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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?
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