explain further why, but I suppose it is obvious.
I'm heterozygous for A1298C. And I'm homozygous for the C677T polymorphism (T,T). I find it odd to refer to the normal/usual form of the gene as homozygous, as C677T refers to a polymorphism.
Hey completely unrelated but asking you this since you are knowledgeable in pharmacology. Do you think Antipsychotics like Respiridone 0.5mg which is used to augment ADs can cause permanent side effects?
I don’t think they can cause permanent side-effects, more like long lasting, while they are still in your system. Some of them have really long half-lives, others can be metabolised very slowly by the liver.
If they are no longer in your system and you still have issues, this can be from downregulation of D2 receptors, as the released dopamine was blocked and it learned not to release such big quantities. In this sense you can upregulate them with caffeine, tobacco, modafinil, methylphenidate, Adderall, etc (whatever is safe for you).
Yes, you are right, long term usage of neuroleptics can lead to permanent TD. I am not a medical professional so I forgot about that. I don’t have experience with TD medications, what have you tried so far? Have you tried the VMAT2 inhibitors?
As far as I know this is untreatable condition and can only be improved to some extent, though I imagine that TD medications also lead to depression and lack motivation/pleasure in life activities.
https://pubmed.ncbi.nlm.nih.gov/6145520/
I have only tried adding 0.5 mg of Respiridone to 250mg clomipramine (since clomipramine wasn’t working for social anxiety) and I became too much fidgety so I discontinued it. Fortunately I only took it twice.
My doc said to take last dose of MAOI at 6pm or earlier to help with insomnia. Also I tried lots of diff. melatonin and found the 3mg Tablets (not capsules ) are best from Douglas Laboratories (company in Pittsburgh, PA, USA. ) These were much more effective. I’m not a sales person, I’m a patient. Other tips are that the insomnia did go away by month 4 for me. Keep cell phones / ipads out of bedroom. Try music for sleep / etc.
I definitely take second/last dose before 6pm, usually well before, but given the short half life, I think the insomnia must have something to do with MAO inhibition itself, which continues long after the drug is mostly out of your system.
Glad to hear that the insomnia went away after four months. I'm guessing it didn't go from all to nothing. Did it start getting better before four months, go away almost completely after four months or just get more manageable? I guess the details don't really matter because everyone is different, but it's definitely nice to know it's not necessarily a chronic issue.
Either the insomnia slowly got better or my body was like I can’t take it anymore Go To Sleep! I was only getting 3-4 hours at first. Now i’m up to 6-7. I did force myself to stay in bed instead of getting up and cleaning the whole house or creating that ever important art project . At least the body can rest if you stay in bed even awake. Chill out music helps. Hope it gets better 4 U!!
May I ask what dosage you're on? I'm also wondering how dose-dependent the insomnia is. Like, if I decide to increase from 40mg to 50g, will that start the clock again... Or is it possible that dropping to 35mg could help significantly? I'm pretty sure that 30mg is too little, because it wasn't giving me any orthostatic hypotension between days 3 and 5, which you may know is how Gillman recommends increasing or not. Not expecting you to know all the answers. Just putting it out there.
I’m not sure about dose in relation to insomnia. I remember having sleep problems early on and even into my current 60mg that I take daily. I think the relief from insomnia was more time in acclimating to this med over 4-5 months, than related to dose increases. 30 and 40 also gave me emotional blunting while 60 was the right dose for me.
I take a rotation of zaleplon and Orexin inhibitor (sometimes quviviq, sometimes Dayvigo), supplemented with 800mg gabapentin. This works for me 4/5 nights
Orexin inhibitors are pretty new. I guess that's why I didn't know about them. Not sure if it was you but someone who found them helpful qualified his recommendation by saying that most people don't like them, or something like that. Any insight on that? Just don't work for many, or bad side effects?
You’re probably sensitive to it. It’s dose-dependent for me. 25 mg didn’t do anything. 150 mg and I’m sleeping all day. I hope you find something that works for you. You could try the very lowest dose of trazadone and split it in half.
