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browri

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  1. Well @Iceberg we're doing it. The mirtazapine part at least. Started 7.5mg this past Tuesday evening. Increase to 15mg this coming Wednesday the 20th. Then appt with pdoc on the 26th to likely increase further to 30mg. Fingers crossed.
  2. No I certainly do think that combining two antidepressants in bipolar disorder carries an even higher risk of cycling than one does alone. My hope is that mirtazapine as a baseline antidepressant will carry a lower risk than an SSRI or an SNRI, but the beauty of mirtazapine is that if it is dosed appropriately, you should theoretically be able to add 20mg or 40mg of duloxetine to it in times like seasonal depression when the mirtazapine alone isn't enough I also keep in mind that I've technically been taking two antidepressants for years now. I think anyone who has taken Rexulti can vouch that it certainly has antidepressant effects but it isn't a very good mood stabilizer. So with Trintellix+Rexulti together, I never stopped to consider that I might be a little out of control. Now I'm curious to explore the other end of the spectrum, which is mirtazapine, as a potent antihistamine and blocker of 5HT2 and alpha-2 receptors should provide that calming antidepressant effect I felt that I got from olanzapine but become more stimulating as you increase, which is not something olanzapine could really do unless you had fluoxetine on-board. I think as people with bipolar disorder, we constantly live in risk, and our treatment is about managing that risk. For me, I think I haven't been appropriately managing the risk that is Trintellix+Rexulti, and it has culminated in a manic episode with lots of drinking, extreme irritability, etc. Drinking in particular, mirtazapine appears to be very good for depression with comorbid alcohol abuse issues due to its sedative effect.
  3. Oh no definitely not a combo. To be clear, the manic episode and its corresponding symptoms have largely resolved with a few days of just Depakote and Klonopin. So I do think he will re-introduce an antidepressant today (appt moved up to 11:15AM Eastern), but I'm hoping for a different one. Early on in my treatment, we realized that the doses of atypical antipsychotics I needed to control my mood symptoms were doses I couldn't tolerate due to side effects. However, I can tolerate fairly high doses of anti-convulsants which do a fairly good job at controlling my mania. Right now without an antidepressant on-board and just doing Depakote/Klonopin/Vyvanse, I'm cool as a cucumber. But invariably as the half-lives of Trintellix and Rexulti wear off (2-3 weeks for total wash-out) I will likely start to feel depression again. It is the middle of Winter and I just always generally learn towards the depressive side of things. I'm wondering if I'm finding something similar with my antidepressant. Historically, my depression responded really well to olanzapine, which is another 5HT2A/2C antagonist and alpha-2 antagonist. I'm wondering if it will respond well to mirtazapine due to the similar pharmacological qualities, not to mention mirtazapine is also a 5HT3 antagonist like Trintellix, which should help with depression as well. Antidepressant effect through antagonism overall. THEN, if I get to 30mg on mirtazapine and go for several weeks and find it's just not enough, we add back in an SNRI in small increments. My preference would be to just drop in at 50mg of desvenlafaxine OR start at 20mg of duloxetine and increase every few weeks to a max of 60mg. Also, I would maintain the current increased Depakote dose as well as the Klonopin to ensure mood stability while we test this theory. Admittedly, I also want to find a combination that doesn't make use of an antipsychotic at all because I don't like dopamine antagonism and my stimulant constantly fighting back and forth to keep me focused.
