Jump to content
CrazyBoards.org

browri

Member
  • Content Count

    1,538
  • Joined

  • Last visited

About browri

  • Rank
    Member

Profile Information

  • Gender
    male
  • Location
    Pennsylvania, USA
  • Interests
    genealogy and all things tech.

Recent Profile Visitors

3,000 profile views
  1. This can definitely happen. It's just strange that it's only being noticed now. That being said of all your meds: Klonopin - Wouldn't directly reduce blood pressure or heart rate. However, by reducing your anxiety and calming you, this could indirectly reduce heart rate. Trazodone - antagonizes the alpha-1 adrenergic receptors which control heart rhythm and blood pressure. This would cause low blood pressure on standing. No significant antagonism of alpha-2 to "cut the brake lines" of the adrenergic system Risperdal - also a potent alpha-1 antagonist but unlike trazodone is also an alpha-2 antagonist, which should increase norepinephrine and dopamine output. That being said, risperidone is still known to cause orthostatic hypotension in many people. Lexapro - no impact on the adrenergic receptors, but will prolong the QT interval Trintellix 15mg - no known impact on the heart other than indirect enhancement of cardiac activity via increase in norepinephrine and dopamine signaling. Ligand for beta adrenergic receptors, but no known activity. With this all being said, your greatest culprits are trazodone and risperidone. Both medications interact greatly with the adrenergic system. Based on what I've read so far, it seems like you rely on the trazodone pretty much for sleep, which is definitely important to maintaining stability. However, it has been shown that Trintellix can improve sleep quality in those who have sleep issues related to their depression. Now that you've worked up to 15mg of Trintellix, what I would wonder is if you could start reducing the trazodone 25mg at a time every few days to a week or so until you've discontinued it or until your blood pressure and heart rate are back to better parameters.
  2. you're more likely to be anxious from the fluoxetine, quetiapine, levothyroxine, or phentermine than you are from Rexulti, which is a potent anti-adrenergic and speaking strictly to pharmacology is the most calming of all the meds in your cocktail except for maybe lithium. Do you notice the anxiety more on levothyroxine days? I see you take 150mcg only 3x a week. I take it as well but I take 25mcg every day which causes me virtually no side effects whatsoever. Phentermine will ramp up the adrenergic system and contribute to anxiety and this could be exacerbated by quetiapine's ability to inhibit the norepinephrine transporter and increase adrenergic signaling.
  3. Sorry for the delay @confused. I'll try to explain best I can, but I will say up front that I'm not a medical professional. Anyone else out there who can check me on these explanations would be appreciated. I also want to apologize in advance if this is a bit of a brain dump but I just recently started the ketogenic diet and my Depakote levels are low so I'm kind of hypomanic at the moment. The brain is a constant seesaw and it adheres to a sort of broken law of physics. Every action in the brain will elicit some sort of reaction from other neurotransmitters in the brain, but the reaction is not always equal in magnitude to the initial action and it isn't always necessary the opposite action either. You can have a chain reaction through several neurotransmitter systems that amplifies or degrades as it goes. And an increase in signaling in one system can cause an increase OR a decrease in another system. No one signaling pathway in the brain is identical to the next. In the case of selective serotonin reuptake inhibitors, they reduce the action of a protein called the serotonin transporter (otherwise abbreviated as 5HTT or SERT). Neurons will eject neurotransmitters across the synapse to each other, and it's the responsibility of the transporter proteins to return those neurotransmitters to the sending (pre-synaptic) neuron after their "mission" is complete. The old Prozac hypothesis was that people with depression either A) had lower serotonin levels, which paired with normal levels of SERT would lead to reduced serotonin signaling, or B) had normal serotonin levels but higher levels of serotonin transporter proteins leading to premature reuptake and therefore diminished signaling. A serotonin reuptake inhibitor like Prozac could therefore solve either issue. In the case of A, if the person had lower basal serotonin levels then inhibiting the transporter would encourage more of it to be in the synapse where it could (indirectly) promote healthy serotonin signaling, and in the case of B you would be actually calming an overactive protein by directly inhibiting that overactive protein. This is a tunnel vision hypothesis because it focuses on a single instrument (serotonin) in an orchestra (that also includes dopamine, norepinephrine/epinephrine/adrenaline, acetylcholine, histamine, GABA, glutamate, etc.). What researchers never took into account was that when you cause a systemic increase in synaptic serotonin levels and increase activation of central 5HT1 receptors, it causes a massive downstream release of dopamine. And due to more recent research, we know that increasing dopamine signaling will also cause a downstream increase in glutamate signaling as well. The increase of all three of these neurotransmitters at once is a highly suspect explanation for why SSRIs can initially be activating/agitating and can cause insomnia as well as other initial side effects in other bodily systems that correspond to stimulation such as increased gut motility. Now that we better understand this chain reaction, researchers are looking hard at glutamate to understand what role it has in bipolar disorder, schizophrenia, major depressive disorder, anxiety disorders, etc. More recent research shows many of these disorders do indeed have critical glutamatergic dysfunction. As a note, glutamate is an excitatory neurotransmitter. It is also the chemical opposite of GABA, which is the neurotransmitter key to central nervous system depression (don't think mood, think sedation/calm). This is where alcohol works. Benzos. Date rape drugs like GHB