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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by cornfedboy on May 28, 2007, at 21:01:51
I just can't seem to get a straight answer on this one, or find hard data on the Internet.
Fact1: At low doses (37.5 to 150) venlafaxine works basically like an SSRI.
Fact2: At higher doses (150? to 300?) it's effect on serotonin plateaus and the norepinephrine activity kicks in.
But what about dopamine? Everywhere I look I'm told that Effexor "weakly" affects dopamine reuptake. How weak? And at what dose? Some say that the dopaminergic effects kick in around 300; others say 375; still others say 600.
Is there any hard data on this?
BTW, I'm on 300 mg of Effexor XR. I feel fine. But low motivation has always been an issue for me, hence the interest in venlafaxine's action on dopamine.
Thanks!
Cornfedboy
Posted by Phillipa on May 28, 2007, at 21:07:35
In reply to Effexor and dopamine, posted by cornfedboy on May 28, 2007, at 21:01:51
Gee I hadn't heard that effexor affected dopamine thought just serotonin and norepenephrine. I may learn a lot on this thread. Love Phillipa ps isn't that why people add wellbutrin for dopamine?
Posted by cornfedboy on May 28, 2007, at 21:25:26
In reply to Re: Effexor and dopamine » cornfedboy, posted by Phillipa on May 28, 2007, at 21:07:35
Yes, one common augmentation strategy is adding bupropion. Some anecdotal reports suggest that adding Wellbutrin to an SSRI/SNRI regime can alleviate some sexual dysfunction side effects.
Well, Wellbutrin just doesn't do well with me. I feel agitated, and lose weight. Also, it did nothing for my delayed orgasm problem.
I should add that I take 1.5 mg of Klonopin and 50 mg of Seroquel at night for insomnia.
I'm curious: has anyone increased their Effexor dose, on their Pdoc's advice perhaps, specifically to get some dopamine "action"? Such as going from 300 to 375 or higher?
Again, factual and anecdotal reports both appreciated.
Cornfedboy
Posted by Phillipa on May 28, 2007, at 21:29:24
In reply to Re: Effexor and dopamine, posted by cornfedboy on May 28, 2007, at 21:25:26
I don't know I googled it and it only mentioned serotonin and norepenephrine in the med. Love Phillipa
Posted by linkadge on May 29, 2007, at 6:39:22
In reply to Re: Effexor and dopamine » cornfedboy, posted by Phillipa on May 28, 2007, at 21:29:24
Effexor will affect the monoamines in a fixed ratio that does not change with increaing the dose.
What people mean when they say the norepinephrine effects "kick in" at higher doses, is that for some people higher doses are needed before a noradrenergic effect is felt.
The drug will inhibit the norepinephrine reuptake pump dose dependandtly.
Depending on your sensitivty to it, some can feel the noradrenergic effects at very low doses.
The serotonergic effects do not stop at a certain dose either. The more drug, the more reuptake inhibition.
I don't know what dose one would need for a pronounced dopaminergic effect. Probably a LOT, as it is a very weak inhibitor of dopamine reuptake.Linkadge
Posted by Klavot on May 29, 2007, at 7:25:08
In reply to Re: Effexor and dopamine, posted by linkadge on May 29, 2007, at 6:39:22
If Effexor could inhibit dopamine reuptake significantly, then this would be a strong marketing point and Wyeth would promote it. So if the manufacturer does not claim any dopaminergic effect, then there probably is none.
Klavot
Posted by cornfedboy on May 29, 2007, at 9:33:12
In reply to Re: Effexor and dopamine, posted by linkadge on May 29, 2007, at 6:39:22
> Effexor will affect the monoamines in a fixed ratio that does not change with increaing the dose.
>
> What people mean when they say the norepinephrine effects "kick in" at higher doses, is that for some people higher doses are needed before a noradrenergic effect is felt.
>
> The drug will inhibit the norepinephrine reuptake pump dose dependandtly.
>
> Depending on your sensitivty to it, some can feel the noradrenergic effects at very low doses.
>
> The serotonergic effects do not stop at a certain dose either. The more drug, the more reuptake inhibition.