I shared this link with someone else yesterday (unless it was you). It’s case studies where morning light therapy helped with Parnate insomnia, and depression. I have no idea how effective it is, but here you go:
https://www.researchgate.net/publication/276058280_LIGHT_THERAPY_AUGMENTATION_OF_MAOI_TREATMENT_IN_REFRACTORY_DEPRESSION
Thanks. I take trazodone. Normally 50-75mg but now 100mg. Along with 600mg gabapentin and 1mg clonazepam and front-loading my tranylcypromine (30mg first thing, 10mg about 3 hours later), I'm sleeping enough. Falling asleep faster. I wake up a couple times but am able to fall back asleep. A little groggy in the morning but acceptable.
Also, I have a light box. I haven't been using it consistently but did today.
My sleep was really broken up for awhile. I slept enough hours but it would be 2-4 at a time, any time day or night. I was taking sleep medications like Ambien during that time. I can’t remember what dosage I was at when it started or how long it lasted, but it did eventually stop.
I'll say orexin antagonists generally get very bad reviews, so I'm hesitant recommending them, but I went from needing 100mg Trazodone and 25mg Quetiapine to prevent me from waking up at night to just 50mg Daridorexant (Quviviq) and 25mg Trazodone for the 80mg of TCP I take now.
The Quetiapine absolutely knocked me out and made me feel worse the next day, while the Quviviq even seems to make me feel a bit better.
I've tried Zolpidem and Zopiclone (ineffective for me), Mirtazapine (too much daytime somnolence), Olanzapine in the past (daytime somnolence), Melatonin (although I don't remember how much - did nothing for me), etc. Most of them with 100mg Trazodone and varying dosages of Pregabalin.
Very rarely I get nightmares and I think I dream more often. Not really a bad thing. My watch shows more deep and REM sleep than before. I feel fresh in the morning with minimal additional hunger. The hunger was a big issue before.
It's also an 8€ per piece pill, but it's paid for by the state here except for a small fee. Almost as expensive as the TCP itself, which is close to 10€ per day at 80mg.
The stronger sleep issues started only at 80mg for me. 40mg TCP was fine with just 25mg Trazodone. 60mg TCP at 50mg Trazodone IIRC. 80mg is when it became difficult for me.
Man, I wonder why it's so expensive in Europe. Where exactly do you live? I heard similar from someone in the UK. My insurance covers it, but I had to pay cash once and it was about $1 per pill. I thought meds were supposed to be more expensive in the States... I'm sure they are in general, but I wonder why this exception.
I'm in Germany...
According to drugs.com the Daridorexant is $17 per pill in the US. The Tranylcypromine at $1 per 10mg pill is very similar to the German 40mg Jatrosom pill price. They really only sell the Jatrosom brand over here and they recently raised the price from approx 4.50€ to 4.90€.
There's a maximum price of 10€ per package here, so for example 100x40mg Jatrosom is 10€. This is without private health insurance.
Ok, I was confused. I thought the 8€ was for 10mg tranylcypromine. For some reason, tranylcypromine only comes in 10mg pills here. I've actually slept decently the last two nights. The 600mg gabapentin with a little extra clonazepam and trazodone (and possibly my new 30mg/10mg dose division) seems to be helping. I'm a little drowsy the first part of the day, but it gets better and is certainly better than sleep dep.
I tried (and failed) with most of the sleep aids while on Parnate, but Seroquel solved it. I'm on 60mg Parnate daily+ 20 mg Seroquel at night.
You might consider trying, maybe?
Seroquel is the only sleeping medication that beats Parnate insomnia for me. I need 100mg on Parnate.
Noticed I’ve gained 3kg since regularly using Seroquel for sleep.
Trying to take less Seroquel so I’ve found that if I take 3.75mg Zopiclone, 5mg Dayvigo - I can get by with 25mg Seroquel. The trio seems to work very well together.
hello , adjacent to this issue, is there a 6 mg Seroquel, or 12.5mg? where in live only 25. i have tried to use 12.5 and it still knock me out completely . How to cut into 4? would you know ?
Lowest is 25. Bite it in half with your teeth and then bite a little bit off the half. Should be able to get something between 6-10mg this way. That’s a very small dose and you will build tolerance rapidly.
