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Effexor at different doses: 75mg-150mg-225mg??


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I've taken Venlafaxine in the past, but can folks here describe how different doses affected you? (i.e. different side effects at each dose?)  Would you recommend ONLY brand (or generic OK too?). I need to increase, but I'm afraid of the "numb zombie effect" happening at higher doses.....

Currently at 75mg, and feeling only typical Serotonergic effects (calm, drowsiness, lethargy, spaciness, dry mouth, blurry vision)

From what I read at 150mg, it primarily affects Norepinephrine (giving to a more energizing/possibly anxious feeling?) And at 225mg, it starts working on increasing Dopamine (I don't know how much in comparison to serotonin & NE ?)

Also, I want to switch to XR due to the longer half-life (and smoother withdrawal). Is the XR all-day coverage? (The instant can give brain zaps sometimes after wearing off)

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2 hours ago, Blahblah said:

I've taken Venlafaxine in the past, but can folks here describe how different doses affected you? (i.e. different side effects at each dose?)  Would you recommend ONLY brand (or generic OK too?). I need to increase, but I'm afraid of the "numb zombie effect" happening at higher doses.....

Currently at 75mg, and feeling only typical Serotonergic effects (calm, drowsiness, lethargy, spaciness, dry mouth, blurry vision)

From what I read at 150mg, it primarily affects Norepinephrine (giving to a more energizing/possibly anxious feeling?) And at 225mg, it starts working on increasing Dopamine (I don't know how much in comparison to serotonin & NE ?)

Also, I want to switch to XR due to the longer half-life (and smoother withdrawal). Is the XR all-day coverage? (The instant can give brain zaps sometimes after wearing off)

If I remember correctly, I think that at 75mg, venlafaxine is basically an SSRI.......I am not certain how high dose needs go, to hit Norepinephrine, or Dopamine......Here's 2 CB members that might have more knowledge about that:

@Iceberg   @browri

Edited by CrazyRedhead
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3 hours ago, Blahblah said:

I've taken Venlafaxine in the past, but can folks here describe how different doses affected you? (i.e. different side effects at each dose?)  Would you recommend ONLY brand (or generic OK too?). I need to increase, but I'm afraid of the "numb zombie effect" happening at higher doses.....

Currently at 75mg, and feeling only typical Serotonergic effects (calm, drowsiness, lethargy, spaciness, dry mouth, blurry vision)

From what I read at 150mg, it primarily affects Norepinephrine (giving to a more energizing/possibly anxious feeling?) And at 225mg, it starts working on increasing Dopamine (I don't know how much in comparison to serotonin & NE ?)

Also, I want to switch to XR due to the longer half-life (and smoother withdrawal). Is the XR all-day coverage? (The instant can give brain zaps sometimes after wearing off)

Yes, the dosage increases do seem to target specific neurotransmitter areas, though I'm not sure if increasing the dose stops the effect on the lower dose neurotransmitter. I took the ceiling-scraping dose at 450mg for almost a decade specifically for its dopamine effect. Yes, XR holds you all day. Yes, generic is fine. Personally, I didn't experience anxiety at the norepinephrine level on the way up, not the way I did my first try on Wellbutrin. Just be alert for it, and inform your pdoc if it becomes an issue.

You may feel a bit of emotional numbing at higher doses, but you're not going to end up wandering around saying "Brainsss....."  For a lot of people the emotional numbing is the point.

Since your already on the Merry-Effexor-Go-Round, realize that going up is easy - coming off it is a bitch in the roller derby, and the more you're taking, the longer and more drawn-out the process is going to be. That's not a reason not to take it; when it works, it can be just what a person needs because it's so flexible. Effexor was the only thing that laid a glove on my depression until it finally pooped out on me after years. Just go into it with your eyes open.

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i hope this animation works

 

effexor titrates like this, where "s" is serotonin and "d" i used wrong wrong letter for neuropinefrin

 

duloxetine is opposite, Nr heavy at low doses becoming more serotonin heavy

 

to my knowledge

Edit see mia post 

Edited by DogMan
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Please could you remove the animation or change it to some sort of static diagram with an explanation.  Some of us are highly sensitive to flashing things on screens.  It is absolutely massive within the thread and also shows up with flashes in the activity feed, and I can't hide it unless I put you on ignore, which I do not want to do.   Thanks.