  4. Looking to hear different experiences combining mirtazapine with any of the following: venlafaxine, desvenlafaxine, duloxetine, bupropion, or any other similar norepinephrine-heavy antidepressant. I was taking a combination of Depakote/Trintellix/Rexulti/Vyvanse. Have been experiencing some serious mania and heavy drinking and recently discontinued the Trintellix+Rexulti until my pdoc appt this coming Wednesday when we can talk about it in greater depth. We may decide to continue Trintellix, Rexulti, or both. However, I am also seriously considering other options if my pdoc will consider them, this being one of them. Currently, to bring the mania in check I've been taking Depakote ER 1500mg at bedtime and Klonopin up to 1mg/day divided tid. I've also been continuing my Vyvanse so that I can continue working. My desire for alcohol has pretty much disappeared over the past three days as these changes have set in. I feel kinda slow and my husband thinks I'm mopey, but I'm not irritable or snappy, and I'm still getting things done around the house and being productive. I'm signed into work and (sort of) getting things done. So in that regard, I'm being a better human being than I was before I suppose. But I know this is unsustainable. My last doses of Trintellix+Rexulti were Thursday evening, and I know that they have long half-lives. It'll take some time before real depression rears its ugly head again, but it will happen. It always does, and I kinda want to get in front of it. The reason why I ask about mirtazapine, especially in the context of norepinephrine reuptake inhibitors is because in the past, my depression has responded well to olanzapine, which has some strong 5HT2 and alpha-2 antagonism like mirtazapine. They also share potent antihistamine effects, but mirtazapine isn't a considerable anticholinergic so even though there's weight gain, there shouldn't be considerable effect on "metabolics". Pair that with the fact that my favorite antidepressants were always the SNRIs. They were far more motivating than any other antidepressant I took, Trintellix being the exception. Mirtazapine also has a lot of data for depression and comorbid alcoholism, and if I get up to 30mg or so and it isn't enough, I can always add duloxetine in 20mg increments if my pdoc is open to it. Thoughts
  5. Fortunately EMRs these days do help doctors to catch med interactions before they happen, but you certainly can't always count on that. Usually pdocs know about carbamazepine's (CBZ) enzyme induction. They are familiar with the liver CYP isoenzyme system because it metabolizes a vast majority of medications. So with CBZ, double the dose of everything else. Same goes for phenytoin's inhibition of the same enzyme system, half the dose. But lamotrigine is metabolized via glucuronidation, which is sometimes less obvious, and valproate's inhibition of glucuronosyltransferase isn't is commonly known because it doesn't cause a significant amount of other med interactions due to the fact that not a ton of medications go through that process or rely on it exclusively to clear the body as stated above. Really the only reason it's so important in this particular case/context is because of lamotrigine and SJS (Stevens-Johnson Syndrome). But most importantly, if there's one thing I've learned so far in almost 8 years of bipolar treatment myself is that you can't trust the doctor to know everything. They're only human.
  6. No problem. Looking back on that post from last night I was a bit hypomanic and it was a tad of a brain dump, but a more succinct answer to your question is that all three (mirtazapine, quetiapine, tricyclics [e.g. doxepin or amitriptyline]) are very potent antagonists of histamine in the brain in small doses. In the central nervous system, that's responsible for wake/sleep. All three are strongly pro-adrenergic with increasing doses making them all stimulating in the mid-range, but at the top of the range, quetiapine could stand to become sedating again like the bottom end of its dose range due to significant D2 antagonism, which @Iceberg so kindly pointed out. Being devoid of significant dopamine antagonism themselves, mirtazapine and tricyclics will just allow their pro-dopaminergic effects to stimulate those receptors instead of blunting that response as an antipsychotic would. Herein lies the antidepressant effect. Mirtazapine in particular succeeds by cutting brake lines (i.e. antagonizing receptors that would slow the release of other neurotransmitters. E.g. alpha-2C antagonism increases serotonin and norepinephrine, 5HT2A/C antagonism increases norepinephrine and dopamine output in the pre-frontal cortex, which at higher doses should put it on the stimulating portion of the antidepressant spectrum along with bupropion. With all the time I spent writing that last post and this one, I think I've convinced myself to ask my doctor if I can try mirtazapine in place of Trintellix+Rexulti.
