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    Bethlehem, PA

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  1. It's interesting. My pdoc takes this tactic as well. Letting me bring something up at a few different appointments spread out over the course of a few months to a year before he takes action on the suggestion like he's hoping things will just work out and I'll forget about it. To be fair, this isn't a terrible tactic. The less change the better as a general rule. Consistency is key. But sometimes you do need to take that next step, and it's good to see that your pdoc is at least still open to the suggestion even if getting her to act on it is difficult. If your pdoc gives you the choice of risperidone or aripiprazole, I would say low-dose risperidone or quetiapine makes more sense than low-dose aripiprazole, which can be quite activating and can speed up your thoughts. I don't see aripiprazole being good for OCD unless you went to moderate doses like 5-10mg because it takes a higher dose of aripiprazole to get to the "calming" effects. Below 5mg, it's generally pretty activating. Brexpiprazole (Rexulti) on the other hand is calming in the lower doses. So once Rexulti comes out in the EU, and if risperidone or quetiapine (or both) don't work out for you, Rexulti might be a good next step.
  2. I'll take a stab at this one. The goal with pharmacological treatment of OCD is to increase serotonin signaling. The standard of care is to do so using a serotonin reuptake inhibitor. Typically, 60-80% occupancy of the serotonin transporter is requires to achieve a response in depression and other mood disorders. However for OCD, maximal transporter occupancy is required to a magnitude of about 90% or higher in some cases. Clomipramine is so often used in this case because of its ultra-high affinity for the serotonin transporter, which is bested pretty much only by paroxetine. When serotonin signaling is increased via inhibition of the transporter, activation of serotonin receptors causes inhibition of downstream dopamine signaling/release. However, serotonin and dopamine receptor sensitivity can be semi-restored after chronic treatment. That is just part of the brain's homeostasis. Because of this, there may come a point when the antidepressant "poops out". The beauty of aripiprazole is not only its high affinity for the dopamine D2 receptor but also its high intrinsic activity. Because aripiprazole is more of an agonist than an antagonist (i.e. its intrinsic activity at D2 is ~60%), the agonist effect at pre-synaptic D2 receptors (i.e. D2S) will further suppress dopamine release. Dopamine is a pleasure chemical, but that isn't all it does. It's part of the reward system. It reinforces our actions. So when you do something bad or risky and it causes a rush a dopamine, you feel like a "bad boy" and it's exhilarating. For people with OCD, overactive dopamine signaling can actually subconsciously reinforce a person's obsessions and compulsions. Stimulants can cause similar behaviors due to their enhancement of the norepinephrine and dopamine systems. So the goal of the SSRI is to enhance serotonin signaling to inhibit dopamine signaling, and aripiprazole further dampens the dopamine pathway in those where indirect dampening via an SSRI is insufficient.
  3. Are you happy with where you are now? Lithium+Lamictal is a solid combo for many people and should be sufficient, but as we all know, things are seldom perfect.
  4. Shouldn't be an issue. You should definitely talk with your pdoc about it but theoretically the low-dose Seroquel will block histamine H1 receptors and 5HT2A receptors more potently than Vraylar and will assist with sleep since Vraylar may cause insomnia. Only thing is that H1 antagonism is what most likely causes next-day sedation with Seroquel and you may be better off going with trazodone as it is a potent 5HT2A blocker but not nearly as potent of an antihistamine as Seroquel. It may give restful sleep without the hangover.
  5. You'll definitely start to notice changes in Week 1. But much like antidepressants, effects on mood are mediated through changes in gene expression and sensitivity of the various receptors. Those changes will continue to occur up to 4 months from initiating Vraylar. So yes, in the beginning you may notice some stimulation from it, but you may also notice your thoughts calm down at the same time. So the impact on anxiety may be very quickly apparent but any impact on depression could take a few weeks. Have you decided to start it yet?
