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Alternative To Xyrem Possibly?


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#1 Garch2010

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Posted 10 January 2012 - 02:47 PM

I am going to ask to try Agomelatine as it seems to have a similar action to Xyrem but is very much less expensive. See below. Anyone tried this?


BACKGROUND: Disturbance of sleep-wake cycles is common in major depressive disorder (MDD), usually as insomnia, but also as hypersomnia or reduced daytime alertness. Agomelatine, an MT(1) and MT(2) receptor agonist and 5-HT(2C) receptor antagonist, represents a novel approach in MDD, with proven antidepressant efficacy and a positive impact on the sleep-wake cycle. We review the effects of agomelatine 25/50 mg/day on objective and subjective measures of the sleep-wake cycle in MDD. SUBJECTIVE MEASURES: Agomelatine improved all aspects of the sleep-wake cycle from as early as 1 week in randomized trials versus selective serotonin reuptake inhibitors and venlafaxine, particularly getting off to sleep and quality of sleep, with an improvement in daytime alertness. OBJECTIVE MEASURES: Agomelatine's effect on sleep architecture in MDD has been measured by polysomnography (PSG). There were significant improvements in sleep efficiency, slow-wave sleep (SWS), and the distribution of delta activity throughout the night, but no change in amount or latency of rapid eye movement (REM) sleep. Furthermore, the slow-wave sleep was resynchronized to the first sleep cycle of the night. CONCLUSION: Agomelatine, a novel antidepressant, improves disturbed sleep-wake cycles in MDD. The improvement of both nighttime sleep and daytime functioning with agomelatine are promising features of this antidepressant regarding the management of MDD.

#2 petitelinguiste

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Posted 12 January 2012 - 12:34 PM

I'm certainly not a chemist/pharmacist/doctor... but I saw this on Wikipedia:


Agomelatine does not alter daytime vigilance and memory in healthy volunteers. In depressed patients, treatment with the drug increased slow wave sleep without modification of REM (Rapid Eye Movement) sleep amount or REM latency. Agomelatine also induced an advance of the time of sleep onset and of minimum heart rate. From the first week of treatment, onset of sleep and the quality of sleep were significantly improved without daytime clumsiness as assessed by patients.[2]


While it says it increased slow wave sleep, it also says it did not modify REM. The vast majority of challenges we face with N are related to REM sleep. We go into parts of it at the wrong time, we enter it too fast, it makes up too much of our overall nighttime sleep, etc... so if the medication wouldn't change that, I wonder if it would just shorten any periods of time we might spend in stages 1 and 2 of sleep? Especially since many of us nosedive right into stage 3 when we're not immediately going into REM.

Now, that's only my guess. I really have no idea one way or the other...

#3 SoSickness

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Posted 15 January 2012 - 11:26 PM

I'm guessing nobody here has tried this as a treatment for narcolepsy. If its not approved to treat narcolepsy, it presumably won't treat narcolepsy. If you're still curious about it, go ahead and ask your doctor.

#4 Garch2010

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Posted 16 January 2012 - 03:11 PM

Hi,

It's not approved for Narcolepsy. Not surprising as it a very very new drug. Mr Dr has prescribed me a month supply and I'm on day 2. He says I'm a human Ginnie Pig! It takes about 2 - 3 weeks to reach therapeutic potential so will have to wait and see. I've got the home single channel EEG Zeo so will monitor carefully the sleep architecture. My cataplexy is quite infrequent, a few times a year so REM suppression is not so critical to me. I'm more interested in the Stage 3/4 SWS benefits as that hopefully will reduce the excessive day time sleepiness. In addition it is also a mood brightener, so nice side effects (increases mood, libido, drive and motivation). There are some reports that off-label use to treat some types of hypocretin deficient idiopathic hypersomnias have been positive.

So far no nasty side effects at all. Quite remarkable for an "antidepressant" class drug. Well not strictly true, my libido has rocketed up when I wake in the morning (I'm a 43 year old male). To suppress REM I would probably just add a small dose of a short half-life SSRI first thing in the morning. I take 25mg of Agomelatine just before bed, as instructed.

#5 N50+

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Posted 05 February 2012 - 12:36 PM

"and I'm on day 2. He says I'm a human Ginnie Pig! It takes about 2 - 3 weeks to reach therapeutic potential so will have to wait and see."