  7. I mean @Iceberg you actually covered it really nicely. It's also good that the OP is truly comparing three completely different fruits in this case (actually 3.5, but I'll get to that in a second), as you can stack effects on top of each other to further describe the next. For example, mirtazapine at the bottom of the dose range largely achieves its sedation via antagonism of the histamine type 1 receptors. Histamine controls alertness of various bodily processes. It intertwines beautifully with orexin to regulate the sleep-wake states. It controls the alertness of our immune system (itchiness/allergies). It controls acid production in the stomach (e.g. famotidine is an acid reducer that works by blocking histamine receptors in the stomach lining). So you take this kind of effect and step up to quetiapine, which at the bottom end of the dose range is also largely an antihistamine like mirtazapine, but it also adds alpha-1 adrenergic antagonism, which calms the cardiac system. A step further with tricyclic antidepressants and you introduce anticholinergic effects which are sedating in a wholly different way. Diphenhydramine (common household Benadryl) mediates a lot of its sedation through central histamine type 1 antagonism, but most people don't realize how potent of an anticholinergic it is as well, which contributes to this sedation. And just based off my own experience with benztropine (Cogentin), I can personally say I couldn't do basic arithmetic and my eyes were going out of focus. Anywho........I said 3.5 earlier because quetiapine should be qualified as either immediate release or sustained release. There truly was no need to prolong quetiapine's presence in the bloodstream by creating an extended release tablet. What the manufacturer hoped to achieve was increased exposure to the metabolite, norquetiapine. This would have made Seroquel a stronger 5HT1A partial agonist, 5HT2 antagonist (broad-spectrum), 5HT7 antagonist (serotonin auto-receptor), while also having less adrenergic antagonism, more muscarinic acetylcholine antagonism, and more norepinephrine reuptake inhibition. This had the potential to increase Seroquel's efficacy in affective/mood disorders (XR) versus in bipolar disorder and or schizophrenia (IR), the initial target populations for Seroquel. With increasing dosage of mirtazapine, you introduce considerable antagonism of 5HT2A/C, which would contribute to increased norepinephrine and dopamine output. What makes mirtazapine unique is that it also has considerable alpha-2 adrenergic antagonism (auto-receptors) without also blocking alpha-1. This has a net activating effect because blocking alpha-2 receptors will increase the release of serotonin and norepinephrine, but without also blocking alpha-1 receptors, it will feel stimulating like a norepinephrine reuptake inhibitor. This downstream effect that alpha-2 antagonism has on serotonin release also makes mirtazapine an indirect activator of central 5HT1 receptors without inhibiting serotonin reuptake, and this can be very effective for some patients. With increasing dosage of quetiapine (i.e. the "depression range" = ~100-300mg), similarly to mirtazapine, it begins to activate the adrenergic system because quetiapine is a potent alpha-2 antagonist and its metabolite, norquetiapine, is a strong norepinephrine reuptake inhibitor. Whether you take the immediate or extended release, one of the compounds will increase adrenergic tone. At these doses, quetiapine begins to bind to and block serotonin auto-receptors, thus increasing serotonin release in a similar way to mirtazapine. This is in tandem with norquetiapine's direct partial agonism of 5HT1A receptors, which would assist greatly in depressive episodes without the instability risk of serotonin reuptake inhibition. Tricyclics are much the same as the last two, but they add the TRIPLE whammy of also being serotonin-norepinephrine reuptake inhibitors, which has a net-enhancing effect across the board. When you get to the top of quetiapine's dose range, it begins to saturate and block dopamine receptors in a way that makes it more antipsychotic than anything else. Mirtazapine, on the other hand, has little impact on dopamine signaling. It is a ligand for these receptors, but at very low affinity, which is ironic considering that as a metabolite of mianserin, mirtazapine is in fact a structural analogue of asenapine (Saphris). It is not uncommon for atypical antipsychotics like asenapine to cut the proverbial brake lines (such as blocking alpha-2 receptors to increase serotonin and norepinephrine signaling). What is unusual is for a compound to cut the brake lines and not dampen the chain reaction (like blocking alpha-1 and alpha-2 at the same time). Doing the latter would have the net effect of enhancing serotonin signaling but not norepinephrine, and serotonin activation of 5HT2 would reduce norepinephrine output. Good thing mirtazapine is blocking 5HT2 receptors.
