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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. Make sure anything you do is done with your doctor's approval. The concern with lamotrigine is decreasing too fast and precipitating seizures, although it looks like you did take it slowly which is good at least. The likelihood any mind blanks were coming from lamotrigine is pretty high. On 200mg myself, I had plenty of issues with word recall specifically. It's possible that SSRIs and SNRIs can cause true restlessness for some people. I mentioned in a previous post that imipramine has anticholinergic effects and this may be helping you to tolerate the SRI and NRI effects. And yes, with quetiapine, starting around 150mg to 200mg, there is a norepinephrine stimulating effect that picks up and becomes stronger as you get to 300mg. From there, it generally doesn't increase considerably and is drowned out by blockade of adrenergic receptors.As I said previously, between that and the alpha-2 antagonism, it's liable to possibly make you feel "nervous" even though your general anxiety level may be lower. Said another way, perhaps you have less anxiety "spiking" during the day and a more steady low level nervousness that never goes away. Nervousness is a known side effect of quetiapine, albeit less common unless your sensitive to those kinds of things. Hey if you're taking time off work, even better. Now is definitely the time to figure this stuff out before you have to get back to it. I hate doing med changes and having to work at the same time. Sometimes it's fine, but sometimes it's just miserable. Nope I just read more than I probably should. But my pdoc has told me before that he thinks I may have missed my calling soooooooo.......
  2. This is really hard to put a finger on. I didn't realize you were on doses of quetiapine and lamotrigine that high. That speaks more to a treatment for bipolar depression than anything, and the fact that any sort of serotonin reuptake inhibitor makes you anxious (including the imipramine that you're currently trying) also makes me think serotonin antagonists are actually going to be your drug of choice. However, what's notable with quetiapine at that dose is the prominent norepinephrine reuptake inhibition (NRI). It's possible that this may make you feel nervous during the day. With the NRI effect combined with antagonism of pre-synaptic alpha-2 adrenergic receptors, there would be even further adrenergic output. This can make you feel a persistent fight-or-flight response, or in constant state of stress in a manner of speaking. Believe it or not, my recommendation would be to talk to your pdoc about reducing your quetiapine and lamotrigine. Going down on quetiapine may make you feel less "revved up", thus less need for lorazepam during the day. The lower dose may also make it easier to sleep without zopiclone or lower zopiclone dose / less frequency. Also, most of the data shows that lamotrigine doesn't usually provide additional benefit above 200mg. It may be worth talking to your pdoc about 100mg twice a day, or 50mg in the AM and 150mg in the PM. From there, if your anxiety has improved but you're still depressed, it may be worth talking to your pdoc about adding a little bupropion. I see from your signature that one isn't listed as a previous trial. Although you're in the U.K. and I believe that the Royal College of Psychiatrists in London has yet to accept/appreciate bupropion's antidepressant effects, preferring instead to use it only for smoking cessation. However, in the U.S. bupropion/quetiapine is a popular combo due to bupropion's low propensity for causing manic switch. Its norepinephrine-dopamine preferring profile also complements quetiapine's pharmacodynamics. This combination may be dicey because there's a 50/50 chance it can bring your anxiety back or make it worse, but there's also a chance it could reduce your anxiety further. Would just be curious what it would do for your sleep.
  3. Ah okay. I didn't realize that Seroquel was a daily medication for you. So what are your total daily doses of everything? Yeah try not to expect side effects, because then they will definitely happen. You know that. Yes it looks like they use the same Genecept assay that's used by one of the major companies over here in the States. Most importantly regarding the test is that it probably won't reliably tell you what WILL work for you but rather what WON'T so that the merry go round of medications is less of a process of elimination. I'd be curious then if escitalopram may work for you. It's arguably more potent than citalopram and better for anxiety too in my experience. The fact that you tolerated mirtazapine for so long but can't get higher than 75mg on Effexor and think Cymbalta is too strong tells me that energizing antidepressants aren't what you're looking for. That rules out a good amount of them but leaves you with citalopram, escitalopram, and paroxetine. The remaining ones: sertraline, fluoxetine, duloxetine, venlafaxine, et. al. would just be stimulating for you. In the U.K. vortioxetine is called Brintellix. It should be available to you now that you've tried several different antidepressant options.