>
>
> I don't know what dose one would need for a pronounced dopaminergic effect. Probably a LOT, as it is a very weak inhibitor of dopamine reuptake.
>
> Linkadge
Linkadge, I'm by no means an expert o any of this and you may be right But: logically speaking, wouldn't the serotonergic effects have to level off at at some point. I mean, if 5-HT reuptake inhibition is (say) 95% at a dose of 150, it can hardly be 190% at a dose of 300. At most it can be 99%+ or something like that. Similarly with the SSRIs: if with a particular person, maximal reuptake inhibition is achieved at a dose of 40 mg of Prozac, adding another 40 mg isn't going to do much. The pharmokinetics aren't linear. Am I right about this?And do we have specifics on the very weak dopamine reuptake, both in vitro and in vivo?
Cornfedboy
Posted by cornfedboy on May 29, 2007, at 9:45:57
In reply to Re: Effexor and dopamine, posted by Klavot on May 29, 2007, at 7:25:08
https://www.dr-bob.org/babble/20040417/msgs/338640.html
http://www.dr-bob.org/babble/20020914/msgs/120373.html
http://www.dr-bob.org/babble/20020402/msgs/101450.html
Once again with this topic, lotsa questions, not that many clearcut or consensual answers based on research.
Cornfedboy
Posted by Flame on May 29, 2007, at 12:26:34
In reply to Effexor and dopamine, posted by cornfedboy on May 28, 2007, at 21:01:51
Hi There,
I'm not sure I've "followed" correctly all that has been relayed on this thread.
But .. just thought I'd tell you that my husband has been on 375mgs. of Effexor XR for 3 years now.
Much to my dismay, I have discovered that my husband has "decided" that he can no longer work. He was previously self-employed .. for approximately 30 yrs. For the past year or so, he constantly claims that there is no work out there.
A light-bulb moment "happened" for me, not too long ago, and I realized he has just decided that he is finished with "working".
Unfortunately he DOES have the "ambition" to do all that he wants to do with hobbies, etc .. just not to work. He claims that he is not able to remember things like he used to, nor does he have the patience.
Nightly .. he ALSO takes ambien and mirapex. In the morning he takes provigil. I don't know if any of these could be adding to his "lack of motivation for work" issues ..?
Anyway .. just thought I'd throw that out there. Needless to say it has created many worries for me, since we can't afford him being in this "frame of mind".
Molly
Posted by Klavot on May 29, 2007, at 12:26:44
In reply to Re: Effexor and dopamine, posted by cornfedboy on May 29, 2007, at 9:33:12
I seem to recall that Zoloft inhibits serotonin reuptake by 80 % at 50 mg / day and 100 % at 200 mg / day. Check out Sheldon Preskorn's website for many interesting articles on this:
As I recall, he made the point that it is not worthwhile quadrupling the dose of Zoloft and thereby "quadrupling" side-effects for a mere 20 % extra benefit.
There is an article on Effexor answering some of your questions at
http://www.preskorn.com/columns/9911.html
Bear in mind that the interpretation of "binding affinities" etc. is tricky and subject to many paramaters. If I understand correctly, greater binding affinity does not necessarily mean more potency.
For what it's worth, I personally think that dopamine is overrated. Read the Wikipedia article at
http://en.wikipedia.org/wiki/Dopamine
They make the point that dopamine may actually regulate desire rather than motivation. It so happens that desire is a strong motivator.
Klavot
Posted by linkadge on May 30, 2007, at 10:46:20
In reply to Re: Effexor and dopamine, posted by cornfedboy on May 29, 2007, at 9:33:12
I don't think you'd get near 95% inhibition of serotonin utpake, but I see your logic.
Yes, I suppose at the higher doses you would get a more pronounced effect on the noradrenergic pump than you would on the serotonin pump.
I guess I am really disagreeing with the notion that it takes a certain dose before the noradrenergic effects kick in.
My argument is that effexor will inhibit norepinephrine reuptake at all doses, but perhaps it doesn't become pronounced untill higher doses.