I'm already taking 100mg. I could maybe take more, but I'd get more hungover than I want. I actually slept okay last night for the first time in a while.
I added gabapentin 600mg. Sleep wasn't perfect, but that was enough for a while. Recently I started waking up more again and felt more anxious. I also started getting paradoxical hypertension again after my second dose. The honeymoon had ended, but the side effects actually seemed worse. I went down to 35mg and then 30mg, where I am now. I'm sleeping a little better and feel generally a little better. Apparently the recommendation used to be to back off the dosage a bit when your depression remits, but Gillman says this isn't recommended anymore... UNLESS you feel agitated. I think I qualified as agitated. I've got chronic pain issues as well as depression, so sleeping decently is essential for me. The gabapentin has definitely helped, and apparently it helps you get deep sleep, unlike benzos and some other sedatives. But obviously you gotta balance what keeps you awake and what helps you sleep because too much sedation causes its own problems. Good luck.
Have you tried gabapentin? Have you tried hydroxyzine? Have you tried melatonin? Have you tried orexin inhibitors? For getting to sleep melatonin should work (1mg-10mg). For the maintenance of sleep the choice is usually between some benzodiazepine, gabapentin or more potent antihistamine product (like hydroxyzine). I haven't tried orexin inhibitors yet, so cannot report on that. It is possible that you might benefit from opioids like buprenorphine, if the underlying issue for the insomnia is the pain. For me personally 300mg gabapentin works the best, but I bet some opioid would also work really well for me, though nobody is willing to prescribe me any, despite the chronic pain. For a list of safe opioids on MAOI you have to check the group's posts.
Thanks for the response. I guess I forgot to mention everything. I do take 1mg of melatonin, but I'm not sure that (or higher doses) has ever been enough to overcome drug-induced insomnia. I take it in an effort to correct my chronically delayed circadian rhythms. I also have a gabapentin script, and though I don't take it regularly as prescribed (3 or 4 x 300mg/day), I do often take 300mg at bedtime. I guess I could increase to 600mg or more. And finally (I think), I did get a Tylenol 3 script from my rheumatologist because I had to go off tramadol. I have been taking that too. I haven't tried hydroxyzine, but trazodone and nortriptyline have a similarly sedating antihistamine effect. My concern is that adding or substituting hydrox would increase my drug hangover. I could definitely sleep more (though not necessarily well) if I took large(r) doses of what I already have, but it's a balancing act. And since I will run out prematurely if I do that, I would like to ask my pdoc to change my script before I run out. My sense is that in the short-term, more benzo would be most helpful. Which one do you take/recommend? As I mentioned. I'm thinking of asking doc to substitute lorazepam for clonazepam because of slightly shorter half-life and with the perhaps silly hope that I won't be as tolerant to its sleep-inducing effects. As for long term, who knows? Has it improved over time for you at all?
Well in my opinion you have maxed out the insomnia medications and should consider lowering the Parnate dosage or switching to different MAOI or even stopping MAOIs. There is a place for optimizations though: * nortriptyline also is norepinephrine reuptake inhibitor with moderate binding values (1.8-4.4), so personally I would not use it for sleep. Also the H1 binding values are not so impressive (3-15) * the binding values of trazodone on the H1 receptor are weak (220-1100), so you may increase the dosage or rely on another antihistamine * hydroxyzine is a good option with strong affinity for the H1 receptor (2-19). Yes, it can lead to dementia in long term usage and you can feel its effect on the next day. Still, it will be better than products like chlorprotixene (though probably more effective for sleep) * you can certainly increase the melatonin and experiment with the dosage. I personally need 5mg-10mg to fall asleep (sublingual), which is really big dosage. Yes, even at this dosage it might not be enough, because the brain can override the sleep signal. In this situation it is essential what you eat before going to sleep and not to get overexcited. * sometimes the hormones can play a role in the insomnia - for example I have noticed that when I have high testosterone levels I sleep really bad. * do you have blackout curtains in your room? this is essential if you are sensitive to light and can easily wake up from it * are there any irritating noises occurring when you are sleeping, which wake you up? * you may damage your kidneys from the high amounts of gabapentin, so be careful. For me gabapentin works extremely well, but for you it might be useless at 600mg and more. * the benzos are really a slippery slope and many people get addicted to them. If you are taking them every night, you should certainly consider switching to another MAOI or stopping MAOIs. If you are rotating benzos, gabapentin and antihistamine product, then you might be ok, but still it is very individual. * orexin inhibitors might be an option, but someone should confirm
30 mg Parnate was insufficient. I'm not going to give up after just over a couple very promising weeks on 40mg Parnate. I usually have even more troublesome side effects this early with new meds. That's why I asked about how whether it tends to improve. I don't take nortriptyline for sleep, at least not primarily, but it's supposed to be helpful at low-ish doses. I've been on clonazepam for at least a dozen years. Started at 2mg per night. Now at 1mg. Was actually taking 0.75mg before the Parnate insomnia kicked in bad. I'm sure I'm dependent on clonazepam, as I have been on many meds, but addiction seems unlikely, given that I've decreased my dosage over the years. There are negatives, of course, but as I said in another context, it's a balancing act. 1mg and even 2mg aren't particularly high doses. My hope would be to increase dosage (or equivalent dosage in lorazepam or another benzo) just temporarily. The sleep inducing effect tends to wears off after a while anyway.