  8. This is true. As a general rule, if one is taking a combination of valproate and lamotrigine, the lamotrigine dose shouldn't exceed 100mg unless the doctor is treading very carefully.
  9. Yeah I really like Depakote for maintenance and for what it's worth I also really liked Lamictal. It was so mild, but it wasn't calming enough. Hence going to Trileptal and then to Depakote to make my anti-convulsant more calming so I didn't have to rely on antipsychotics so much to settle me. I still need APs but in lower doses.
  10. I did try this combo like a year or so ago. I didn't get very far with it. I love Depakote and Lamictal has worked for me in the past, but I was trying to make Lamictal work IN PLACE of an antidepressant, and that just wasn't the right thing for me. Current combo of Depakote/Trintellix/Rexulti/Vyvanse suits me well. Personally took a break from Rexulti last year to try Vraylar and went back to Rexulti after about 6 weeks because I couldn't tolerate Vraylar at 1.5mg. However, if anyone were to try it, my recommendation would be to start with 1.5mg every other day for a good while to get a handle on how it makes you feel before you go to 1.5mg daily. It really threw me for a loop.
  11. Depakote does work be increasing levels of GABA in the brain, which can have an overall calming effect. 500mg of Depakote is a pretty low dose, but it is dosed by weight, and some people can get enough of a blood level for it to have some subtle calming effects (25-50 ug/mL). Average dose for Depakote though is 1000mg with many taking higher doses than that. Omg Latuda made me so panicky for the hour or so after taking it and I never understood why. Latuda did calm me a bit but I wouldn't classify Latuda as a calming antipsychotic overall relative to its cohorts. I ended up switching from Latuda because it wasn't doing a good enough job controlling my irritability and agitation.
  12. While you can certainly ACCOMPLISH what you're describing with the correct medications and the correct timing, that doesn't necessarily mean it's good for you or will always be reproduceable. Due to changes in receptor sensitivity and subsequent up- or down-regulation in the genes that code for those receptors, with increasing frequency of these manic "trips" it would become harder and harder to induce that manic state without pushing yourself too far into mania where you experience "the bullshit" and similarly harder and harder to pull yourself out. What you're describing is a dangerous game because while one may be able to pull out of it once or twice, you keep doing it and it won't always work the way you'd hoped.
  13. Slower than that even. Trintellix has a half-life of ~66 hours. For a compound that doesn't inhibit its own metabolism, you can simply take the half-life and multiply by 5.5 to determine the time it takes to reach steady state after chronic administration. So if you start Trintellix at 10mg and stay at that dose, you can expect to reach steady state in ~15 days after starting the medication, that is 66 hours multiplied by 5.5 to get 363 hours, divided by 24 hours to convert to days. Prozac is trickier though. After a single 40mg dose (acute administration), the half-life of fluoxetine is 1 to 3 days (so 24-72 hours), but after 30 days (chronic administration), the half-life is 4 to 6 days (96-144 hours). This is because Prozac inhibits its own metabolism. Fluoxetine is a strong CYP2D6 inhibitor. Imagine if you plotted your blood concentration of fluoxetine on a chart where X is time and Y is the blood concentration. For each day that you take the same dose, the medication should steadily increase until it reaches a steady state concentration after several days of administration. For Trintellix, this happens about 15 days after chronic administration of a consistent dose, but for Prozac, that steady state target is moving with each additional dose you take. In the beginning, the target starts out somewhere between 5-17 days, but by the time you actually reach steady state, 22 to 33 days have passed. But there's another confounding factor. For Trintellix, most of the pharmacological activity is mediated via the parent drug, vortioxetine; but for Prozac, the metabolite, norfluoxetine, plays just as important a role as the parent drug, fluoxetine, and at steady state, fluoxetine and norfluoxetine circulate at relatively equal concentrations. While both fluoxetine and norfluoxetine are both serotonin reuptake inhibitors, fluoxetine also has some affinity for the norepinephrine transporter, norfluoxetine has even more affinity for the dopamine transporter, and they both have considerable affinities for antagonism of the 5HT2C receptor. Taken together, this may explain why Prozac is stimulating at higher doses. This could be another reason why considerable effect isn't seen until after 4 weeks with Prozac, because while you may achieve fluoxetine steady state at 30 days, it can take up to 88 days to achieve steady state of norfluoxetine (half-life of 4-16 days, highly variable, doesn't inhibit its own metabolism but undoubtedly much longer than fluoxetine regardless). So if norfluoxetine is going to play a major role in treatment efficacy, it's going to take a lot longer than 2 weeks to build up, think more like two and a half months. But you see with Prozac inhibiting its own metabolism how that line charting the blood concentration actually curves like a banana (non-linear pharmacokinetics), whereas Trintellix would have a straighter line (linear pharmacokinetics).
