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browri

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About browri

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  1. 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).
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. I will also say that if it truly is the motivation of your doctor to help you think about your medication less, then they should be trying to move you towards Aristada which is a prodrug called aripiprazole lauroxil. At the 1064mg dose, it allows for 2 months between injections. Some of the data would indicate that perhaps better symptom control can be achieved with LAIs of compounds that already have long half-lives. For example, the 1064mg dose every two months is typically for those that are stable on an oral dose of aripiprazole that is 15mg daily. For daily oral doses of 20mg or higher (such as your own), the recommended conversion is 882mg/monthly, which wouldn't reduce administration frequency relative to Abilify Maintena but could still improve symptom control and overall treatment satisfaction. If you're happy with Abilify as a treatment option, you're open to your pdoc's idea, and your insurance will cover the specific brand, ask your pdoc about Aristada. It has better pharmacokinetics than Abilify Maintena (fewer peaks and valleys in blood concentrations).
  11. You are right that, historically, the motivation of the pharmaceutical industry to develop LAI (long-acting injectable) antipsychotics was due to adherence/compliance issues. However, serendipitously discovered as well was the welcome/blissful ignorance to the antipsychotic. For many, I'm sure that even if you didn't take a pill every day, you may still feel that you are medicated, but not having to take a pill every day helps you to think less about the fact that you're taking an antipsychotic medication. And perhaps that may improve your mood overall by helping to keep your mind off of it. Does that make sense?
  12. thanks @Iceberg 😉 As far as I know without doing too much digging, sertraline is fairly selective for serotonin at 25mg to 100mg. Above 100mg, it starts to occupy the dopamine transporter as well. Generally speaking, for an SSRI, 80% SERT occupancy is necessary for antidepressant effect, but an atypical antidepressant like Trintellix only inhibits the serotonin transporter to about 55% at a dose of 10mg, yet the serotonin levels in the brain are much higher than would be expected of 55% SERT occupancy and significant antidepressant effect is achieved despite the consensus that 60% SERT occupancy is the bare minimum for antidepressant effect. So basically, you have to take that SERT occupancy together with everything else. If you achieved 80-90% SERT occupancy but also had some inhibition of DAT, then it would certainly be a different effect. Initially the increase in serotonin from SERT inhibition would cause an increase in dopamine signaling, but long-term desensitization would result in a net reduction in dopamine signaling. So adding that DAT inhibition to prop up dopamine certainly could have an effect for a small subset of patients. And the dopamine desensitization in tandem with serotonin desensitization could have a potential for a stabilizing effect in some patients with mood cycling disorders.
  13. Guess what the other name is for niacin? Nicotinic acid. Nicotinamide if it's the water-soluble form. If you're taking high levels of that, it is possible that perhaps you are building up some low levels of cotinine that make you appear as a passive smoker. What I find disturbing is that your life insurance finds a urinalysis to be acceptable proof. A blood test should be done to properly quantify the amount of cotinine in the blood and sometimes the blood tests are more accurate than the urine tests. I had to get a cotinine test as well for my employer for health insurance to get a discounted premium and that was definitely a blood test. Although you could decline the blood work and go for a cotinine mouth swab.
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