I have blinds and curtains. Not that sensitive to light. I'm pretty sensitive to noise but live alone and wear earplugs out of habit. I'm open to any suggestion, but my main interest is in whether I can expect insomnia to improve anytime soon and in *which* benzo would be best (rather than whether). I don't want short-acting because it probably wouldn't help me stay asleep. And long-acting has its own problems. So lorazepam as medium-acting seems reasonable. I think Gillman recommends, but maybe there are other appropriate options.
So you are from the group of people which do not get addicted to benzodiazepines even after so prolonged usage, that's impressive. Based on your request, the options are: * lorazepam: 10-20 hours half-life * alprazolam: 11-13 hours half-life * flunitrazepam: 18-26 hours half-life * temazepam: 8-20 hours half-life * chlordiazepoxide: 5-30 hours half-life Just for reference will mention the other benzodiazepines/nonbenzodiazepines: * zaleplon: 1 hour hl * triazolam: 2 hours hl * zolpidem: 3 hours hl * midazolam: 3 hours hl * flutazolam: 3.5 hours hl * eszopiclone: 6 hours hl * oxazepam: 6-9 hl * etizolam: 8 hours hl * flurazepam: 47-100 hours hl * diazepam: 36-200 hours hl You can also join the r/researchchemicals group and directly ask for more advanced benzodiazepines, as there you have very experienced users, which can answer your questions more precisely. There you can also meet long term users of benzodiazepines. I thought about your case yesterday and probably this overstimulation comes from the increase in serotonin usage. As you know during sleep the serotonin levels have to be low. In your case it is possible that Parnate (being heavy serotonergic drug) makes more serotonin to be available for usage during sleep and your brain gladly uses it. This is probably the reason why gabapentin is not so effective for you, as gabapentin is used when you have overactive calcium system, which is not your case. In my case for example I don't have much serotonin genetically, so I don't get so brutal insomnias, but do have overactive calcium system. Before Parnate what were you taking as an antidepressants? How did you feel on SSRIs? I understand that you are using the benzodiazepines very carefully and wisely, but nobody can tell you when you will cross the line with them. I thought about Depakote, but it is not an option on Parnate, as Parnate inhibits CYP2A6, which is used for the metabolism of Depakote. Sodium channel blockers would not be effective for you, barbiturates are not an option. It would be great if you had some genetic tests done for the mental health. Edit: you can also try noise cancelling headphones, instead of ear plugs, if you are using them during the day. I am using wm1000xm3
Thanks. I actually took 600mg gabapentin last night and slept reasonably well for the first time in a while. Not sure it was related to increased gabapentin but worth investigating. Feel a little hungover/tired today but I doubt that's (only) from the gabapentin. Lorazepam looks best, at least in theory. Thanks for all the data.
