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  1. Hi everyone I have serious Bipolar II depression, and my pdoc recently put forth the idea of trying a new drug, Trintellix (Vortioxetine). It hasn't been on the market for very long, and as the old adage goes, "Wait for a new drug to be out for 7 years before you take it." Well, this one has been on the market for 3, so I'm trying to learn more about it and I'm having a hard time finding anyone who's actually taken the drug. My main concern is the number of receptors it hits. First-generation anti-depressants typically only hit 1 receptor. Newer anti-depressants, like Effexor, hit 2. But Trintellix hits 7, and that worries me. It worries me because I'm prone to having withdrawals from just about every drug I've ever been on, and I am also medication-resistant, which means I go on a new drug, it may work for a few months, then it "poops out" and I have to come off it, thus experiencing the withdrawals. Effexor was awful to come off of, and it only hits 2 receptors. This new drug hits 7! It almost reminds me of an atypical anti-psychotic in terms of how many receptors it hits. It's as if Big Pharma decided to package what is essentially an anti-psychotic as an anti-depressant to get away from the stigma that anti-psychotics have developed over the years given their side effects. When I came off of Zyprexa, I had the worst experience of my life and ended up in the emergency room. It took 2-3 months for the W/D to stop. Is Trintellix anything like Zyprexa, or any other anti-psychotic for that matter? From what I can tell, Trintellix hits 7 receptors, and Zyprexa hits 31 ... does that sound about right? I got this from Wikipedia: Trintellix: Target Affinity Functional activity Pharmacodynamic action Ki (nM) IC50 / EC50 (nM) IA (%) SERT* 1.6 5.4 — Inhibition NET* 113 — — Inhibition 5-HT1A* 15 200 96 Agonist 5-HT1B* 33 120 55 Partial agonist 5-HT1D* 54 370 — Antagonist 5-HT3* 3.7 12 — Antagonist 5-HT7* 19 450 — Antagonist β1-adrenoceptor 46[6] — — — Zyprexa: Receptor Ki (nM)[63] Biologic action and notes[64] 5-HT1A 2282 Antagonist. 5-HT1B 585 ? 5-HT1D 1061 ? 5-HT1E 2209 ? 5-HT2A 2.4 Inverse agonist. May underlie the "atypicality" of the newer antipsychotics like olanzapine. May contribute to sedating effects. 5-HT2B 11.9 Inverse agonist/antagonist. 5-HT2C 10.2 Inverse agonist. May underlie the appetite-stimulating effects of olanzapine. 5-HT3 202 Antagonist. Possibly responsible, at least in part, for its antiemetic action. 5-HT5A 1212 ? 5-HT6 8.07 Antagonist. 5-HT7 105.2 Antagonist. α1A 112 Antagonist. Likely responsible for the orthostatic hypotension seen with its use.[64] α1B 263 Antagonist. α2A 315 Antagonist. α2B 81.8 Antagonist α2C 28.9 Antagonist. M1 26 Antagonist. Likely the chief receptor responsible for the anticholinergic effects seen with olanzapine's use.[64] M2 63.5 Antagonist. M3 52.67 Antagonist. Possible role in type 2 diabetes side-effects.[65] M4 17.33 Antagonist. M5 7.5 Antagonist. D1 70.33 Antagonist. D2 3.00 Antagonist. Likely responsible for the therapeutic effects of olanzapine against the positive symptoms of schizophrenia.[64] D2Long 31 Antagonist. D2Short 28.77 Antagonist. D3 47 Antagonist. D4 14.33 Antagonist. D5 82 Antagonist. H1 2.19 Inverse agonist. Likely responsible for the sedative effects of olanzapine.[64] H2 44 Antagonist. H4 >10000 Antagonist. So it appears that Zyprexa hits a whole swath of the brain that Trintellix doesn't touch, so it's not like Zyprexa or other anti-psychotics then? It's still overlapping over the same 7 receptors as Trintellix, which makes me think that tardive dyskinesia could potentially be an issue. Trintellix has only been out for 3 years, so the number of patients from whom such statistics would point to tardive dyskinesia are unavailable simply because not enough people have taken the drug. Zyprexa, by comparison, has been on the market for much longer and likewise we have better stats as to the likelihood of developing tardive dyskinesia. Another thing, since it's so new, it hasn't been properly studied as to how it treats anxiety and OCD, both of which I have severely. Do any of you know if it helps with OCD/anxiety? Have any of you taken Trintellix? Can you share your experiences with me, and if you had any withdrawals coming off of it? Can anyone speak to the above information I provided regarding the receptors? If a single-receptor AD causes me W/D (such as Prozac), and a double-receptor drug like Effexor was even worse (way worse), what will a 7-receptor drug do? As always, thanks guys troop
  2. Hello, I'm on Trintellix/Brintellix (Vortioxetine) 15mg and Valdoxan (Agomelatine) 25mg. I've got a history of being very sensitive to side effects and have tried a ridiculous number of medications. Currently I'm having sexual problems which have the potential to ruin my life and my beautiful relationship. The conflict I'm going through is of course that depression can ruin my life also so I'm very very torn. Does anybody have any idea which is more likely to be causing the numbness in my clitoris out of Brintellix and Valdoxan? I'm willing to put up with side effects within reason, but not this. To me, it would be like eating without taste. Any insights would be much appreciated. I do discuss all of this with my doctor but I feel as if I'm not being taken seriously.
  3. Hello everyone! I've been noticing a lot of sexual dysfunction with the medications that I'm taking right now: oxcarbazepine, fluoxetine, loxapine, lisdexamfetamine. I'm inclined to think that it's the fluoxetine that's causing it. I have very little if any libido. I have difficulties getting an erection and if somehow I do manage to get one, keeping it up is even more problematic. And climaxes are....well....anti-climactic to say the least. I've only noticed sexual dysfunction this bad when I was on Lexapro. The only SSRI I ever took that really didn't cause any sexual dysfunction was Viibryd if I recall correctly. But Viibryd gave me a hyper-active GI and diarrhea. I don't think I can tolerate that again just to deal with sexual dysfunction. So I'm coming on here to ask those who take Trintellix if they feel that there is less sexual dysfunction compared to other serotonergic drugs that they have taken like the other SSRIs. Also would like to say that I feel like loxapine and lisdexamfetamine definitely help my libido. I notice it when I go up on loxapine especially. There's a theory in the psychiatric community that sexual dysfunction can be tempered with 5HT1A agonism or 5HT2A antagonism. Currently, loxapine does antagonize 5HT2A but it is also a minor antagonist at 5HT1A as opposed to agonist. I'm wondering if the 5HT1A agonism from Trintellix might do me some good. Also, I'm not open to switching the loxapine to something with 5HT1A agonism. The loxapine has to stay. The antidepressant is up for negotiation. Looking forward to everyone's thoughts.
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