Warnings about Belsomra

Just some warnings that Belsomra (Suvorexant) may not be as safe as its trials claim it is, especially for people like us who are/were dependent on benzos. I think I am the first person on the internet who has had dependency and withdrawal issues with Belsomra; I thought I would be able to taper off in a little more than a month, but I think it's going to take much longer than that...

Suvorexant, a Dual Orexin Receptor Antagonist, Protected Seizure through Interaction with GABA A and Glutamate Receptors

https://pubmed.ncbi.nlm.nih.gov/33224245/

"Moreover, the protein levels of NMDAR and AMPAR were decreased by suvorexant. Suvorexant exerted anticonvulsant activity and in addition to its inhibitory effect on orexin receptors, this effect may be mediated, at least partly, through interaction with GABAA and glutamate receptors."

I don't think any of the trials for Belsomra mentioned anything about GABA A receptors.

In addition, I just noticed this in the medical uses section in the wikipedia entry for Belsomra (https://en.wikipedia.org/wiki/Suvorexant#Medical_uses):

"It is also unclear if this medication is safe among people with a history of addiction, as they were excluded from the clinical trials of suvorexant."

Which is not to say that people in the group are addicted--most of are/were physically dependent on benzos--but it sounds like the drug manufacturer went out of their way to avoid trials on people whose central nervous systems may not be optimal.

Don't be afraid of "Partially interacting with GABA A" claims.

Melatonin, for example, is a hormone that your brain produces in response to darkness. It helps with the timing of your circadian rhythms (24-hour internal clock) and with sleep. Being exposed to light at night can block melatonin production.

https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know

Picrotoxin:

Picrotoxin is widely regarded as a (GABA) pore-blocking agent that acts at the cytoplasmic end of the channel. However, there are also data to suggest that there may be an additional, secondary binding site for picrotoxin...we show that binding of picrotoxin to this interface pocket correlates with these data, and negative modulation occurs at the pocket via a kinking of the pore-lining helices into a more closed orientation.

https://pubmed.ncbi.nlm.nih.gov/24028067/

Picrotoxin's effect on Melatonin:

Neither doses of melatonin exerted significant effects on brain temperature, sleep architecture or sleep electroencephalogram (EEG). Moreover, melatonin failed to attenuate the picrotoxin-induced promotion of wakefulness. These observations indicate that melatonin hardly influences sleep-wake behaviour in rats.

https://pubmed.ncbi.nlm.nih.gov/11696074/

These results indicate that the hypnotic activity of melatonin may be linked to the GABA(A) receptor and mediated through the BZP recognition site, the picrotoxin site on the GABA(A) receptor and partially through the GABA binding site on the GABA(A) receptor.

https://pubmed.ncbi.nlm.nih.gov/12543221/

Buuuuuuuut!

Flumazenil:

Flumazenil is a benzodiazepine antagonist. It competitively inhibits the activity of benzodiazepine and non-benzodiazepine substances that interact with benzodiazepine receptors site on the GABA/benzodiazepine receptor complex. It can also reverse the binding of benzodiazepines to benzodiazepine receptors.

https://www.ncbi.nlm.nih.gov/books/NBK470180/

Flumazenil's effect on Melatonin:

Polysomnographic recordings and core body temperature recordings revealed that melatonin, either in combination with placebo or with flumazenil, significantly increased the amounts of sleep, and decreased core body temperature in comparison with placebo alone or the combination of flumazenil plus placebo. These results do not support the hypothesis that melatonin exerts its hypothermic and hypnotic effects via the central benzodiazepine receptors.

https://pubmed.ncbi.nlm.nih.gov/8878099/

Translation: 2 conflicting studies whether Melatonin directly affects GABA Receptors. The 2nd study that believes Melatonin does NOT affect The benzo site on the receptor sounds more concrete.

My take: Melatonin is strictly a hormone that binds to Melatonin receptors, not GABA receptors. BUT stimulating the Melatonin receptor is likely to create a natural, secondary reaction of endogenous hormones that DO activate GABA receptors. So it's not the Melatonin doing it, rather, the Melatonin is simply creating a domino effect.

I believe the same thing for Belsomra. The sad fact is that anything you use for sleep will get the brain used to needing that, and in essence, dependent on it. On another thread, I posted about my experiences with a machine that helps to make you sleep by cooling your forehead. It's completely drug free, and it broke on me yesterday. I had a sleepless night last night. My body was used to needing that cooling sensation to sleep.

It's likely you are dependent on Belsomra since you used it for so long. I don't blame you. I've been using Remeron for sleep, and Cannabis, both which bring their one dependence issues. I don't think either one, at the doses I'm using, will be "too" hard to break free from (maybe a few sleepless days, instead of months like a Benzo).

The problem with the Benzo is that it attacks exactly the receptors we need to sleep. I believe if your GABA receptors are shot, NOTHING will make you sleep, until they repair. This is why in acute, a lot of us go for days with zero sleep hours. But I don't believe Belsomra is one of those drugs.

I believe the same thing for Belsomra. The sad fact is that anything you use for sleep will get the brain used to needing that, and in essence, dependent on it. On another thread, I posted about my experiences with a machine that helps to make you sleep by cooling your forehead. It's completely drug free, and it broke on me yesterday. I had a sleepless night last night. My body was used to needing that cooling sensation to sleep.

 

It's likely you are dependent on Belsomra since you used it for so long. I don't blame you. I've been using Remeron for sleep, and Cannabis, both which bring their one dependence issues. I don't think either one, at the doses I'm using, will be "too" hard to break free from (maybe a few sleepless days, instead of months like a Benzo).

 

The problem with the Benzo is that it attacks exactly the receptors we need to sleep. I believe if your GABA receptors are shot, NOTHING will make you sleep, until they repair. This is why in acute, a lot of us go for days with zero sleep hours. But I don't believe Belsomra is one of those drugs.

But that's the issue (at least with me): my body did not revert to what my sleeping pattern was before taking the Belsomra--when I stopped, I went into withdrawal: akathisia, POTS, fear, restlessness, earworms--things I haven't experienced since the beginning of my second taper, which ended over 5 years ago. What's causing the withdrawal if all the trials showed that people did not develop dependence and did not go into withdrawal after abrupt discontinuation, even after taking Belsomra daily for a year?

Also, on a side note: do you think it takes years for GABA A receptors to repair? Or could it be that the glutamatergic receptors are too upregulated, in which case it would take a very long time to return to a pre-upregulated state (if ever)? For example, in my scenario, until the Belsomra/melatonin setback, I had no problems falling asleep: I could fall asleep anywhere, anytime in less than 15 minutes. My only issue--again, until the setback--was that I slept lightly and could sleep only a maximum of 1.5 hours before waking up. This has been a rigid pattern since my second taper ended; the only thing that varied was the amount of time it would take me to get back to sleep after waking up (a minute if things were going well, up to several hours if they were not - this happened for seven months after drinking lemongrass juice for just a few days).

My doctor gave me this a few weeks ago and I finally got around to trying it last weekend. I took half a 20mg pill and about 45 minutes later I started getting sleepy. Slept for 6 1/2 hours straight, woke up and used the bathroom and fell back asleep like 30 minutes later and slept another 2 hours. Then I tossed and turned for another 2 hours. I was still experiencing somnolence for a number of hours.

It seemed to be heart rate neutral and it didn’t seem to ramp my anxiety up too terribly. I slept without it the following night but since that night my sleep has been a mess again.

It isn’t something I’ll take often but I’ll consider it on those really bad nights. Used as needed it should be okay.