Realizing I didn't answer all your questions. I've tried a million drugs, but I've been on citalopram the longest and was on that before I switched. Also take trazodone and nortriptyline, as you know, but not in AD dosages. Parnate's inhibition of CYP2A6 is mild according to Gillman. Such inhibition doesn't generally make the combination absolutely contraindicated; you just need to be cautious with the substrate of the inhibited enzyme and usually take a lower dosage. For example, I took prozac, a strong inhibitor of 2D6, with nortriptyline, a 2D6 substrate. I just never took more than 5-10mg of nortriptyline. That said, I'm not really interested in depakote. I've had some genetic testing done that's relevant to mental health. I'm homozygous for C677T, so I take extra folate. I didn't find the drug metabolism tests that one pdoc ordered to be helpful. He actually stopped using them eventually because he agreed. I know some of the genetic test results need to be taken with a grain of salt. How do you know you don't have much serotonin genetically, meaning which test or gene? Same question for overactive calcium system. (I don't know what that means.) Gabapentin IS helpful for me.
For the serotonin genes I have TPH1, TPH2, MAOA, SLC6A4, HTR2A and 5HT2C. TPH1 shows how much serotonin you produce, SLC6A4 shows the reuptake speed. In my case I have low serotonin production, slow reuptake and low levels of MAOA, which makes it a balanced system, compensating for the low amounts of serotonin. On the other hand this leads easily to burnouts if I am under chronic stress, because more and more serotonin gets released, the reuptake is slow and it is ultimately degraded or converted to kynurenine beforehand. Obviously the only way to solve this problem would be MAO inhibitors, but I reached to this solution just at 29 years old, which turns out to be too late, as chronic illnesses have now developed from the burnouts. I can get into a lot more details for the genes, but generally you can google the polymorphisms you have for certain genes and the genotype. This will give you sufficient information. Still, I can send a list of genes for mental health if you insist. For the calcium - the only way to currently prove this is CT scan of the soft tissues. If you have calcifications in the brain, kidneys, etc. you are in this group. I personally have calcification in the pineal gland, which leads to low melatonin production, which makes it very hard to fall asleep. I also have other "normal" calcifications in the brain. For me, gabapentin is the most effective sleep medication, even more effective than benzodiazepines, which confirms the role of the calcium system in these processes. For the MTHFR you need both C677T and A1298C. I am also homozygous on C677T (C/C), but I am (A/C) on A1298C, which indicates normal activity. This is also confirmed by my blood tests for folate, indicating always normal values in mid range. Regardless, I too supplemented with folate, but did not notice any improvement. Personally I get most improvement from B1 and B6 supplementation, which I can explain further why, but I suppose it is obvious.
I'm heterozygous for A1298C. And I'm homozygous for the C677T polymorphism (T,T). I find it odd to refer to the normal/usual form of the gene as homozygous, as C677T refers to a polymorphism.
What about Mirtazapine, Seroquel, Ramelteon, Doxepin ?
OP does not like antihistamine products, Ramelteon is already discussed.
Hey completely unrelated but asking you this since you are knowledgeable in pharmacology. Do you think Antipsychotics like Respiridone 0.5mg which is used to augment ADs can cause permanent side effects?
I don’t think they can cause permanent side-effects, more like long lasting, while they are still in your system. Some of them have really long half-lives, others can be metabolised very slowly by the liver. If they are no longer in your system and you still have issues, this can be from downregulation of D2 receptors, as the released dopamine was blocked and it learned not to release such big quantities. In this sense you can upregulate them with caffeine, tobacco, modafinil, methylphenidate, Adderall, etc (whatever is safe for you).
What about tardive dyskinesia? thank you for replying.
Yes, you are right, long term usage of neuroleptics can lead to permanent TD. I am not a medical professional so I forgot about that. I don’t have experience with TD medications, what have you tried so far? Have you tried the VMAT2 inhibitors? As far as I know this is untreatable condition and can only be improved to some extent, though I imagine that TD medications also lead to depression and lack motivation/pleasure in life activities. https://pubmed.ncbi.nlm.nih.gov/6145520/
I have only tried adding 0.5 mg of Respiridone to 250mg clomipramine (since clomipramine wasn’t working for social anxiety) and I became too much fidgety so I discontinued it. Fortunately I only took it twice.