Looks like its been about 2 weeks, care to report any results so far?

#6 Maximilian

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Posted 15 October 2012 - 05:25 AM

*bump*

#7 DeathRabbit

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Posted 15 October 2012 - 09:25 AM

*bump*


I had an interesting thought the other day. I wonder if narcolepsy causes decreases in amounts of GABA (GABA wiki). It might go a long ways to explaining why Xyrem aka GHB helps us, since it has an identical chemical structure to GABA, only difference is the H2N kicker on the left instead of the OH. And GHB does have a receptor affinity for GABA( b ) receptor. I'm wondering about getting some supplements with GABA in it. I've seen it sleep aids and OTC mental stimulants, so if I try it I'll let you guys know.

#8 Megssosleepy

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Posted 15 October 2012 - 01:29 PM

I had an interesting thought the other day. I wonder if narcolepsy causes decreases in a mounts of GABA (GABA wiki). It might go a long ways to explaining why Xyrem aka GHB helps us, since it has an identical chemical structure to GABA, only difference is the H2N kicker on the left instead of the OH. And GHB does have a receptor affinity for GABA(B) receptor. I'm wondering about getting some supplements with GABA in it. I've seen it sleep aids and OTC mental stimulants, so if I try it I'll let you guys know.


Wonder what happened to this guy... I am liking the sound of the 2 day and he already feels a bit better? Is there any new studies on the treatment! I am finding that being off the Prozac my anxiety has increased... but all the other side effects of taking it along with the Xyrem and Adderall are going away slowly (as it tapers out of my system) I would love to be a human ginnie pig... as long as this guy survived it!!

#9 tdmom

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Posted 19 October 2012 - 11:17 PM

I'm guessing nobody here has tried this as a treatment for narcolepsy. If its not approved to treat narcolepsy, it presumably won't treat narcolepsy. If you're still curious about it, go ahead and ask your doctor.


When a drug is not approved to treat something, such as Agomelatine and narcolepsy it doesn't mean it won't treat Narcolepsy but that no studies were done with this drug as a treatment for Narcolepsy. Sometimes what happens is a drug is approved as a treatment for one disease process. People and Doctors notice certain symptoms are improved for coexisting processes. Then either a study is done and approval sought for that drug to be a treatment with dosages suggested for that disease process, or Dr.'s just start prescribing it for people with the other disease process.

#10 Garch2010

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Posted 22 October 2012 - 02:27 AM

Wonder what happened to this guy... I am liking the sound of the 2 day and he already feels a bit better? Is there any new studies on the treatment! I am finding that being off the Prozac my anxiety has increased... but all the other side effects of taking it along with the Xyrem and Adderall are going away slowly (as it tapers out of my system) I would love to be a human ginnie pig... as long as this guy survived it!!



Hi, I did try the Agomelatine for 3 months. But always made me feel a bit slow and sluggish the next day.
I eventually settled on Mirtazapine 15mg/d and have been on it for 9 months. It definitely boosts slow wave sleep and consolidates sleep at night very well indeed.

I've tried SSRIs and I don't react to these at all well. Also tried tricyclics but didn't like the side effects.

#11 DeathRabbit

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Posted 22 October 2012 - 12:16 PM

Hi, I did try the Agomelatine for 3 months. But always made me feel a bit slow and sluggish the next day.
I eventually settled on Mirtazapine 15mg/d and have been on it for 9 months. It definitely boosts slow wave sleep and consolidates sleep at night very well indeed.

I've tried SSRIs and I don't react to these at all well. Also tried tricyclics but didn't like the side effects.

That's odd. Everything I've heard about Remeron said it either leaves REM alone or increases it. My roommate is on it and it causes all sorts of sleep paralysis and the like and his docs are wanting to take him off of it now, because they say it's increasing his REM

#12 DeathRabbit

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Posted 22 October 2012 - 12:19 PM

Okay, according to this it increases SWS and REM. Clicky

Interesting. I don't want to risk it though. I'm currently cataplexy free, despite having REM like stuff in my wakeful time, so I don't wanna chance it.

#13 Garch2010

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Posted 22 October 2012 - 12:44 PM

Okay, according to this it increases SWS and REM. Clicky

Interesting. I don't want to risk it though. I'm currently cataplexy free, despite having REM like stuff in my wakeful time, so I don't wanna chance it.