  4. Not likely. You'll most likely adjust if you were able to with your previous medications. If you weren't able to tolerate SSRIs or SNRIs though, the prognosis with tricyclic antidepressants isn't great. Although the improved efficacy may override that. Only time will tell. So this tells me that maybe the agitation is serotonergic in nature. I imagine you felt this way starting up on SSRIs and SNRIs as well? Initially, serotonergic activation from serotonin reuptake inhibition can cause some pretty serious agitation, and it's fairly normal to control SRI startup effects with benzodiazepines like Ativan (lorazepam). However, the fact that quetiapine is what did it for you tells me that blunting the effects at serotonin receptors helps to calm things for you. So my next question would be whether or not you could get in the habit of taking quetiapine at bedtime every night instead of taking it as a PRN ("as needed"). Not likely. Lamotrigine is a glutamate reducing agent, but in some ways it can increase glutamate output in some areas. And this is why lamotrigine can be activating in the beginning. Imipramine may have a similar effect but it's downstream of its effects on serotonin. Inhibit the serotonin transporter, serotonin builds up in the synapse, 5HT1A receptors became hyper-activated, leading to increases in downstream release of dopamine, further downstream release of glutamate, which then REDUCES dopamine release. Checks and balances in the brain are weird. So now that I think about it, because lamotrigine can in some ways potentiate glutamate signaling, it's possible I suppose that the initial imipramine period may in some ways feel similar to starting up on lamotrigine, or lamotrigine may be making you more sensitive to the startup effects of SRIs. Either way, a benzodiazepine should be able to control it, but more may be required, and round the clock coverage may be required as well. So for me, my pdoc would prescribe clonazepam 0.5mg tablets. Then he would have me take half a tablet in the morning, half a tablet around noon, and a whole tablet around 6PM. That would give me 1mg in a day, and clonazepam has such a long half-life that if you take it continuously, after a few days, the sedation goes away and you just generally feel quite calm. Then you slowly reduce your dose. Perhaps first by eliminating the noon dose, then reducing the evening dose to half a tablet, then eliminating the morning dose, then after several days eliminate the evening dose altogether. Still, the fact that quetiapine was more effective makes me wonder if you should just continue with daily lamotrigine/imipramine/quetiapine, then you probably wouldn't need the lorazepam during the day or the zopiclone at night because quetiapine can handle that. Better not to use benzo's or Z-drugs long term if you can help it. Oh good! I always forget that those tests aren't as readily available overseas. Glad you found one though! What's it called?
  5. Do you think you can tolerate the effects in the short term? Highly likely that some of those side effects will go away or become less intense as you adjust to the increase in dosage. Have you ever had gene testing done? Like GeneSight or any of those other psych genetic panels that one can do? It may provide guidance as to whether or not reuptake inhibition is something you definitely want to stay away from. Does 25mg of Seroquel help when 1.5mg of Ativan doesn't?
  6. Well my thinking is that before you were having 1000mg at night which may cause some grogginess for sure in the morning if it's the 12-hour formulation. I take 1250mg of the 24-hour formulation all at night and I still sometimes feel groggy in the morning if I take it too late. Try to take it at like 7-8PM. Yeah valproate is horrendous on the stomach. Immediate release does exist but it has to be taken 3x/day, which is obviously inconvenient. That's why they came up with the 24-hour tablets. Improved compliance and moved most of the pill digestion to the intestines instead of the stomach. Neither have I 😅
  7. That's great! With tricyclics, as long as side effects are tolerable, they are far more effective generally than newer meds for many people because their treatment effects are so comprehensive
  8. I'm thinking these are the delayed release 12-hour tablets. Sodium valproate too because they don't use divalproex outside the U.S. really.
  9. So you were previously taking 1000mg in the evening and 500mg in the morning. Now 500mg morning and night?? Or do I have that wrong? Also, the tablets you are taking, are they Epilim/Depakote (delayed release 12-hour) or Epilim Chrono / Depakote ER (extended release 24-hour)? Does your prescription bottle actually say Epilim, sodium valproate, divalproex sodium, valproate semisodium? Just curious.
  10. So I'm gonna take a stab at this one. Imipramine is a unique tricyclic in that it is very effective for childhood nocturnal enuresis ("wetting the bed"). It does this by blocking muscarinic acetylcholine receptors, which can also adversely affect cognition. This may be what you are experiencing, and it is one domain of side effects that caused doctors to switch over to using SSRIs and SNRIs instead because of their selectivity.