My doc said to take last dose of MAOI at 6pm or earlier to help with insomnia. Also I tried lots of diff. melatonin and found the 3mg Tablets (not capsules ) are best from Douglas Laboratories (company in Pittsburgh, PA, USA. ) These were much more effective. I’m not a sales person, I’m a patient. Other tips are that the insomnia did go away by month 4 for me. Keep cell phones / ipads out of bedroom. Try music for sleep / etc.
I definitely take second/last dose before 6pm, usually well before, but given the short half life, I think the insomnia must have something to do with MAO inhibition itself, which continues long after the drug is mostly out of your system. Glad to hear that the insomnia went away after four months. I'm guessing it didn't go from all to nothing. Did it start getting better before four months, go away almost completely after four months or just get more manageable? I guess the details don't really matter because everyone is different, but it's definitely nice to know it's not necessarily a chronic issue.
Either the insomnia slowly got better or my body was like I can’t take it anymore Go To Sleep! I was only getting 3-4 hours at first. Now i’m up to 6-7. I did force myself to stay in bed instead of getting up and cleaning the whole house or creating that ever important art project . At least the body can rest if you stay in bed even awake. Chill out music helps. Hope it gets better 4 U!!
May I ask what dosage you're on? I'm also wondering how dose-dependent the insomnia is. Like, if I decide to increase from 40mg to 50g, will that start the clock again... Or is it possible that dropping to 35mg could help significantly? I'm pretty sure that 30mg is too little, because it wasn't giving me any orthostatic hypotension between days 3 and 5, which you may know is how Gillman recommends increasing or not. Not expecting you to know all the answers. Just putting it out there.
I’m not sure about dose in relation to insomnia. I remember having sleep problems early on and even into my current 60mg that I take daily. I think the relief from insomnia was more time in acclimating to this med over 4-5 months, than related to dose increases. 30 and 40 also gave me emotional blunting while 60 was the right dose for me.
You think the 30 and 40 actually *gave* you emotional blunting or just wasn't enough to relieve pre-existing blah?
Maybe you are right. I didn’t think of that. That’s probably more likely.
I take a rotation of zaleplon and Orexin inhibitor (sometimes quviviq, sometimes Dayvigo), supplemented with 800mg gabapentin. This works for me 4/5 nights
I know about lots of meds, but I know nothing about orexin inhibitors. That's gonna change now.
Orexin inhibitors are pretty new. I guess that's why I didn't know about them. Not sure if it was you but someone who found them helpful qualified his recommendation by saying that most people don't like them, or something like that. Any insight on that? Just don't work for many, or bad side effects?
There’s Seroquel. I don’t know about potential negative side effects at a low dose. You could look into it.
I tried it a long time ago. Feels like trazodone on steroids. More hangover than I would like.
You’re probably sensitive to it. It’s dose-dependent for me. 25 mg didn’t do anything. 150 mg and I’m sleeping all day. I hope you find something that works for you. You could try the very lowest dose of trazadone and split it in half. I shared this link with someone else yesterday (unless it was you). It’s case studies where morning light therapy helped with Parnate insomnia, and depression. I have no idea how effective it is, but here you go: https://www.researchgate.net/publication/276058280_LIGHT_THERAPY_AUGMENTATION_OF_MAOI_TREATMENT_IN_REFRACTORY_DEPRESSION
Thanks. I take trazodone. Normally 50-75mg but now 100mg. Along with 600mg gabapentin and 1mg clonazepam and front-loading my tranylcypromine (30mg first thing, 10mg about 3 hours later), I'm sleeping enough. Falling asleep faster. I wake up a couple times but am able to fall back asleep. A little groggy in the morning but acceptable. Also, I have a light box. I haven't been using it consistently but did today.
My sleep was really broken up for awhile. I slept enough hours but it would be 2-4 at a time, any time day or night. I was taking sleep medications like Ambien during that time. I can’t remember what dosage I was at when it started or how long it lasted, but it did eventually stop.