  14. If you want to stick with Prozac, it may be worth trying the 40mg dose, and it goes up to 80mg. It started becoming more stimulating for me at higher doses. But if you wanted to try Trintellix, I would also highly recommend. I find it stimulating like Prozac similarly at the higher doses. Although I certainly don't consider it to be a lite version of Prozac. I think 20mg of Trintellix has more kick than 40mg of Prozac, but that's just me.
  15. Been taking it since 2017, and in my experience, no cognitive dysfunction. My thoughts do feel slowed down, but in a good way, not like I'm unable to complete thoughts. Calm. Not like when you take Cogentin and you feel sedated AND you can't do basic arithmetic. I've been at ~65mcg/mL blood level on 1250mg of Depakote for nearly a year. I will caution though that Depakote dosed at high levels can certainly still cause cognitive dysfunction just by the nature of the way it works. It increases the activity of GABA in a few different ways and therefore leans the brain away from glutamate signaling, which is intrinsic to cognitive function via neuroexcitation in tandem with acetylcholine.
  16. I would too. Like I said earlier, I think that if I couldn't take Trintellix anymore due to an insurance coverage issue, I would go to generic desvenlafaxine in a heartbeat over most others except maybe duloxetine (Cymbalta).
  17. Affinity isn't everything. The effect at a given concentration also matters. Something can bind but have little effect or have no effect. As indicated before, someone who takes 150mg of venlafaxine daily will have, at steady state, concentrations of O-desmethylvenlafaxine that are equivalent to concentrations seen on 50mg of desvenlafaxine daily. Venlafaxine has an affinity for the norepinephrine transporter of 2480 nM (nanomoles). However, its IC50 (half-maximal concentration) is 535 nM. This would suggest that while its affinity is low, it is able to elicit an inhibitory effect on the transporter at a range of doses. And at 150mg, it is likely that venlafaxine's inhibitory effect on the norepinephrine transporter is minimal and that the majority of inhibitory effect on NET at that dose is mediated by the metabolite, O-desmethylvenlafaxine. With the above in mind, one would then expect that 300mg of venlafaxine would yield concentrations of O-desmethylvenlafaxine at steady state reflecting a daily dosage of desvenlafaxine around 100mg. This is true. However, O-desmethylvenlafaxine's pharmacology is different. While it does have a greater affinity for the NET at 558.4nM, its IC50 is 531nM, indicating that its affinity for the receptor and its half-maximal concentration are similar and a range of doses may not yield a differential effect. So going from 50mg to 100mg on Pristiq may bring NET inhibition to more of a maximum, going to 150mg may not make a whole lot of sense, hence why they never made a 150mg tablet. Therefore, one can expect that at 300mg of venlafaxine, you would have more of a therapeutic effect (and more side effects) than 100mg of desvenlafaxine. Additionally, you can go to 450mg on venlafaxine and treat some really severe depression where desvenlafaxine generally has no added effect. Additionally, where venlafaxine has an affinity for the dopamine transporter at high doses, desvenlafaxine is devoid of activity. Venlafaxine also can have effects on pain via the opioid system due to its structural similarity to tramadol. Evidence supporting desvenlafaxine's ability in pain does exist, but it's far more sparse. That's not to say that desvenlafaxine isn't a strong antidepressant, because it is. It's an SNRI for starters, and it's starting to be recognized like citalopram as a medication that some people are just ultra-compatible with. BUT, if you're on 100mg of Pristiq and still feel like you need more, then go to 150mg of Pristiq and aren't impressed, don't be surprised. But it may be worth switching over to 300mg of Effexor XR or higher instead if your doctor is open to it.