  11. Indeed. Nortriptyline is a metabolite of amitriptyline. The parent drug is preferential to the serotonin transporter (SERT) over the norepinephrine transporter (NET) or the dopamine transporter (DAT), whereas the child prefers the opposite. This is why nortriptyline is often used as an augmenting agent. Additionally, while nortriptyline has clinically negligible effects on DAT, its potent inhibition of NET in the pre-frontal cortex would indirectly ramp up dopamine signaling as well, making nortriptyline a makeshift NDRI. Importantly though are nortriptyline's 5HT2A and 5HT2C antagonist properties, both of which can lead to additional norepinephrine and dopamine release. Compound this with NET inhibition and you've again got a really robust effect. Nortriptyline seems to have some evidence in smoking cessation as well. Again though, like other tricyclics, it has fairly strong anticholinergic effects: Because nortriptyline is more of an NRI, you can mix it with some MAOIs if it's done carefully, but it should be a last resort. More than likely the most robust combo would be with either selegiline or tranylcypromine as they are preferential for inhibition of MAO-B, which is responsible for the breakdown of norepinephrine and dopamine predominantly, as opposed to MAO-A, which prefers serotonin oxidation. The concern of course with combining an MAOI and any kind of serotonin reuptake inhibitor is serotonin syndrome. Nortriptyline's affinity for the SERT is lower, but still considerable. If you start both medications on their lowest doses and increase either medication in tiny increments, only changing one med at a time and also giving plenty of time between dose changes, but it can be done.
  12. The most important takeaway I think is that while stimulants are stimulants, they can be stabilizing for a lot of people. So yeah, when you go off of them, for the first 2 weeks you feel miserable. But after that, once your brain really starts getting used to operating without stimulants again, many find that episodic, brief/intermittent moments of depression are less common, that they are generally less depressed. However, it's possible there may be more mood instability. So less depressed, and less stable. This is also why doctors use Wellbutrin as a mood stabilizer in some patients.
  13. Hahah don't worry and don't feel dumb. We talk like we know what we're talking about, but we're not doctors. And even if we were, we don't truly understand enough of how the brain works. Which SSRIs have you tried and can you remember if there were any side effects that were specific to one med or worse on one than on the others? This is notably interesting... ....considering that SNRIs seem to help a lot, I would expect that Wellbutrin would have a similar positive effect. The fact that it didn't work indicates that you do need some sort of serotonergic intervention, but perhaps inhibition of serotonin reuptake isn't the path to take in this case. I find it laughable that doctors would bother trying Effexor if they aren't willing to go to 300mg. You CAN go to 450mg, but that's heroic. You should AT LEAST be willing to go to 300mg though if the patient is tolerating 225mg. There's a lot of evidence that in some people, the more potent pro-dopaminergic effects of Effexor aren't seen until the top of the dose range. At what point did you add Lamictal, and would you say it was an improvement in your treatment? I mention this because Lamictal is a glutamate reducing agent although I prefer to say it modulates because it can promote glutamate signaling in some ways. Glutamate is an excitatory neurotransmitter in the brain, and it's believed that Lamictal's effect on glutamate can have positive impacts on depressive states and mood swings. This is why they use it in bipolar disorder, but they do find that there's a subset of those with MDD that experience depression with anxious distress who respond well to medications that calm glutamate signaling (or we just give them benzos to increase GABA signaling, which is just an indirect way of doing the same thing). If you have major depressive disorder, there is the option of reducing the Lamictal to 100mg to see if there is some improvement in mood. Alternatively, you could increase it because there is often additional benefit seen all the way to 200mg. So I can think of a couple possibilities here. If you're seeing a new pdoc shortly....someone who is an experienced psychiatrist, then you should really start by optimizing doses of existing medications as far as you can tolerate them. If the issue with Effexor is that it seems to have pooped out but there aren't any side effects, then it should be increased to 300mg. Additionally, if you feel that Lamictal has helped you, it should also probably be pushed to 200mg before deciding to change medications to something else. Effexor is a very effective antidepressant in a lot of cases that don't respond to other first-line agents. Considering that it has historically been the one thing that has worked for you, perhaps you augment it with something else besides Lamictal. My recommendation in this case would be Remeron because the Effexor+Remeron combo is referred to as "California Rocket Fuel" as it gained popularity among psychiatrists in California and elsewhere along the west coast. Remeron on its own is generally regarded as a sedating medication until you get to the higher doses, but combined with Effexor it can supposedly be quite stimulating for many and can breathe new life into Effexor if the patient stops responding to it. This can also have a calming effect on anxiety. So it's possible that you may be able to rely on Klonopin less. And Remeron would be taken at bedtime. It's sedating enough at low to moderate doses that you may not need Ambien anymore either. By contrast, if you felt that you noticed a considerable improvement when adding Lamictal, I would say consider swapping Effexor for Trintellix. I'm currently taking it and find it to be continuously effective and it hasn't caused the activating/agitating side effects that SSRIs and SNRIs cause me except maybe at the highest dose. Additionally, if you didn't respond well to SSRIs due to side effects, it's possible that you may experience some of those problems on Trintellix at the highest dose (20mg). However, I personally rarely ever go to that dose. I find it to be too activating and unnecessary. 15mg is usually enough even in the deep of Winter and despite being really close to 20mg seems to be more tolerable. 5mg and 10mg are a cake walk when you adjust to them. I personally find Rexulti very calming and helps with sleep. It's an atypical antipsychotic approved as an add-on to an antidepressant for MDD like Abilify and Seroquel. It's been far better for me than either of them though. You could possibly swap Lamictal for Rexulti, and over time you may find that your anxiety gets better as well as sleep, thus necessitating less Klonopin and Ambien like in #2. I'd be curious to know other medications you've tried and what your experience was like with them.
