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Skeletor

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  1. Why does Mirtazapine cause Restless Legs Syndrome? Mirtazapine is known to often provoke restless legs syndrome (RLS). Mirtazapine has an approximate 30% chance of inducing it; by comparison, paroxetine, sertraline, and other psychiatric medications only have an approximate 5% chance of causing RLS symptoms. Why is Mirtazapine prone to causing RLS? It's very interesting, especially that high percentage. No one seems to know why. They say that it might be due to its strong antihistamine properties. Some experts have proposed that it is due to its 5HT2 antagonist properties. But then other strong antihistamines and 5HT2 antagonists should also be prone to cause RLS, e.g. Amitriptyline, Nortriptyline, Doxepine etc., but they don't seem to cause it as frequently as Mirtazapine. One could argue that it is due to anticholinergic properties, which might have a counterbalancing effect. Some say that it may be Mirtazapine's pro-noradrenergic properties, but shouldn't we see it with other NRIs and pro-noradrenergic drugs? Many questions, no definitive answers...
  2. Amitriptyline as a tertiary amine is, when counting in its metabolite Nortriptyline, more noradrenergic than serotonergic... all in all.
  3. Aren't long half lives good when it comes to psychotropics? Better than those SNRIs (Venlafaxine, Duloxetine) with their ridiculously short half lives and interdose-withdrawal... !?
  4. It is one of the very few atypical antipsychotics that I would be willing to try... as adjunct for depression / for mood stabilization. Quite interesting drug.
  5. Okay, then "Abilify" might be interesting.... partial agonist at D-Receptor(s), partial 5HT2C agonist, weak sedation @H1... Partial agonist at 5HT1A...
  6. It would seem so, at least according to many studies... Gillman regularly mentions that his patients did substantially better on TCAs than on SSRIs (Sertraline might be an exception). Especially Amitriptyline, Clomipramine and Imipramine seem to be superior in effectivity. Is it wise to completely shun those very effective older antidepressants?
  7. Something like Olanzapine (or Aripiprazole) might be better suited than "Seroquel"... Olanzapine has some potent 5T2 antagonism that should ease the side effects of Imipramine... Seroquel is primarily a strong antihistamine with some moderate NRI action, but you've already get enough NRI action with Imipramine. Alternatively Cyproheptadine if you can get it. Mirtazapine would also be a good choice.
  8. https://en.wikipedia.org/wiki/Amitriptyline https://en.wikipedia.org/wiki/Nortriptyline Both are quite similar, and that is no surprise, given that Notrtiptyline is Amitriptyline's major metabolite. When comparing both, we can ascertain the following: Amitriptyline has somewhat more SERT blocking going on, so might be slightly more "serotonergic" than Nortriptyline, although I am not quite sure if clinically relevant. Both are equally strong NRIs and 5HT2 antagonists. Amitriptyline is a stronger ALPHA1 blocker compared to Nortriptyline, so might cause more postural hypotension. Amitrptyline is a stronger antihistamine than Nortriptyline, so might cause more sedation and appetite. Amitriptyline is a stronger anticholinergic than Nortriptyline, so will probably cause more side effects. (Although stronger sedative and anticholinergic properties might be welcome, depending on the condition) What I am interested in: Who's been on both and how did they compare? (not only theoretically, but practically) binding affinities: picture source: https://abload.de/img/nortgpk1f.png
  9. https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/clomipramine-tryptophan-and-lithium-in-combination-for-resistant-endogenous-depression-seven-case-studies/F3A1B19433959744DCF32C36C7B4A28F# Unquestionably an extreme combination, but it seems to exhibit powerful antidepressant effects. Clomipramine on its own is regarded by many as maybe the most powerful non-MAOI antidepressant, at least in clinical practice and inpatient care, although the side effects can be quite rough, but combined with Tryptophan and Lithium it seems to be further boosted in its effect size and response rate. Maybe worth trying before hopping on ECT / MAOIs... One has to be careful because it is a small sample case "study", but nonetheless quite interesting to read. I encourage all those who have a view or experience to share it with us, regarding the aforementioned medications and especially the combination. Greetings!
  10. In my experience? No.... Clomipramine is probably the strongest SNRI on the market. Its NRI effect might ease the anhedonia to some degree...