and Rohypnol (which most people don't realize is otherwise known as flunitrazepam). So we believe now that in the case of bipolar disorder, the mood swings could be due to a seesaw effect that occurs between serotonin<-->dopamine and between glutamate<-->GABA. In schizophrenia, there would generally be increased glutamate and dopamine signaling leading to psychosis. In general major depressive disorder, glutamate may be underactive, but there may just be a version of major depressive disorder with anxious distress that involves OVER-active glutamate signaling. The confusion never ends.......or rather the spectrum never does. But that's what we need to realize. This is why one medication works for a handful of people and not for one other person. Major depressive disorder and bipolar disorder and schizoaffective disorder are truly just categories that we put many people in, even though many of them are nothing alike. Because of how many genes we have, we now know there could be tens or hundreds of variations of each disorder that is better addressed one way than for the next person. FINALLY, to get to the meat of your original question, D1 receptors are pretty central (pre-frontal cortex). They are the site of the therapeutic effects of stimulants, which cause neurons to expel dopamine into the synapse. For people with ADHD, increased binding/activity at D1 receptors has a stimulating effect, and we can hypothesize that downstream increase in glutamate signaling must have something to do with it. The idea with Caplyta (lumateperone) is that blocking D1 with moderate affinity will reduce downstream glutamate signaling without harming executive function, concentration/focus, etc. (working like the "opposite" of a stimulant) However, this reduction in glutamate activity can have positive effects on bipolar disorder and schizophrenia by generally reducing excitability of neurotransmitter systems. Additionally, because glutamate <--> GABA work on a "seesaw" when you reduce glutamate signaling, glutamate is more readily metabolized inside neurons into GABA, which can be used to further calm the brain (bit of a snowball effect). What I won't go into in this post is receptor sensitivity and the process of desensitization and resensitization. Easily doubles the length of this post.
  4. The manufacturer claims that lumateperone modulates glutamate via it's action on D1.
  5. Other than Paxil, your best choices are Celexa and Lexapro (citalopram & escitalopram), although Lexapro is preferable and more effective for most. Interestingly enough, we have coined this class of supposedly SELECTIVE serotonin reuptake inhibitors meaning they supposedly only do that or that's how they exert their effect. However, Lexapro (escitalopram) is the MOST selective of the SSRIs in that other than the serotonin transporter (SERT), it doesn't bind to much else. Paxil (paroxetine) on the other hand as a "SSRI" is also a mild norepinephrine reuptake inhibitor, anticholinergic, and anti-alpha-adrenergic. Even Prozac (fluoxetine) is not selective. It also dramatically increases norepinephrine and dopamine signaling by blocking the 5HT2C receptor and also having some mild norepinephrine reuptake inhibition. This could be why it's stimulating for some at higher doses.
  6. That doesn't surprise me. Valproic acid free base is 100% immediate release whereas divalproex is partially sodium-bound thus improving pharmacokinetics and extending half-life.
  7. Sorry it didn't work out for you. If you decide to try it again, start at 0.25mg for a few weeks before increasing.
  8. Or you're a smaller guy. I'm 5'11" and 220lbs. Valproate is dosed by weight.
  9. Holy cow, you take 1000mg of Depakote but VPA still clocks in at 81 ug/mL ? Or is that level from when you were at 1500mg of Depakote? I mean I take 1000mg and I only generally get a level in the high 30s to mid 40s.
  10. If he already gave you the okay, then there's no reason to check with him. Just remember to bring it up at the next appointment, and no harm, no foul. I'm glad to hear that the decreased dose is helping. Some people do better on 100mg or 150mg. The higher dose of 200mg isn't always necessary, but it does provide the most optimal mood control. If you start to notice any returning depression, then increasing again to 200mg should help.
  11. Check this out. Take the time to wade through the scientific lingo. There's good stuff here. https://www.ecnp.eu/presentationpdfs/71/P.1.g.038.pdf
  12. More than likely you would actually need less and not more in this case. Doses of lumateperone as low as 7mg were tested, with the 42mg dose being the approved dose because it was the most efficacious for schizophrenia. However, the 7mg dose was found to have quite some benefit in the realm of sleep regulation in MDD as well as agitation related to Alzheimer's. That dose is advantageous because it completely saturates the 5HT2A receptor, making it a good adjunct for MDD to reduce agitation and anxiety as well as improve circadian rhythm. This dose also has far less effect on the D2 receptor which is advantageous for geriatric use where inhibition of dopamine signaling may not be desirable or safe. The 42mg dose is a high enough dose to achieve non-inferior antipsychotic efficacy due to its 33 nM affinity for D2 and 41 nM affinity for D1. The advantage that lumateperone has is the additional antagonism of 5HT2A, the inhibition of the serotonin transporter, and even a little bit of brakes on the adrenergic system which should be beneficial for a wide variety of other disorders.
  13. Actually the schizophrenia target dose is 3mg with a max of 4mg as opposed to MDD at a target of 2mg and max of 3mg. Going to 3mg in MDD may be beneficial for some but not for most. 3mg and 4mg are generally the schizophrenia doses. Actually I just felt all around incapacitated starting on 0.5mg. I had to decrease after 2 weeks to 0.25mg, do that for 4 weeks, then increase again to 0.5mg. do that for 4-6 weeks then increase to 1mg.
  14. Actually the real calming and antidepressant oomph is at the lower doses. You go to the higher doses just to get more stimulation if the lower doses aren't enough. I personally find 1mg to be enough. Keeping my dose low, that's the highest I've ever had to go.
×
×
  • Create New...