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About browri

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    Pennsylvania, USA
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    genealogy and all things tech.

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  1. 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.
  2. 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.
  3. Yeah when I first get back on Klonopin, I sometimes feel grogginess for the first 3-5 days. After that, I usually do okay. But it can linger for up to two weeks.
  4. This sounds like a good plan of attack to me. I'm not surprised your pdoc would prefer you on Caplyta + long-term benzo if needed over Zyprexa because the metabolic safety issues with Zyprexa are a serious concern, whereas Caplyta so far seems to show very little metabolic impact, at least when compared to Risperdal. Theoretically you should be less likely to develop tolerance to Klonopin with consistent dosing as well unlike Valium which does have tolerance issues.
  5. Agreed. If certain symptoms are manageable for the time-being, address the more severe ones first. There's always the option of changing the citalopram later too, but you start by adding the risperidone because, generally speaking, OCD symptoms can be distressing and further exacerbate existing depression. Unfortunately, our pdocs only see us for so long each visit though, and they can try to make a clinical judgement call based on what they see right in front of them, but they do still rely on us to tell them what distresses us most. In my mind, it makes more sense to augment first just because it has a higher chance of success at resolving all reported issues instead of an AD switch strategy which may only resolve one issue. This of course is an option as well. If you're on 40mg citalopram, it wouldn't hurt to talk to your doctor about at least trying escitalopram 10mg to see if there's any difference. There may not be, but citalopram is a racemic mixture where the R- enantiomer isn't completely silent. It actually antagonizes some of the effects of the S- enantiomer. So where escitalopram could be more effective, ar-citalopram, makes it less effective. Some people report improvements converting from citalopram to escitalopram. And there's room for dose increases too. Some say that citalopram is half as potent, but with the added antagonist effect of the R-enantiomer, 40mg citalopram doesn't necessarily equal 20mg escitalopram. Citalopram is probably more like a third as potent where 20mg, 40mg, and 60mg citalopram translate more to 5mg, 10mg, 20mg escitalopram, respectively. Except they don't prescribe citalopram up to 60mg anymore due to prolonged QT interval which is apparently less pronounced with escitalopram?
  6. So if your goal is to switch to a benzo regimen that is a little less "moreish" (in that you want more and can barely wait for your next dose), you truly would want to consider clonazepam (Klonopin) around the clock. It has one of the longest half-life of the benzos leaving pretty much only diazepam and flurazepam being longer. However, diazepam is broken down into several metabolites and definitely falls into the "moreish" category. My pdoc loves clonazepam for its long half-life and lower propensity to develop a tolerance than something like diazepam. When I'm more panicky than usual, my pdoc has me do 0.25mg with my morning meds, 0.25mg somewhere between noon and 2PM, and then another 0.5mg at bedtime for a total of 1mg in the day. I do sometimes find myself anxiously awaiting the noon dose sometimes, but I don't feel panicky in the mornings and by the afternoon I'm usually not jonesing for the evening dose.
  7. Risperidone should reach steady state in the blood stream around 4.5 days after daily administration. But there are changes in receptor sensitivity and expression that can occur for the 2-4 weeks beyond that steady state being reached. @Iceberg @CeremonyNewOrder My pdoc thinks of this like a game of chess. What's the next move? In the case of the OP @OCDme, the pdoc has noticed that citalopram 40mg isn't working the way it used to, so you either switch or augment. However, the patient also reports issues with rumination and obsessive thoughts. Those issues likely wouldn't be addressed with a switch to a different AD (like going from citalopram 40mg to escitalopram 20mg or fluoxetine 40mg). However, you could address both rumination and antidepressant poop-out with an augmenting agent like an atypical antipsychotic. Of course when thinking about augmenting an AD it's natural to gravitate towards aripiprazole. However, the patient reports having issues settling their thoughts, and aripiprazole is liable to push them in the opposite direction. Risperidone and quetiapine (Risperdal and Seroquel, respectively) are the only two atypical antipsychotics that are "silent" dopamine antagonists and can settle the thoughts enough to address obsessive rumination. They both seem to have the most evidence in treating OCD when high dose serotonin reuptake inhibitors aren't an option (like clomipramine 120mg or fluoxetine 80mg) +1 It is normal for the brain to adjust over time, even to the medications that we feed it. Think about it this way. When you work out to build muscle mass, you oftentimes need to rotate between different kinds of exercises of a specific muscle group in order to get continuous results or your muscle growth will plateau. This is because the muscles adjust over time to being worked out in a certain way. The brain isn't so different.