  11. They've even done Tranylcypromine + Amitriptyline ^^ https://www.ncbi.nlm.nih.gov/pubmed/30106881 How so?
  12. Nortriptyline seems to be a popular addon. SSRI + Nortriptyline MAOI + Nortriptyline
  13. Both are second-generation SSRIs, both exhibit minimal drug interactions via Cytochrome P450, both are the most prescribed SSRIs and are considered first line antidepressants. Who's been taking both and what were your experiences? (How did they compare to each other?). I am looking forward to read your experiences... Which one did you like more?
  14. With 75mg of Clomipramine you get like 95% SERT blocking... (One exception: rapid metabolizers). This should be more than enough for the run-of-the-mill patient.
  15. Apropos that stimulation / tickling. It felt more like some form of odd genital stimulation. I didn't have typical sexual arousal or sexy thoughts when it happened. It was really an unpleasant intrusive feeling that I had to get rid of via triple masturbation. It didn't feel like hypersexuality or normal (heightened) form of libido. It was like a tingling... it doesn't hurt you, but it is no pleasant feeling. Strange thing is that it also happened on higher dose of Promethazine (30mg), not only Mirtazapine.
  16. On 15mg of Mirtazapine I had RLS and some strange tickling feeling in my lower stomach. (I masturbated a lot to get rid of it.) On 15mg of Promethazine I am fine, but anything higher than 25mg and I get RLS and that tickling feeling. What is going on? Which mechanism is involved? https://academic.oup.com/sleep/article/43/2/zsz223/5610750 "It simply seems like histamine might have a role in RLS. Could it be as simple as that blocking histamine H1 receptors is bad for RLS? Or is it due to some kind of indirect interaction histamine has with dopamine?" It would seem that this antihistamine theory might be true at least to some degree, although there are so many theories on RLS that it is difficult to see through it. Especially when you have antihistamine properties and anti-Dopamine properties rolled into one drug. But Mirtazapine doesn't seem to have anti-Dopamine properties, so leaves the antihistamine action as culprit of RLS.... Promethazine has some anti D2 action, but it is ridiculously weak: D2=250, 5HT2A=170, H1=1 [nM] from Gillman's website. I doubt that it will do much in that regard.
  17. Supposedly it inhibits 80% of SERT transporter at 10mg... that is one hell of a potent drug. So with 75mg you probably would have 95% SERT inhibition. https://en.wikipedia.org/wiki/Clomipramine#Pharmacodynamics There is also the notion that many TCAs might be "overdosed" in general... Yes, that is a good combo. Makes sense to add Lamictal.
  18. Clomipramine can be rough at the beginning. Remember: it is the most potent SNRI + a strong anticholinergic. I would give it some more time. 75mg should be enough. No need to go higher if you don't have OCD.
  19. I welcome you to rate all the psychotropic drugs which you took in the past or are taking in the present. A short explanation of your experience with the drug(s) would be helpful, so that we better understand your rating. Oh, and please tell us which conditions you treat(ed). Thanks. Rating Scale is from 0 to 5... "zero" being the worst, "five" being the best. _______________________________________________________________________________ Sertraline 2 / 5 - subtle effects. Did help with psychosomatic ailments, derealization and cognition, but caused SSRI-typical apathy & indifference. Not sure if it did anything for my social anxiety and psychomotor agitation. At most minor effects. I did take it for two years. Mirtazapine 2 / 5 - elephant tranquilizer. Didn't like the severe sedation. Didn't sleep well on it, bad dreams. Caused RLS. Was good for appetite, weight gain and IBS. I was on it for two weeks. Promethazine Syrup / Drops 20mg / ml | 3 / 5 - I rather liked that one. At a lowish dose (15 drops or so) it has a nice calming effect on me, without sedating me too much. Lowers anxiety and agitated states. Brings order into chaos. Good for appetite and stomach. I take it occasionally. N-acetylcysteine (NAC) 2.5 / 5 - Is a good supplement. Heightened focus, less derealization, world seems more colorful. Interesting stuff. Definitely worth a try. .............................. Conditions treated: Anxiety, depressive states, psychomotor agitation, somatization disorder.
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