  18. I suppose high dose risperidone could make one nervous due to the pro-adrenergic effects from blocking certain receptors. Not sure how Risperdal Consta will solve for that. Risperdal is Risperdal. But perhaps he means to try you on Invega (paliperidone) which may theoretically have fewer side effects than the parent drug.
  19. Two recommendations I would make. Firstly, echoing what others have said, cannabis CAN be destabilizing in bipolar disorder. However, if you are properly medicated and you're consuming the right kind of cannabis, it doesn't have to be so bad, and sometimes it helps people. Best to keep the THC lower and the CBD higher. I know CBD doesn't give as much of a buzz, but if you consume high CBD products that still have a little THC in them, you may feel a lot better. I have my medical cannabis card in Pennsylvania and I have two favorite products. The first one is Vireo Indigo Tincture. Which is CBD:THC in a 19:1 ratio. So very low THC but it's still there. The other is Harle-Tsu Remedi RSO by Cresco Yeltrah. The RSO concentrate is 4:1 giving for some more THC that is useful for really difficult agitation or anxiety or when I want to go to sleep. But at the end of the day, I always have more CBD than THC and I generally feel better than I do worse. Another thing to look into is structuring your breathing a bit more. It isn't just about breathing in through your nose and ensuring you take a really deep breath. Try 4-7-8 breathing. Inhale for 4 seconds. Hold for 7 seconds. Exhale across 8 seconds. Do this maybe 2-3 times in a row (i.e. one set of 2-3 reps). You'll find it to be very relaxing in the moment if you need something to help you unwind a bit.
  20. Wow, sounds like you've been getting really jerked around by your care team. A real shame, but such is the nature of healthcare nowadays. I'm surprised and simultaneously not surprised that your pdoc said to either go to the hospital if it was bad enough or go to your gdoc if it was bad but not bad ENOUGH (i.e. not a danger to others or yourself). None of us here are doctors, so we can't give you a direct medication recommendation, but we can provide our experiences and information about these medications that is public knowledge. First and foremost as already indicated, your gdoc through no fault of his own just isn't as well versed in psychiatric care. He's in general practice, and psychiatry just isn't his bread and butter. I'd say it's pretty normal for a general practice doctor to see that low doses of Seroquel (e.g. 75mg) are quite sedating to patients and they believe that translates into manic/mixed control, when that may not necessarily be the case. At doses that low, it largely achieves sedation via 5HT2A antagonism and H1 antagonism, but that isn't mania control. Sufficient occupancy of dopamine receptors to blunt manic episodes isn't achieved generally until like 200mg+. If your gdoc isn't willing to go that far, then you should discuss other options with him. It's also important to not change doses without the supervision of a doctor, even a doctor that may not be as well-versed in psychiatry. As @Iceberg mentioned, if it were lithium, it would be good to do it with your gdoc's supervision so that he could write for the necessary blood work to make sure your levels aren't in the toxic range after a few days of the new dose, as well as assess basic things like kidney function. Those are all things that a general doctor can do. And yes, there may be a delay with lithium until full effect is realized, but it's probably more like 2 weeks and not a month. Lithium isn't an antidepressant. Perhaps full effect on mood may take 2-4 weeks, but effects on mania are usually apparent in 1-2 weeks. I wouldn't recommend having your gdoc change your medications to something else. Optimize doses, yes. Swap them out, no. Your gdoc isn't going to have the tribal knowledge to accurately decide which way to go next. You also don't want to lose the