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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by NKP on August 8, 2021, at 15:52:17
I've read that venlafaxine, at doses lower than 225 mg/day, works essentially like an SSRI. A meaningful dopaminergic effect only kicks in at very high doses. That being the case, is there any point to using venlafaxine, rather than an SSRI, at doses lower than 225 mg/day?
Here's a case report of a patient who became psychotic when using venlafaxine at a dose of 150 mg/day.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802382/
The probable cause for this psychosis was an increase in dopamine. Does this not contradict the claim that venlafaxine is basically an SSRI at these doses?
Context
++++++Previously I was taking sertraline 50 mg/day and flupenthixol 0.5 mg/day. My mood was fine but my functioning was very poor (extreme lack of motivation). This medication was being prescribed through my family doctor.
I finally went to see a psychiatrist a few weeks back after my wife threatened to divorce me if I didn't see a psychiatrist *and* abide by his treatment (I have a tendency to consult with Dr Google). He took me off the sertraline and flupenthixol, and replaced it with 75 mg/day venlafaxine.
I notice no real difference except perhaps I feel a bit more energetic. My wife however claims that my mood has substantially improved.
I don't really know what to do because my functioning is very poor.
The psychiatrist said that future options would be to increase the dose of venlafaxine, and if that didn't work, to consider augmenting with quetiapine or lamotrigine.
Do you think that this might improve my functioning?
Posted by linkadge on August 9, 2021, at 6:54:25
In reply to Low dose venlafaxine basically an SSRI?, posted by NKP on August 8, 2021, at 15:52:17
On paper, effexor can become dopaminergic in VERY high does. However, in vivo, there is no evidence that effexor actually occupies the dopamine transporter in the human brain (even at the top of the dose range). The psychotic reaction you mentioned was only hypothesized to be related to dopamine, there was no objective evidence of this.
There have been studies showing that effexor can affect norepinephrine even in lower doses (75mg) and this effect is dose dependent. Yes, it primarily affects serotonin, but there will still be some noradrenergic action. This becomes more pronounced in higher doses.
So, yes increasing the dose could very well lead to additional therapeutic effect.
Linkadge
Posted by NKP on August 9, 2021, at 10:18:48
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by linkadge on August 9, 2021, at 6:54:25
> On paper, effexor can become dopaminergic in VERY high does. However, in vivo, there is no evidence that effexor actually occupies the dopamine transporter in the human brain (even at the top of the dose range). The psychotic reaction you mentioned was only hypothesized to be related to dopamine, there was no objective evidence of this.
>
> There have been studies showing that effexor can affect norepinephrine even in lower doses (75mg) and this effect is dose dependent. Yes, it primarily affects serotonin, but there will still be some noradrenergic action. This becomes more pronounced in higher doses.
>
> So, yes increasing the dose could very well lead to additional therapeutic effect.
>
> LinkadgeThank you for this information.
Everywhere I look, I see people badmouthing venlafaxine, saying it's basically an SSRI with the side-effects of an SNRI, hence why I was wondering. But I will trust my doctor and stick to the treatment.
Posted by linkadge on August 9, 2021, at 15:51:48
In reply to Re: Low dose venlafaxine basically an SSRI? » linkadge, posted by NKP on August 9, 2021, at 10:18:48
It doesn't really make sense to have an SSRI with the side effects of an SNRI. If it has side effects consistent with an SNRI then it must have some effects on norepinephrine.
On paper, venlafaxine's occupancy of the norepinephrine transporter is lowish. However, PET studies have shown much higher occupancy than you'd expect.
https://pubmed.ncbi.nlm.nih.gov/23090625/
https://pubmed.ncbi.nlm.nih.gov/18418363/
https://pubmed.ncbi.nlm.nih.gov/30649319/
Linkadge
Posted by NKP on August 10, 2021, at 5:33:56
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by linkadge on August 9, 2021, at 15:51:48
> It doesn't really make sense to have an SSRI with the side effects of an SNRI. If it has side effects consistent with an SNRI then it must have some effects on norepinephrine.
>
> On paper, venlafaxine's occupancy of the norepinephrine transporter is lowish. However, PET studies have shown much higher occupancy than you'd expect.
>
> https://pubmed.ncbi.nlm.nih.gov/23090625/
>
> https://pubmed.ncbi.nlm.nih.gov/18418363/
>
> https://pubmed.ncbi.nlm.nih.gov/30649319/
>
> LinkadgeThank you for this information. That is very interesting.
Posted by undopaminergic on August 10, 2021, at 11:45:47
In reply to Low dose venlafaxine basically an SSRI?, posted by NKP on August 8, 2021, at 15:52:17
>
> The psychiatrist said that future options would be to increase the dose of venlafaxine, and if that didn't work, to consider augmenting with quetiapine or lamotrigine.