  6. I agree with HydroCat's assessments here. 1. There's nothing in your cocktail doing 5HT1A agonism. Some people have described buspirone (Buspar) as being good for anxiety but activating as well in some ways due to the downstream dopamine release. If you talk to your pdoc about buspirone, the recommendation would be to keep the dose lower to avoid the dopamine receptor blockade that buspirone can have in higher doses. Alternatively, you could replace the sertraline (Zoloft) with vilazodone (Viibryd) or vortioxetine (Trintellix) to get the 5HT1A agonism. I personally found vilazodone to be quite activating, and I find vortioxetine to be similarly activating, but vortioxetine has actually improved my sleep, whereas if I didn't take vilazodone before 9AM, there was no sleeping that night. If you do add on buspirone to your current sertraline+clomipramine cocktail, you could talk to your pdoc about coming down on the sertraline to the average dose of 50mg. The 5HT1A agonism from buspirone will make lower doses of antidepressants "go further". 2. Sertraline in higher doses actually has a modest affinity for dopamine transporter (DAT) inhibition similarly to bupropion (Wellbutrin). However, bupropion will likely give you more bang for your buck. You could work with your pdoc to reduce the sertraline to 50mg and add 150mg of bupropion to balance out the cocktail a bit more. Alternatively, you could go for California Rocket Fuel (venlafaxine(Effexor)+mirtazapine(Remeron)) although theoretically, you could achieve a similar effect with any norepinephrine reuptake inhibitor combined with alpha adrenergic receptor type 2 antagonism. If you didn't want to overhaul the entire cocktail, you could talk with your pdoc about a combo of sertraline+bupropion+mirtazapine. Mirtazapine will block alpha-2 adrenergic receptors which will cause downstream serotonin release and thus indirect agonism of 5HT1A. It will also block 5HT2C which will increase norepinephrine and dopamine release. Then bupropion will inhibit the norepinephrine and dopamine transporters (and sertraline will inhibit SERT, and even DAT as well at higher doses) to make those three neurotransmitters persist in the synapse. The net result should be dramatically increased signaling of serotonin, norepinephrine, and dopamine. 3. A very good point...200mg of sertraline is a very high dose and it doesn't surprise me that you feel kind of flat and unmotivated at this point, even with the DAT inhibition at that dose. And you might be moving into risperidone doses that won't help you any further for SSRI-induced anhedonia (e.g. 2mg). Remember that with increasing serotonin, the brain will try to push down dopamine signaling as a balancing act. So you want to work with your pdoc to find a cocktail that strikes a balance among serotonin, norepinephrine, and dopamine. Right now your cocktail is really serotonin heavy, thus inhibiting dopamine neurotransmission and that is compounded by the dopamine antagonism from risperidone.
  7. Yeah and my pdoc is very much of that mindset. He always checks VPA, CMP, and WBC just to make sure I'm not toxic and don't have agranulocytosis, but he doesn't really pay too much mind to what the level actually is if my symptoms are controlled. I spent a good portion of my time on Depakote <50mcg/mL and that was even at a dose of 1000mg. So yeah, my pdoc does dose based on clinical response and tolerability and doesn't hold to the guidelines unless I'm acute in some way. Then we push to 1250mg which actually got me a 69mcg/mL at one point in time. I think they say 80-100mcg/mL is required for acute mania control like if you're inpatient.
  8. Just had my pdoc appt and asked about swapping out the Rexulti and Depakote for Vraylar, but he didn't bite unfortunately. Said to stay the course and if my thoughts feel a bit fast I can bump the Depakote to 750mg on my own. I'm doing pretty decently so not a real compelling reason to change in my pdocs mind.