  8. What you're describing sounds more like a combination of Zyprexa withdrawal and Caplyta startup effects at the same time actually. Most commonly for the "-pines" like olanzapine and clozapine is the issue of cholinergic and adrenergic rebound upon discontinuation. Olanzapine is a potent anticholinergic, which has calming properties. It can also reduce gut motility. Coming off an anticholinergic not to mention an antiserotonergic (serotonin is also responsible for gut motility) could explain the diarrhea. Olanzapine potently blocks alpha adrenergic receptors (both auto-receptors and hetero-receptors). So you might be experiencing some adrenergic sensitivity that may come across like an overly sensitive fight-or-flight response. Nausea is listed is one of the most common side effects of Caplyta next to somnolence. I've never taken Caplyta but have heard from one other person that the nausea starting up on Caplyta was no joke but they adjusted to it. Intuniv (guanfacine) is an alpha-2 receptor agonist. The alpha-2 recepors act as auto-receptors for norepinephrine and epinephrine/adrenaline. When activated, they slow adrenergic output, when blocked or inactivated, they increase output. It's a feedback loop. Olanzapine has been blocking those receptors thus increasing the amount of signaling norepinephrine. Olanzapine also blocks alpha-1 receptors, so you don't feel that increase in adrenergic flow. Now all the stops are pulled out and your adrenergic system is responding in a sensitive way. Guanfacine will work by activating alpha-2 receptors to reduce norepinephrine output which should help to calm the over activated alpha-1 receptors. To answer your second question, yes clonidine is generally regarded as somewhat more potent than guanfacine and works in the same way. Klonopin is more potent by dose than Valium, but Valium is probably broader spectrum. Can't say for certain though. 10mg of diazepam is roughly equivalent to 0.5mg of clonazepam. When I'm having anxiety/activation like what you're describing, I usually need 1mg clonazepam. Caplyta supposedly takes 5 days to reach steady state. And you can reasonably expect adjustment for 2 weeks beyond that point, and further adjustment with each decrease of Zyprexa. Remember that Zyprexa and Caplyta work very differently though, and it's possible you may be incompatible. Just be sure you give it enough time and be patient. Keep your pdoc in the loop. If he gave you the okay to manage these breakthrough symptoms with Valium and Intuniv then definitely do it. If there's a chance that Caplyta will work for you, it can apparently REALLY work.
  9. I was on it for 6-8 months. And yes, oh so calming. I tried Latuda, Saphris, Fanapt, Abilify, Rexulti, loxapine, Zyprexa, probably missing some. My favorites were Zyprexa or loxapine, but loxapine I had to push into akathisia dose space for full symptom control. Zyprexa made my weight balloon and my lipids and blood glucose go out of control after just 6 months on 5mg. If it didn't make me so metabolically dysfunctional, I might have actually been able to live on it. However, after Zyprexa and loxapine, I found Rexulti and it has provided a similar calm paired with a cool stimulation that I just can't beat and it doesn't cause as much weigh gain as Zyprexa either. That being said, Rexulti is brand only right now and if I were to lose my insurance I PROMISE YOU I will be back on Zyprexa stat because it's the only thing that manages my anxiety, mania, and depression all in one pill.
  10. General sentiment is that for bipolar disorder, lamotrigine blood levels aren't as relevant to treatment response as those blood levels would be when treating epilepsy. Meaning if you have seizures you want to make sure you have steady levels throughout the day to ensure proper seizure control. However, for bipolar disorder, steady levels throughout the day don't seem to be necessary for mood control for most people unlike valproate or lithium. Speaking of valproate though, there are scenarios where you could be prescribed valproate and lamotrigine, at which point a doctor would likely always test the lamotrigine level. I was on the combo briefly, and because those two meds can do unpredictable things to each other's metabolism, it's best to keep an eye on the level. Valproate can increase lamotrigine's level, but lamotrigine can either increase or decrease valproate. Depends on the person. When you have interactions like that, then you test lamotrigine levels. Otherwise, you only test them if you have epilepsy and you're on higher dose lamotrigine (>200mg).
  11. Lamotrigine is predominantly a glutamate-reducing agent. But it has been shown to increase glutamate signaling in some ways such as very weak 5HT3 antagonism. There is a fringe group of patients whose depression is glutamatergic in nature versus serotonergic. Those patients typically respond to lamotrigine over typical antidepressants that focus on increasing serotonin signaling. You wouldn't want to take lamotrigine with ketamine infusions because lamotrigine would interfere with that subsequent glutamate outflow caused by ketamine's NMDA receptor antagonism. Just a guess really. But you wouldn't want to block NMDA glutamate receptors (ketamine) AND reduce glutamate output (lamotrigine) even if either on their own could result in improvements in glutamate signaling.