I know it has left my duration of REM largely unchanged. I have a home EEG I wear at night. SWS up a lot ( as would be the case with Xyrem ) and sleep continuity much much better.
REM onset from less than a minute within Stage 1 sleep to over an hour through each stage as it should be. Also no more sleep paralysis, sleep stage 1 hallucinations etc.

#14 Garch2010

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Posted 23 October 2012 - 02:21 AM

http://www.ncbi.nlm....ubmed/16491981/

RESULTS: Mirtazapine administration increased total SWS and the SWS in the first sleep cycle, but not SWS in the second sleep cycle. The medication increased REM latency and the duration of the first REM episode; it also decreased the number of REM episodes. Simultaneously, mirtazapine significantly reduced wake-after-sleep onset and scores on the Athens Insomnia Scale

#15 Megssosleepy

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Posted 23 October 2012 - 01:52 PM

Xyrem forces the brain into SWS where I get none on my own. So does Mirtazapine create SWS or just increase it in people who are able to reach deep sleep?

#16 Garch2010

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Posted 23 October 2012 - 04:23 PM

Xyrem forces the brain into SWS where I get none on my own. So does Mirtazapine create SWS or just increase it in people who are able to reach deep sleep?


Very good question. I haven't seen any studies with Remeron and subjects with zero SWS. Use in Narcolepsy is so off-label that I'm sure nobody knows an answer to that.

But over several months it took my SWS from 1pct of SWS to 10pct, which is almost from zero to normal.

What I like about Remeron is that it does not blindly inhibit REM sleep, but rather it delays REM onset back to where it should be and normalises REM back into sleep architecture that looks more like "typical controls".

It also boosted my libido which was one reason why I shunned SSRIs and Tricyclics.

#17 Garch2010

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Posted 23 October 2012 - 04:55 PM

I had an interesting thought the other day. I wonder if narcolepsy causes decreases in amounts of GABA (GABA wiki). It might go a long ways to explaining why Xyrem aka GHB helps us, since it has an identical chemical structure to GABA, only difference is the H2N kicker on the left instead of the OH. And GHB does have a receptor affinity for GABA( b ) receptor. I'm wondering about getting some supplements with GABA in it. I've seen it sleep aids and OTC mental stimulants, so if I try it I'll let you guys know.


Not sure if GABA supplements will really do the trick.

Sodium Oxybate has the paradoxical mix of sedative and stimulatory properties as it simultaneously acts on on GABA B and GHB receptors in the brain. GABA B being inhibitory and GHB receptors being excitory. The structure of the GABA class of receptors are notoriously complex and inhibit in both linear and non linear ways, actually much like a shock absorber in your motor vehicle - small bumps in the road elicit a near linear response from the shocks, a huge bump eliciting a non linear response from the shocks.

#18 Hank

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Posted 23 October 2012 - 06:22 PM

Not sure if GABA supplements will really do the trick.

Sodium Oxybate has the paradoxical mix of sedative and stimulatory properties as it simultaneously acts on on GABA B and GHB receptors in the brain. GABA B being inhibitory and GHB receptors being excitory. The structure of the GABA class of receptors are notoriously complex and inhibit in both linear and non linear ways, actually much like a shock absorber in your motor vehicle - small bumps in the road elicit a near linear response from the shocks, a huge bump eliciting a non linear response from the shocks.



This is really interesting to me. I was previously misdiagnosed with a REM disorder and treated with a Benzodiazapine. Unfortunately, I actually had Narcolepsy. While the Benzo decreased REM and kept me still at night, it treated my EDS with sedation and turned bad into worse. In order to be correctly diagnosed, I had to go through Benzo withdrawal- aka "Hell". The end result of that is sluggish GABA receptors for months. I have been on Xyrem since July and my GABA receptors have been recovering since March. This has added layers of complication to my treatment and my life in general, as I try to manage my responsibilities at home and work.

My nights on Xyrem have been a roller coaster and I wake up frequently, even on 4.5 x 2. Much of this I attribute to recovery from Benzo withdrawal. I do feel better than ever during the day, since starting Xyrem- but my sleep at night is chaotic and I wake up often. I have been doing my homework and what you have said fits with what I have read.