  9. So I had the appointment this morning. He felt that making any more changes would be overtuning since I'm in a good mood. I'm not depressed but I'm not sub-hypo now that I've reintroduced the Depakote at a low dose. I asked about option #1 where we would slowly increase the Rexulti dose and eventually withdraw the Depakote, but he said he wanted to avoid TD or other EPS like akathisia and that we could justify the very low dose of Depakote because I'm also on Rexulti. He would rather use lower doses of two medications than slim down to just one of them. I also asked about option #2 (Vraylar), and he confirmed his experience with it that it is agitating for some patients. But I also relayed some of the experiences that others have had where it is activating/agitating but stabilizing at the same time. He didn't bite. Wanted me to stay the course: Trintellix 15mg Vyvanse 30mg Rexulti 1mg Depakote 500mg And he said that if I my thoughts ever feel like they're picking up speed that I can bump the Depakote to 750mg on my own without calling him. I can tell that he's seriously thinking about my past experiences with AAPs and that my akathisia threshold is low. He really doesn't want to push the Rexulti unless I need a really quick fix. So much for CBZ and I guess I won't be trying Vraylar, but it's probably for the best. I'm doing good right now and there isn't a really GOOD reason to switch other than my complaints about weight gain, but it hasn't been too serious and we did reduce the Depakote so maybe I'll shed a few pounds.
  10. The reason why SSRIs and SNRIs take so long to kick in is due to auto-receptor desensitization. By inhibiting the transporter, those medications increase serotonin in the synapse, which binds to pre-synaptic 5HT1A auto-receptors and slows down the serotonin pump. Over time, the 5HT1A auto-receptors become desensitized and serotonin release begins again the way it was before starting the SSRI, except the net serotonin activity is much higher. Because mirtazapine (Remeron) mediates its effects through receptor antagonism and partial agonism, the action is much more rapid. This is why mirtazapine is often given in conjunction with the initiation of an SSRI because it will cause an SSRI to kick in more quickly than it normally would and it also helps to treat some of the side effects caused by SSRI treatment such as reduced appetite (5HT2C antagonism), nausea (5HT3 antagonism), or insomnia (H1 and 5HT2A antagonism), and maybe even sexual dysfunction (5HT7 antagonism). It's really hard to make this kind of comparison because trazodone and mirtazapine mediate their sleep effects somewhat differently. They both do so through 5HT2A antagonism, but mirtazapine is a potent H1 histamine antagonist as well, which trazodone is not. This is likely why people find that trazodone has less next-day sedation like your family members said. So trazodone is TECHNICALLY an antidepressant, but it's fallen out of favor for that usage because of its metabolite mCPP (meta-chlorophenylpiperazine), which is a serotonin reuptake inhibitor, serotonin releasing agent, and a serotonin agonist at most all the receptors it touches. As we know that antagonizing serotonin receptors can have antidepressant effects, you can imagine that AGONIZING those receptors would have the opposite effect (except at 5HT1A). mCPP is sometimes sold as a subsitute for ecstasy and it's been reported to not be a desirable experience. So the reality is that the body breaks trazodone down into a compound that actually hinders much of trazodone's legitimate antidepressant effect. The short of it, if you need something for sleep but it also needs to have an antidepressant effect, you're better off with mirtazapine and trying to get to a higher dose that overpowers the antihistaminergic effects with adrenergic enhancing effects.
  11. Interesting. So general consensus so far is that it can do well in the morning. Noted. Any more experiences appreciated!
  12. Not sure. I'm still only taking 500mg of it at this point just so I'm on it and adjusted to it in case he does want me to increase back up, but I'm going to talk to him about either: 1. Slowly increasing the Rexulti by 0.25mg every 2-3 days until I reach 2mg and withdraw the Depakote to see what happens. 2. Titrating off the Rexulti while initiating Vraylar and eventually withdraw the Depakote.
  13. If this has been your experience then you're probably right. But don't be surprised if you have a random headache day here or there.
  14. Saphris is a potent 5HT2C antagonist. That receptor is responsible for mediating satiety (i.e. "feeling full"). When you block it, it makes you more hungry. Activate it and it reduces appetite. However, blocking 5HT2C on its own shouldn't cause weight gain independent of food intake.
  15. More than likely Effexor withdrawal would have shown up already, unfortunately. It's possible you just aren't compatible with Brintellix. However, the fact that Valdoxan gave you a lift might be worth sticking out. Even the two of them together because they operate differently.