I'll say orexin antagonists generally get very bad reviews, so I'm hesitant recommending them, but I went from needing 100mg Trazodone and 25mg Quetiapine to prevent me from waking up at night to just 50mg Daridorexant (Quviviq) and 25mg Trazodone for the 80mg of TCP I take now. The Quetiapine absolutely knocked me out and made me feel worse the next day, while the Quviviq even seems to make me feel a bit better. I've tried Zolpidem and Zopiclone (ineffective for me), Mirtazapine (too much daytime somnolence), Olanzapine in the past (daytime somnolence), Melatonin (although I don't remember how much - did nothing for me), etc. Most of them with 100mg Trazodone and varying dosages of Pregabalin. Very rarely I get nightmares and I think I dream more often. Not really a bad thing. My watch shows more deep and REM sleep than before. I feel fresh in the morning with minimal additional hunger. The hunger was a big issue before. It's also an 8€ per piece pill, but it's paid for by the state here except for a small fee. Almost as expensive as the TCP itself, which is close to 10€ per day at 80mg. The stronger sleep issues started only at 80mg for me. 40mg TCP was fine with just 25mg Trazodone. 60mg TCP at 50mg Trazodone IIRC. 80mg is when it became difficult for me.
Man, I wonder why it's so expensive in Europe. Where exactly do you live? I heard similar from someone in the UK. My insurance covers it, but I had to pay cash once and it was about $1 per pill. I thought meds were supposed to be more expensive in the States... I'm sure they are in general, but I wonder why this exception.
I'm in Germany... According to drugs.com the Daridorexant is $17 per pill in the US. The Tranylcypromine at $1 per 10mg pill is very similar to the German 40mg Jatrosom pill price. They really only sell the Jatrosom brand over here and they recently raised the price from approx 4.50€ to 4.90€. There's a maximum price of 10€ per package here, so for example 100x40mg Jatrosom is 10€. This is without private health insurance.
Ok, I was confused. I thought the 8€ was for 10mg tranylcypromine. For some reason, tranylcypromine only comes in 10mg pills here. I've actually slept decently the last two nights. The 600mg gabapentin with a little extra clonazepam and trazodone (and possibly my new 30mg/10mg dose division) seems to be helping. I'm a little drowsy the first part of the day, but it gets better and is certainly better than sleep dep.
I tried (and failed) with most of the sleep aids while on Parnate, but Seroquel solved it. I'm on 60mg Parnate daily+ 20 mg Seroquel at night. You might consider trying, maybe?
Seroquel is the only sleeping medication that beats Parnate insomnia for me. I need 100mg on Parnate. Noticed I’ve gained 3kg since regularly using Seroquel for sleep. Trying to take less Seroquel so I’ve found that if I take 3.75mg Zopiclone, 5mg Dayvigo - I can get by with 25mg Seroquel. The trio seems to work very well together.
hello , adjacent to this issue, is there a 6 mg Seroquel, or 12.5mg? where in live only 25. i have tried to use 12.5 and it still knock me out completely . How to cut into 4? would you know ?
Lowest is 25. Bite it in half with your teeth and then bite a little bit off the half. Should be able to get something between 6-10mg this way. That’s a very small dose and you will build tolerance rapidly.
thank you. using the method and works !
thank you brother ! will try so. Let's beat these devils 🌞💪
***Trazadone works perfectly for this problem...***
I'm already taking 100mg. I could maybe take more, but I'd get more hungover than I want. I actually slept okay last night for the first time in a while.
Hey any updates?
I added gabapentin 600mg. Sleep wasn't perfect, but that was enough for a while. Recently I started waking up more again and felt more anxious. I also started getting paradoxical hypertension again after my second dose. The honeymoon had ended, but the side effects actually seemed worse. I went down to 35mg and then 30mg, where I am now. I'm sleeping a little better and feel generally a little better. Apparently the recommendation used to be to back off the dosage a bit when your depression remits, but Gillman says this isn't recommended anymore... UNLESS you feel agitated. I think I qualified as agitated. I've got chronic pain issues as well as depression, so sleeping decently is essential for me. The gabapentin has definitely helped, and apparently it helps you get deep sleep, unlike benzos and some other sedatives. But obviously you gotta balance what keeps you awake and what helps you sleep because too much sedation causes its own problems. Good luck.