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17 minutes ago, MiaB said:

Please could you remove the animation or change it to some sort of static diagram with an explanation.  Some of us are highly sensitive to flashing things on screens.  It is absolutely massive within the thread and also shows up with flashes in the activity feed, and I can't hide it unless I put you on ignore, which I do not want to do.   Thanks.

Will be easier from laptop at home.

 

I'll be out a few hours. But feel free to superpower it away before then 

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10 hours ago, Blahblah said:

I've taken Venlafaxine in the past, but can folks here describe how different doses affected you? (i.e. different side effects at each dose?)  Would you recommend ONLY brand (or generic OK too?). I need to increase, but I'm afraid of the "numb zombie effect" happening at higher doses.....

Currently at 75mg, and feeling only typical Serotonergic effects (calm, drowsiness, lethargy, spaciness, dry mouth, blurry vision)

From what I read at 150mg, it primarily affects Norepinephrine (giving to a more energizing/possibly anxious feeling?) And at 225mg, it starts working on increasing Dopamine (I don't know how much in comparison to serotonin & NE ?)

Also, I want to switch to XR due to the longer half-life (and smoother withdrawal). Is the XR all-day coverage? (The instant can give brain zaps sometimes after wearing off)

I think @Cerberus gave some great answers and I’d agree with that post above …. I’m not sure that the 150 would “primarily” act on norepinephrine because as far as SNRIs go, Effexor is very skewed towards serotonin reuptake affinity (30:1 according to some sources, with pristiq and cymbalta being closer to 10:1, fetzima is the only SNRI for depression in the us that is actually more potent in norepinephrine reuptake than serotonin for those who find such things interesting) so I would state it more that nor kicks in at 150 at which point you will start to get significant reuptake of both

Edited by Iceberg
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  • 2 weeks later...
On 9/13/2022 at 11:41 AM, Blahblah said:

I've taken Venlafaxine in the past, but can folks here describe how different doses affected you? (i.e. different side effects at each dose?)  Would you recommend ONLY brand (or generic OK too?). I need to increase, but I'm afraid of the "numb zombie effect" happening at higher doses.....

Currently at 75mg, and feeling only typical Serotonergic effects (calm, drowsiness, lethargy, spaciness, dry mouth, blurry vision)

From what I read at 150mg, it primarily affects Norepinephrine (giving to a more energizing/possibly anxious feeling?) And at 225mg, it starts working on increasing Dopamine (I don't know how much in comparison to serotonin & NE ?)

Also, I want to switch to XR due to the longer half-life (and smoother withdrawal). Is the XR all-day coverage? (The instant can give brain zaps sometimes after wearing off)

I haven't been on Effexor in at least a few years, I think, so my memory is a little fuzzy about specifics, but I believe it starts to become slightly noradrenergic at either 150mg or maybe even 225mg and then dopaminergic at 300+mg. The highest I ever went to was 300mg, didn't notice much, if at all, difference, good or bad, and went back down to 225mg and stayed there for the majority of my time on it. 

At pretty much all doses 150mg and above, it was decent for my depression, but only took the edge off my social anxiety (and ultimately why I cross-tapered to Duloxetine). And the only side effect I noticed was moderate dry mouth for a few days after every dosage increase. That's it. 

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On 9/13/2022 at 3:52 PM, DogMan said:

i hope this animation works

 

effexor titrates like this, where "s" is serotonin and "d" i used wrong wrong letter for neuropinefrin

 

duloxetine is opposite, Nr heavy at low doses becoming more serotonin heavy

 

to my knowledge

Edit see mia post 

Venlafaxine, desvenlafaxine, and duloxetine are all serotonin heavy. Their effect on norepinephrine increases in the order they are listed. Venlafaxine has the least effect followed by desvenlafaxine, and then duloxetine.

A certain amount of transporter occupancy is required in order to elicit a significant downstream effect. With venlafaxine, the occupancy of the norepinephrine transporter does not become significant enough to elicit noradrenergic effect until ~150mg. You might get some effect at 75mg, but most of the effect is serotonergic.

By contrast, duloxetine has greater affinity for the norepinephrine transporter, although still less than for the serotonin transporter. However, the increase in norepinephrine transporter occupancy compared to venlafaxine is significant enough that effective transporter occupancy can be achieved at all doses. So while noradrenergic effect from duloxetine at 20-30mg may not be significant, it is still more significant than for 75mg venlafaxine. @Iceberg has the ratios below.