progress you've made with your pdoc. Your pdoc is more likely to be receptive to hearing that a gdoc increased doses of the current medications to achieve better symptom control rather than swap them out because he thinks he has a better idea than the pdoc does. Catty I know, but this is the prideful side of medicine. If it were me, and I were to talk to my gdoc about increasing the doses of medications that my pdoc prescribes, for the fastest effect, I would ask for an increase to Seroquel because between lithium or atypical antipsychotics (AAPs), the latter have far more evidence in favor of RAPID effect. However, Seroquel stands to cause more weight gain than lithium and probably more sedation. Zyprexa (olanzapine) likely will cause more weight gain than Seroquel and even more metabolic dysfunction. So if you can stand to wait a bit, it may behoove you to optimize the lithium dose because there is more positive evidence in its favor in the long term. You're only on 600mg and many go to 900mg or higher. You should be able to get either 300mg or 450mg tablets which should allow you to do 2x450PM, 450AM/450PM, 300AM/2x300PM, etc. Now, when you have your next pdoc appointment, if you find that you aren't tolerating the increase to either lithium or Seroquel (or both), maybe you should talk to your pdoc about valproate again. For those who don't tolerate lithium well, valproate is often a good alternative although there may be less evidence in valproate's favor from a maintenance perspective. However, valproate's strong point is fighting mixed mania, a prize that AAPs take home most of the time. Valproate seems to be better than lithium in this regard but maybe not as good as AAPs. It also doesn't seem to be effective at all for most bipolar depression, except when the core of that bipolar depression is mixed or anxious distress, similar to what you are describing. Therefore, valproate may be worth considering if you've taken it before and tolerate it. Personally, I LOVE valproate. HATED lithium. LOVE VALPROATE. It's literally the backbone of my cocktail. We cycled through several antipsychotics trying to find one that I could tolerate at the doses I needed to control my symptoms. But we couldn't find one. Every single one caused akathisia before I could achieve appropriate mood control. But with valproate, my baseline is so much lower that I don't need mood stabilizing doses of AAPs, the lower antidepressant doses of AAPs are sufficient, hence I now take 1250mg divalproex with 2mg Rexulti and 15mg Trintellix.
  21. If you took Effexor XR at 150mg then you have a fairly good idea what Pristiq 50mg feels like already except now you'll theoretically have fewer side effects. However, despite Pristiq's improved tolerability, it shouldn't necessarily be misconstrued as a more powerful antidepressant as well. In fact, it's generally regarded that slightly reduced efficacy with Pristiq in some patients is the tradeoff for getting improved tolerability. Like they now want to try you on Pristiq first because it is an SNRI and inherently stronger in some ways than an SSRI, but if you tolerate it and need more oomph after 100mg then they just cut you over to Effexor and titrate you up to 300mg from there. But 300mg of Effexor is generally stronger than 100mg of Pristiq despite the theoretical equivalency of 100mg desvenlafaxine being produced in the human body from 300mg of venlafaxine. I hope Pristiq does well for you. I'm on Trintellix now for depression, but if I had to pick a generic antidepressant that I would go back to if this was no longer covered, Pristiq would be it. I absolutely loved it. Only reason I stopped taking it at the time was because it was still brand-only and I was switching to a new insurance that wouldn't cover it. So I had to go to Effexor 150mg because that was covered. Worked well but kinda pooped out, at which point I went to Cymbalta 60mg until I started seeing a new pdoc and was properly rediagnosed.
