Posted by SLS on October 20, 2011, at 4:32:53
In reply to chronic unremitting insomnia - I can't take it!!!, posted by linkadge on October 19, 2011, at 17:46:36
> I don't know what to do. I am completely helpless and hopeless.
>
> I can't get more than about 3 hours of sleep a night. This is with some of the best sleeping medications.
>
> I feel like am going to accidently end up like Michael Jackson.
How much trouble do you have falling asleep (initiation)?
How much trouble do you have staying asleep (maintenance)?When do you fall asleep?
When do you awaken?How are your levels of depression and anxiety upon awakening?
Out of curiosity, how does one night's total sleep deprivation affect you the next day? Do receive an antidepressant effect? Do you sleep well the following night?
My sleep is pretty screwed up because I allow myself to fall asleep at 7:30 and awake three hours later, only to sleep sporadically for the remainder of the night. I can't seem to get past the overwhelming sleepiness that hits me at that time. When I do manage to remain awake until 10:00pm and promptly go to sleep, I do sleep better.
Did amitriptyline and nortriptyline help?
What does your sleep-wake pattern look like?
Maybe you can use Seroquel 25-50mg every few nights in an attempt to entrain the brain to sleep more regularly.
Which drugs make your insomnia worse? Does this occur with SSRIs?
Trimipramine might be useful as a sedative and help to improve sleep architecture. I don't know if this change in architecture would translate to an improvement in your sleep pattern. Being devoid of monoamine reuptake inhibition, this probably reduces the likelihood that Trimipramine will disturb sleep.
- Xyrem?
- Agomelatine?
- Ritanserin? (Used only experimentally)
Ritanserin specifically increases slow-wave sleep and decreases REM sleep.
HOMEWORK: Evaluate the pharmacology of Ritanserin. Design a drug cocktail containing the mechanisms displayed by this drug. 5-HT2a/b/c receptor antagonism. Actually, 5-HT2b antagonism serves to promote wakefullness and motor activity while its agonism helps to initiate sleep. It would probably be ideal to have a drug that acts as 5-HT2a/c antagonist + 5-HT2b agonist. Low dose Remeron combined with zaleplon would be an interesting combination. The zaleplon would help compensate for the lack of 5-HT2b agonism and enhance sleep initiation. Or perhaps allowing 5-HT to occupy this receptor is agonist enough to serve this purpose. Varying the ratios in the activity and manipulation of receptor subtypes might be important.
http://www.ncbi.nlm.nih.gov/pubmed/15265808
http://www.ncbi.nlm.nih.gov/pubmed/21459634
Ritanserin and insomnia:
http://www.ncbi.nlm.nih.gov/pubmed?term=ritanserin%20insomnia
Can you think of any clues that might help identify the problem? Do tricyclics help or hurt? Which SRI gives you the most trouble?
Does melatonin make you more depressed?
If I were in your situation, I would try low-dose Seroquel first. The dose must remain low enough such that the accumulation of norquetiapine (an active metabolite of Seroquel) remains negligible. Otherwise, we see it inhibit enough NET and possibly worsen insomnia. I wonder if Seroquel offers 5-HT2c antagonism. I bet it does. This would provide an explanation for why Seroquel works so fast to facilitate sleep. Of course, it could be the antihistamine effect.
If you do indeed suffer from MDD, perhaps your depression is of the endogenous/melancholic subtype, for which insomnia is a prominent symptom. The most common sleep pattern to occur in endogenous depression is early-morning awakenings, Generally, the morning brings the most severe depressive state of the day; with an improvement to be seen in the evening.
This has been quite a rambling post. I hope it makes some sense.
- Scott----------------------------------------------
Post Script:I decided to look into the possibility that Seroquel possessed 5-HT2c antagonism properties. As I noted above, this could explain why Seroquel often acts as a potent sedative/hypnotic. Well, the Seroquel (quetiapine) molecule does not act this way. However, its metabolite (norquetiapine) does. With so little D2 blockade occurring at low dosages, one could make an argument to use Seroquel as a sleep aid.
http://www.ncbi.nlm.nih.gov/pubmed/20931407
Some see things as they are and ask why.
I dream of things that never were and ask why not.- George Bernard Shaw
poster:SLS
thread:1000238
URL: http://www.dr-bob.org/babble/20111016/msgs/1000287.html