>I would add the flupenthixol back much rather than quetiapine. Other options amongst antipsychotics are amisulpride, sulpiride, lurasidone, cariprazine, or even ziprasidone. All of them are less sedating than quetiapine, and can even be activating, especially with low doses. However, I think the lamotrigine is worth trying, and increasing the venlafaxine is not a bad idea, at least if you tolerate it well.
As for motivation, stimulants come immediately to mind, including methylphenidate and dextroamphetamine.
-undopaminergic
Posted by SLS on August 11, 2021, at 11:53:03
In reply to Low dose venlafaxine basically an SSRI?, posted by NKP on August 8, 2021, at 15:52:17
Hi.
> I've read that venlafaxine, at doses lower than 225 mg/day, works essentially like an SSRI.
There is no one better to answer that question than Linkadge. He would do a much better job at describing the most up-to-date facts and theories. I will let him address questions of pharmacology.If you have had multiple treatment failures, don't worry so much about the pharmacology of venlafaxine and consider it a brand new chemical that you are exposing your brain to. Even at low dosages, it might act in the body in ways yet to be discovered. Personally, I responded better to venlafaxine than any SSRI. I had to go to 300 mg/day to gain maximal antidepressant efficacy. For me, side effects waned until they disappeared entirely. As an example of an effect produced by venlafaxine for me and not for any other drug, after my very first dose of 37.5 mg, I became intensely nauseous and dry-heaved for a few minutes. It never reappeared. Different is different. The only drawback to venlafaxine is that it is difficult to discontinue it due to withdrawal effects. Of course, if it works, this wouldn't be an issue if you intended to stay on it in perpetuity.
Let me amplify my point: Is there anyone you know who responded to one SSRI after failing to respond to another?
Good luck.
- Scott
Posted by NKP on August 13, 2021, at 5:15:02
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by undopaminergic on August 10, 2021, at 11:45:47
> >
> > The psychiatrist said that future options would be to increase the dose of venlafaxine, and if that didn't work, to consider augmenting with quetiapine or lamotrigine.
> >
>
> I would add the flupenthixol back much rather than quetiapine. Other options amongst antipsychotics are amisulpride, sulpiride, lurasidone, cariprazine, or even ziprasidone. All of them are less sedating than quetiapine, and can even be activating, especially with low doses. However, I think the lamotrigine is worth trying, and increasing the venlafaxine is not a bad idea, at least if you tolerate it well.
>
> As for motivation, stimulants come immediately to mind, including methylphenidate and dextroamphetamine.
>
> -undopaminergic
>Then I doubt that I'll go on quetiapine because I'm already sleepy much of the time.
Posted by NKP on August 13, 2021, at 5:17:49
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by SLS on August 11, 2021, at 11:53:03
> Hi.
>
> > I've read that venlafaxine, at doses lower than 225 mg/day, works essentially like an SSRI.
>
>
> There is no one better to answer that question than Linkadge. He would do a much better job at describing the most up-to-date facts and theories. I will let him address questions of pharmacology.
>
> If you have had multiple treatment failures, don't worry so much about the pharmacology of venlafaxine and consider it a brand new chemical that you are exposing your brain to. Even at low dosages, it might act in the body in ways yet to be discovered. Personally, I responded better to venlafaxine than any SSRI. I had to go to 300 mg/day to gain maximal antidepressant efficacy. For me, side effects waned until they disappeared entirely. As an example of an effect produced by venlafaxine for me and not for any other drug, after my very first dose of 37.5 mg, I became intensely nauseous and dry-heaved for a few minutes. It never reappeared. Different is different. The only drawback to venlafaxine is that it is difficult to discontinue it due to withdrawal effects. Of course, if it works, this wouldn't be an issue if you intended to stay on it in perpetuity.
>
> Let me amplify my point: Is there anyone you know who responded to one SSRI after failing to respond to another?
>
> Good luck.
>
>
> - ScottSo far I seem to be doing OK on the venlafaxine. I've only been on it for a few weeks but it seems like as time goes on, I'm developing new effects and side-effects. So I'll be patient and give it a fair chance.
Posted by NKP on August 13, 2021, at 7:43:58
In reply to Re: Low dose venlafaxine basically an SSRI? » SLS, posted by NKP on August 13, 2021, at 5:17:49
Historically I've almost never gotten headaches.
When I took atomoxetine last year, I had regular headaches, particularly when waking up in the mornings. I reckon that this was from the noradrenergic effect of the atomoxetine, since that's mostly what atomoxetine does.
Now on venlafaxine, I'm starting to get headaches again. This suggests to me that I *am* experiencing a noradrenergic effect from venlafaxine, even though many sources claim that this only starts happening at around 225 mg/day.
Of course, the articles that Linkadge posted, show that there may be significant noradrenergic effects at lower doses too.