Levomilnacipran is basically the opposite of venlafaxine. Mostly noradrenergic at lower doses with escalating serotonergic effect as the dose increases.

On 9/13/2022 at 9:47 PM, Iceberg said:

I think @Cerberus gave some great answers and I’d agree with that post above …. I’m not sure that the 150 would “primarily” act on norepinephrine because as far as SNRIs go, Effexor is very skewed towards serotonin reuptake affinity (30:1 according to some sources, with pristiq and cymbalta being closer to 10:1, fetzima is the only SNRI for depression in the us that is actually more potent in norepinephrine reuptake than serotonin for those who find such things interesting) so I would state it more that nor kicks in at 150 at which point you will start to get significant reuptake of both

 

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On 9/13/2022 at 9:16 PM, Cerberus said:

Yes, the dosage increases do seem to target specific neurotransmitter areas, though I'm not sure if increasing the dose stops the effect on the lower dose neurotransmitter. I took the ceiling-scraping dose at 450mg for almost a decade specifically for its dopamine effect. Yes, XR holds you all day. Yes, generic is fine. Personally, I didn't experience anxiety at the norepinephrine level on the way up, not the way I did my first try on Wellbutrin. Just be alert for it, and inform your pdoc if it becomes an issue.

You may feel a bit of emotional numbing at higher doses, but you're not going to end up wandering around saying "Brainsss....."  For a lot of people the emotional numbing is the point.

Since your already on the Merry-Effexor-Go-Round, realize that going up is easy - coming off it is a bitch in the roller derby, and the more you're taking, the longer and more drawn-out the process is going to be. That's not a reason not to take it; when it works, it can be just what a person needs because it's so flexible. Effexor was the only thing that laid a glove on my depression until it finally pooped out on me after years. Just go into it with your eyes open.

Thank you. You were at a high dose forever. How long did it take to go off?  Did you have brain zaps & freak-outs for like a year? Now that you've been off for sometime, do you feel better/ worse? In what ways?

I'm disheartened to hear that Effexor is that Serotonin-heavy. I don't like the complete numbing apathy effect (I'm prone to dissociate). If I wanted just Serotonin, I'd go back on Prozac (soooooooo much easier / low maintenance!)  Admittedly, I'm aware Effexor has one of the worst withdrawal profiles. I'm terrified, if I keep going up it will be pure torment to go off....then months of scrambling to stabilize.

I'm at 112mg (2 weeks now). Feeling no difference at this dose. Lethargy, no energy, no interest, spaced out, no crying spells/ lability but still very depressed. It is really a fight for me to go back on this & stick it out. My gut feeling is, there is no med that will help me feel better, motivated, functioning. Antidepressants over time, eventually just make me feel apathetic/ numb and stimulants poop-out (or give the artificially wired then drained feeling) & that's not what I want anymore.

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6 hours ago, Blahblah said:

Thank you. You were at a high dose forever. How long did it take to go off?  Did you have brain zaps & freak-outs for like a year? Now that you've been off for sometime, do you feel better/ worse? In what ways?

From the time I started tapering off to the point at which I completely had it behind me was about three months, but the worst of the withdrawal was over with in 3-4 weeks. Brain zaps, definitely; I’m not sure I had what I would describe as ‘freak-outs’, but there were moments of ungoverned mood change that I was unaccustomed to. I also have a low tolerance for nausea, and there was a bit of that in the early days.

The key to getting through it was gra-a-a-a-adual titration down, to the point of opening the capsules at the end and taking smaller and smaller numbers of the little pill-lets inside, along with another antidepressant (in my case Wellbutrin) to smooth the ride.

Do I feel better or worse? I feel different. I don’t have as much cushion against depression that Effexor gave me, but I’m not as emotionally flat as I was on it either (for an Autistic person this isn’t necessarily an improvement). I have regained some of my creativity, but endure more of the mental pain. As with just about everything else in my life, there’s no silver lining without a cloud.

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In my most recent use of Effexor I was taking 75 mg of generic er. It really started giving me crazy strong side effects which doctors attributed to other health issues instead of the drug. This summer I tapered off but not before trying Prozac and Pristiq. Currently I am about 28 days free of Effexor. And I think @Cerberus explain things very well. It's a different feeling. Over the past two weeks though I've had some pretty bad depression starting again. I'm not sure I would go on another antidepressant though because most of them cause sleep issues and that is my biggest problem insomnia

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