  14. Yeah I tried going without Vyvanse. Managed to get past the first 2 weeks, which were hellish, like you describe. However, at about the 1 month point I just decided that my focus was far better on stimulants than off them. In those few weeks, I forgot so many important things that were also simple things. It was a frustrating few weeks. So I get the feeling. However, if you make it to a month with no stimulants, you'll find that sometimes you do feel less depressed. Generally though if you're bipolar, stimulants can be stabilizing. So while I felt less depressed at times, when I did feel depressed, it was worse off stimulants than on stimulants, naturally. And I was more likely to oscillate between a happy, content mood and a dysphoric one.
  15. @the maze runner well I'm sure you know that methylphenidate and valproate are two completely different compounds and work very differently in the brain and even feel quite different to the individual, they can both mediate similar downstream changes. For example, bupropion (Wellbutrin) is regarded as a much more stimulating antidepressant and is structurally related to amphetamines and other stimulants like methylphenidate. It is a norepinephine-dopamine reuptake inhibitor like stimulants and a modest releasing agent of these neurotransmitters as well. This causes desensitization of the dopamine system and is inherently stabilizing as a result. The same concept is applied with serotonergic antidepressants and also explains why they can make things worse in the beginning (insomnia, increased anxiety, irritability). Serotonergic activation can mediate many of our mental illnesses. So ramping that up and desensitizing the brain to that signaling can quiet the downstream thought processes. Where stimulants and bupropion stabilize the dopamine system via increased dopamine signaling and desensitization much like serotonergic antidepressants, valproate on the other hand actually attempts to directly calm the brain on various different levels. 1. It inhibits GABA transaminase and succinate-semialdehyde dehydrogenase which degrade GABA in the brain. Because GABA is the main calming/"depressant" neurotransmitter in the brain, this causes an increase in basal GABA levels. 2. It modulates but generally increases the activity of glutamate dehydrogenase, which would catalyze the conversion of glutamate back into GABA. Because glutamate is a primary excitatory neurotransmitter in the brain, this has a direct calming effect. Glutamate is implicated in some depressive disorders with marked anxious distress as well as bipolar disorder. By inhibiting GABA's breakdown in #1 and inducing glutamate's conversion into GABA here, further increases in basal GABA levels are realized. 3. It induces monoamine oxidase A which is chiefly responsible for the breakdown of monoamines like serotonin and to a lesser extent norepinephrine and dopamine. This results in lower serotonin signaling. 4. Via some mechanism, it reduces catecholamine synthesis (i.e. norepinephrine and dopamine) The net results though is that valproate administration can actually INCREASE norepinephrine and dopamine concentrations in certain brain areas and decrease it in others. While these two medications are miles apart, perhaps for you they both mediate similar changes in your brain that make you feel better. Another possibility is that after continued methylphenidate treatment you may be experiencing a bit of neurotransmitter depletion. This is something that everyone who takes stimulants goes through every day. They start the day with a ramp up in virtually all neurotransmitters, then they plummet as the day continues into the afternoon and the stimulant wears off. You can tell because psychotropic-induced dilation of the pupils for most people on stimulants is the most pronounced in the afternoon. But what happened if that neurotransmitter depletion persisted? That's basically the first 2-4 weeks after you stop taking stimulants. Your brains neurotransmitter levels adjusting to the change. The only difference is that with divalproex on-board, while your serotonin and dopamine levels are in the dumps and you're feeling helpless and angry, valproate is increasing GABA levels and soothing the brain much in the same way that alcohol would actually.
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