  22. correct on both counts. between alpha-2 adrenergic antagonism increasing serotonin and norepinephrine output, 5HT2 inverse agonism increasing norepinephrine and dopamine output, and pre-synaptic D2 antagonism at low doses (D2S) increasing dopamine output; this is basically how pdocs pull out the brake lines on some of these neurotransmitter systems. In this case, you can further increase serotonin release via the alpha-2 antagonism like you said. And it's possible to achieve higher serotonin output and central 5HT1 desensitization with that extra oomph from an AAP to boost the AD. Usually the goal with OCD is to achieve the highest SERT occupancy tolerable by the patient to achieve the highest serotonin signaling to desensitize serotonin receptors which would reduce dopamine release in the long-run. This would make for less obsessive tendencies, but then you might be left with anhedonia like you said. So you'll have to find the balance between no anhedonia and no obsessive ruminations because the space between the two is very gray.
  23. So the way Abilify Maintena works, according to their site: - Comes in 300mg and 400mg pre-filled syringes or vial kits for custom dose adjustments - Usually given 400mg in tandem with 10-20mg of oral Abilify for 2 weeks. -If a lower dose is needed, then use the 300mg syringe or a custom dose with the vial kits. If your pdoc said she gave you a lower dose to make sure there weren't any hiccups, she probably gave you the 300mg dose. However, if you've been taking 30mg oral Abilify up to this point, I imagine you'll end up needing that 400mg dose. So if your first month on the 300mg dose doesn't go so well, then your pdoc will likely do the 400mg dose next month. If you still need more than that, then the third month you would move to Aristada, which comes in 4 different strengths combined with 3 different dosing periods for 5 different "doses": - 10mg day = 441mg / 4 weeks - 15mg day = 662mg / 4 weeks -OR- 882mg / 6 weeks -OR- 1064mg / 8 weeks - 20mg+ day = 882mg / 4 weeks The next logical step from 400mg/4wk Abilify Maintena would be 662mg/4wk Aristada, then 882mg/4-6wk.
  24. The reason that quetiapine and risperidone are oft-used in treatment-resistant OCD is because it is vaguely understood that while dopamine acts as a pleasure chemical and part of the brain's task-reward system, in the hands of someone with OCD, dopamine can also act to chemically reinforce obsessional tendencies. Anything that promotes dopamine can in fact exacerbate obsessional tendencies in individuals who are susceptible. 5HT2A antagonism from AAPs can promote norepinephrine and dopamine release, which can agitate obsessional tendencies in addition to its antidepressant qualities. Amphetamines typically exacerbate obsessive compulsive disorders likely via dopamine efflux. So on and so forth. Think about how addictive cocaine is and how it can reinforce certain behaviors. Now imagine a brain that metaphorically self-administered itself little bits of a similar rewarding substance to reinforce obsessional tendencies, and this is kind of the brain on OCD. Clomipramine was always regarded as the gold standard for OCD because it had among the highest affinity for the serotonin transporter (next to paroxetine among a few others) and could be dosed to insanely high blood levels that would saturate the transporter to a degree that couldn't be achieve with other serotonin reuptake inhibitors. In addition, chronic inhibition of the serotonin transporter and subsequent chronic stimulation of central serotonin receptors (e.g. 5HT1A) leads to a downstream reduction in the release of dopamine. This may seem strange, but this is an important part of the antidepressant effect. You are less likely to obsess over the things that bother you when dopamine signaling is lower. Inadvertently, however, you cause anhedonia because you intrinsically stop CARING. Hence pairing an antidepressant with an AAP to promote norepinephrine and dopamine release while simultaneously stabilizing dopamine receptors (dopamine antagonism / partial agonism), thereby preventing any of the other problems caused above. In addition, clomipramine is a weak, albeit modest, dopamine antagonist. This may underscore its capability against OCD at high doses. The same can be said for risperidone. Lower doses preferentially antagonize pre-synaptic dopamine auto-receptors (D2-short) and 5HT2A heteroreceptors, both of which lead to a release in dopamine. With escalating doses, antagonism of post-synaptic dopamine receptors (D2-long) dampens this antidepressant effect. From person to person it varies, but it happens somewhere <2mg. It's important to recognize that this blunting could very well be an important part of your effective treatment, and it shouldn't be written off.
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