Posted by undopaminergic on August 13, 2021, at 9:15:26
In reply to Re: Low dose venlafaxine basically an SSRI? » undopaminergic, posted by NKP on August 13, 2021, at 5:15:02
> > >
> > > The psychiatrist said that future options would be to increase the dose of venlafaxine, and if that didn't work, to consider augmenting with quetiapine or lamotrigine.
> > >
> >
> > I would add the flupenthixol back much rather than quetiapine. Other options amongst antipsychotics are amisulpride, sulpiride, lurasidone, cariprazine, or even ziprasidone. All of them are less sedating than quetiapine, and can even be activating, especially with low doses. However, I think the lamotrigine is worth trying, and increasing the venlafaxine is not a bad idea, at least if you tolerate it well.
> >
> > As for motivation, stimulants come immediately to mind, including methylphenidate and dextroamphetamine.
> >
> > -undopaminergic
> >
>
> Then I doubt that I'll go on quetiapine because I'm already sleepy much of the time.
>As a piece of trivia, I am prescribed quetiapine at night PRN (as needed) for sleep!
-undopaminergic
Posted by SLS on August 16, 2021, at 11:01:17
In reply to Re: Low dose venlafaxine basically an SSRI? » SLS, posted by NKP on August 13, 2021, at 5:17:49
> > Hi.
> >
> > > I've read that venlafaxine, at doses lower than 225 mg/day, works essentially like an SSRI.
> >
> >
> > There is no one better to answer that question than Linkadge. He would do a much better job at describing the most up-to-date facts and theories. I will let him address questions of pharmacology.
> >
> > If you have had multiple treatment failures, don't worry so much about the pharmacology of venlafaxine and consider it a brand new chemical that you are exposing your brain to. Even at low dosages, it might act in the body in ways yet to be discovered. Personally, I responded better to venlafaxine than any SSRI. I had to go to 300 mg/day to gain maximal antidepressant efficacy. For me, side effects waned until they disappeared entirely. As an example of an effect produced by venlafaxine for me and not for any other drug, after my very first dose of 37.5 mg, I became intensely nauseous and dry-heaved for a few minutes. It never reappeared. Different is different. The only drawback to venlafaxine is that it is difficult to discontinue it due to withdrawal effects. Of course, if it works, this wouldn't be an issue if you intended to stay on it in perpetuity.
> >
> > Let me amplify my point: Is there anyone you know who responded to one SSRI after failing to respond to another?
> >
> > Good luck.
> >
> >
> > - Scott
>
> So far I seem to be doing OK on the venlafaxine. I've only been on it for a few weeks but it seems like as time goes on, I'm developing new effects and side-effects. So I'll be patient and give it a fair chance.
Please do.What dosage are you at?
How quickly did you titrate?
What side effects did you experience at the beginning?
What side effects emerged more recently? Did they occur immediately after a dosage increase?
It is early in treatment, but some people feel a subtle hint of improvement at the beginning of the third week. If you feel a little better, go for it. Take venlafaxine for at least 8 more weeks and try working up to 225-300 mg/day AS TOLERATED for perhaps 8 more weeks. Gradual is better than rapid. Rapid dosage increases can trigger previously absent side effects or make existing side effects worse. If tolerability becomes a problem, you might consider reducing the dosage for awhile and allow the side effects to disappear, and then increase it more gruadually.
If you are improved, but get stuck and plateau, I would add Wellbutrin at 300 mg/day.
Let us know the answer to those question. They might be helpful to you.
Good luck!
- Scott
Posted by NKP on August 25, 2021, at 4:50:34
In reply to Re: Low dose venlafaxine basically an SSRI? » NKP, posted by SLS on August 16, 2021, at 11:01:17
A week ago my doctor increased my dose of venlafaxine to 150 mg/day.
I feel like I'm getting worse, not better. Not only am I still not functioning well, I'm also beginning to feel depressed.
If it carries on, I might phone him and ask that I go back to sertraline and flupenthixol. I wasn't functioning well on sertraline and flupenthixol, but at least I didn't feel depressed.
The idea of phoning him makes me feel like I'm a burden however, and I feel guilty about the money that it will cost. That's probably another cognitive distortion.
Posted by linkadge on August 25, 2021, at 7:36:39
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by NKP on August 25, 2021, at 4:50:34
Yeah, if you're feeling worse with a dose change, you might wait a few days. However, after this (assuming no benefit) I wouldn't take more.
Linkadge
Posted by linkadge on August 25, 2021, at 7:37:46
In reply to Re: Low dose venlafaxine basically an SSRI?, posted by NKP on August 25, 2021, at 4:50:34
Sorry, that last message wasn't worded well.
I meant .. give it a few days, but after that I would go back to the dose where you felt better.
Not every med works for every individual.
Linkadge
This is the end of the thread.
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