If my GABA receptors are still recovering, and the inhibatory effect is lessened by my sluggish GABA receptors, then the ecxitatory effect from the GHB receptors would be more pronounced. And, as my GABA receptors continue to recover, I should expect continued improvement on Xyrem. So, to make a leap with this thought, I can use the quality of my sleep as a reference point for the recovery of my GABA receptors.

You made points on GABA inhibiting in linear and non linear way- that is something new to me. Can you add some more about that. I will start my homework on that because I am really trying to understand that. I have not been myself for the past year and understanding all of this helps me a lot. Thank you.

#19 Garch2010

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Posted 24 October 2012 - 03:35 AM

This is really interesting to me. I was previously misdiagnosed with a REM disorder and treated with a Benzodiazapine. Unfortunately, I actually had Narcolepsy. While the Benzo decreased REM and kept me still at night, it treated my EDS with sedation and turned bad into worse. In order to be correctly diagnosed, I had to go through Benzo withdrawal- aka "Hell". The end result of that is sluggish GABA receptors for months. I have been on Xyrem since July and my GABA receptors have been recovering since March. This has added layers of complication to my treatment and my life in general, as I try to manage my responsibilities at home and work.

My nights on Xyrem have been a roller coaster and I wake up frequently, even on 4.5 x 2. Much of this I attribute to recovery from Benzo withdrawal. I do feel better than ever during the day, since starting Xyrem- but my sleep at night is chaotic and I wake up often. I have been doing my homework and what you have said fits with what I have read.

If my GABA receptors are still recovering, and the inhibatory effect is lessened by my sluggish GABA receptors, then the ecxitatory effect from the GHB receptors would be more pronounced. And, as my GABA receptors continue to recover, I should expect continued improvement on Xyrem. So, to make a leap with this thought, I can use the quality of my sleep as a reference point for the recovery of my GABA receptors.

You made points on GABA inhibiting in linear and non linear way- that is something new to me. Can you add some more about that. I will start my homework on that because I am really trying to understand that. I have not been myself for the past year and understanding all of this helps me a lot. Thank you.



The downside of the hypnotic properties of benzodiazepines is that they actually worsen the sleep architecture and thus the quality of sleep.

Certain substances, such as benzodiazepines (e.g. Ativan, Valium, Klonopin) seem to have a reverse effect on the time spent in SWS. Instead of lengthening SWS, they are known to shorten the time. While these sedatives can increase sleep duration or shorten the time it takes before sleep-onset occurs, they tend to deprive patients of deep sleep.

A decrease in SWS can lead to reduced REM latency and a increase in REM period durations - in other words worsening of Cataplexy.

#20 Hank

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Posted 24 October 2012 - 07:41 AM

The downside of the hypnotic properties of benzodiazepines is that they actually worsen the sleep architecture and thus the quality of sleep. Certain substances, such as benzodiazepines (e.g. Ativan, Valium, Klonopin) seem to have a reverse effect on the time spent in SWS. Instead of lengthening SWS, they are known to shorten the time. While these sedatives can increase sleep duration or shorten the time it takes before sleep-onset occurs, they tend to deprive patients of deep sleep. A decrease in SWS can lead to reduced REM latency and a increase in REM period durations - in other words worsening of Cataplexy.

Bingo. And, Benzo Withdrawal Syndrome, which I experienced full force, causes a REM rebound. My dreams were vivid and frequent and I would tell myself to wake up while in a dream. I was also able to do a lot of problem solving about this during my dreams through lucid dreaming. This also caused a worsening of Cataplexy to a level I had never experienced. Even with Xyrem, my Cataplexy, while it is lessening, is still more frequent and severe than I had ever experienced before Benzo Withdrawal. I had lived with mild Cataplexy for most of my life and could never identify it. I had falls that I could not explain, mostly when skiing and doing other sports. Fortunately, this experience with enhanced symptoms made my diagnosis more clear cut. Sleep Paralysis was also more frequent and severe. The changes Klonopin caused to my sleep architecture invalidated my sleep studies and delayed my correct diagnosis. Thankfully, my Sleep Doc knew this and started me through a 6 month slow-taper off Klonopin, which was still way too fast. In the end, I have survived it. It is amazing to me that physicians are so quick to start patients on these medications without considering an exit strategy. Thanks for you comments. I feel like a real life "show and tell" for the importance of drug interactions. My bottom line is that I will never take a medication without thorough doing my homework and getting a second opinion.