  12. I can describe a few different pieces to a puzzle with trillions of pieces. What I know is that clonazepam is depressogenic. It doesn't matter that it may reduce anxiety and thus make someone more at ease and potentially LESS depressed. If I'm having anxiety, I take it regularly. After about 2-3 weeks, I start to feel depressed. The point is that the way clonazepam works is by depressing the brain via GABA-A receptors, GABA being the chief inhibitory neurotransmitter in the brain. Glutamate, on the other hand, is the chief excitatory neurotransmitter in the brain. The brain tends to release more of it when other receptor systems are activated, and activation of the glutamatergic system subsequently inhibits the release of neurotransmitters, creating a feedback loop. Glutamate is GABA's opposite. Like day and night. When you take amphetamine, it activates TAAR1 receptors which cause neurotransmitter efflux. Activation of central dopamine receptors leads to increased release of glutamate, which in turn slows down the release of dopamine. So if you block the glutamate receptors (NMDA receptors, specifically), what happens? You've just cut the brake line, leading to a complete disinhibition of the brain and subsequently release of neurotransmitters, particularly dopamine. Ketamine, furthermore, is not just an NMDA receptor blocker, but interacts with many other receptor systems like the sigma receptors and opioid receptors. It does even have some affinity for dopamine receptors as well. Glutamate, while excitatory and an important part of the nervous system, is toxic in high levels and not modulated properly. Inhibiting NMDA receptors with a substance like ketamine would not only disinhibit the brain and encourage nerve growth, but because the brain detects no glutamate binding to NMDA receptors, it will increase glutamate output. While glutamate can be neurotoxic in high levels, when modulated correctly, it can actually have positive effects on depression. This is part of the reason why some people respond to no antidepressants, but they try lamotrigine or ketamine and it's a game-changer. Those are both glutamatergic agents meant to increase glutamate output, dampen glutamate signaling (simultaneously), and subsequently activate numerous other neurotransmitter systems both directly and indirectly. Additionally, this may be why vortioxetine may be more effective for some people than other antidepressants. It potently antagonizes 5HT3 receptors which increase glutamate output as well. The problem with clonazepam is that as an activator of the GABA inhibitory system. It could potentially dampen the positive response from ketamine. While ketamine blocking NMDA receptors may help the brain to reset, any neurotransmitter outflow downstream of ketamine would be dampened by clonazepam. So when the nurse says it's "not that big a deal", what they mean to say is for ketamine, you ideally want to do it with as clear a head as possible. The goal with ketamine infusions is to hopefully reduce polypharmacy. You may even find that ketamine infusions make it easier to go without clonazepam, but make sure you always discuss these things with your pdoc.
  13. I can definitely +1 the anxiety feeling of both starting AND stopping Lamictal. Going up is always a challenge on the first few dose hops. I felt like 25mg and 50mg were difficult jumps. 100mg wasn't so bad, and beyond that the dose changes were more tolerable. However, yes the Lamictal titration is rocky. If it's going to work for you though, it will likely do so with little to no side effects. The only side effect I had from it after the titration period that didn't really go away with time was issues with word recall. Definitely should continue up if you can handle it. However, if you haven't tried it yet and you don't plan on having any children, Depakote is actually a wonderful option. More tolerable than lithium in my experience. Lithium made me feel downright ill. Depakote makes me feel like I can sit still for a moment and be calm. It's really nice.
  14. To answer your question directly, I believe the two that you're most likely to be prescribed by a doctor would be either nortriptyline (metabolite of amitriptyline) or desipramine (metabolite of imipramine). Both or far more noradrenergic than their parent compounds, and they theoretically should be stimulating where the parent compounds would probably be sedating. The other one which you probably wouldn't be able to get prescribed is protriptyline, which is more of an NDRI like bupropion. Your signature indicates schizoaffective, bipolar type. You're on 1500mg lithium and 1250mg valproate, which will cause a fair bit of sedation. Coming off of dextroamphetamine won't help either. However, your saving grace is that you are reducing clozapine and increasing aripiprazole, which should be more stimulating. Not to mention clozapine on its own can be quite sedating for some people. If you can tolerate aripiprazole no problem, then I would say to wait until you've completely titrated across to aripiprazole and you've been on your target dose of aripiprazole for at least 3 weeks and off dextroamphetamine for 2 weeks before making a decision of whether an antidepressant is needed.
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