Linkadge
Posted by linkadge on May 30, 2007, at 10:48:30
In reply to Re: Effexor and dopamine - cornfedboy, posted by Flame on May 29, 2007, at 12:26:34
Unfortunatly, sometimes these drugs can sometimes reduce fear too much, to the point where people develop a "who cares" type of attitude to anxieties or failures.
Linkadge
Posted by Flame on May 30, 2007, at 11:55:52
In reply to Re: Effexor and dopamine - cornfedboy » Flame, posted by linkadge on May 30, 2007, at 10:48:30
"Unfortunatly, sometimes these drugs can sometimes reduce fear too much, to the point where people develop a "who cares" type of attitude to anxieties or failures."
Link,
What you say makes sense to me .. I think?
After being on all of those (newer, at that time) meds for six months, my husband began drinking .. very heavily. That was three years ago and things have just gone down hill since then.
I tried not to make it my problem .. and thought that maybe something major would happen and he would hit "bottom" on his own.
After numerous conversations/arguments, with me "telling" husband that he must get back to work .. it finally "hit" me. I realized that he does not plan on ever going back to work on a regular basis.
What a terrible waste! Unfortunately .. I am at the end of my rope. His drinking is obviously HIS problem .. but NOW, when we are in the financial difficulty we are in .. that becomes MY problem.
I am in the process of writing a letter to husband's pdoc (his psychiatrist asked me to) to fill him in on all that is going on, 'cause my husband sure isn't telling his doc the truth at those three month med check appointments.
Whew!! Okay .. I've vented. Thanks for letting me "get it out"!!
I appreciate your response Link!
Molly
Posted by linkadge on May 30, 2007, at 15:00:09
In reply to Re: Effexor and dopamine, posted by Klavot on May 29, 2007, at 12:26:44
Another thing to consider is that this data was probably calculated in animals after one time dosings of these drugs.
I don't think it is taking into account the degree of transporter upregulation that will occur after long term dosing.
Ie, as an adaptive response to uptake inhibitors, the brain usually starts producing more transporter. For instance, with cocaine, a dose that initially inhibited DAT by 50% is unlikely to do so after repeated doses as the brain starts to produce more DAT.
Linkadge
Posted by Lonely on May 30, 2007, at 23:38:25
In reply to Re: Effexor and dopamine - cornfedboy, posted by Flame on May 29, 2007, at 12:26:34
To me it seems obvious that the meds are doing something to him. My hubby was on Effexor twice and in retrospect I (and I think even he) realize it made his manic and ensuing depression even worse. And getting off from it with an uneducated psychiatrist (ironically a volunteer at a local med school) was ... well ... I'm sure you can think of a word. At the time he missed a lot of work plus he was an alcoholic. I was the one who intervened and in a psychological sense got slapped down and belittled by the psychiatrist plus my hubby who portrayed me to the neuropsychologist (not board certified) as denying him meds. It was necessary and I'm glad I did it. No more antidepressants for him - he's on Lamictal alone now and better. I go w/him to all doctor visits.
> Hi There,
>
> I'm not sure I've "followed" correctly all that has been relayed on this thread.
>
> But .. just thought I'd tell you that my husband has been on 375mgs. of Effexor XR for 3 years now.
>
> Much to my dismay, I have discovered that my husband has "decided" that he can no longer work. He was previously self-employed .. for approximately 30 yrs. For the past year or so, he constantly claims that there is no work out there.
>
> A light-bulb moment "happened" for me, not too long ago, and I realized he has just decided that he is finished with "working".
>
> Unfortunately he DOES have the "ambition" to do all that he wants to do with hobbies, etc .. just not to work. He claims that he is not able to remember things like he used to, nor does he have the patience.
>
> Nightly .. he ALSO takes ambien and mirapex. In the morning he takes provigil. I don't know if any of these could be adding to his "lack of motivation for work" issues ..?
>
> Anyway .. just thought I'd throw that out there. Needless to say it has created many worries for me, since we can't afford him being in this "frame of mind".
>
> Molly
>
Posted by Lonely on May 30, 2007, at 23:42:15
In reply to Re: Effexor and dopamine » linkadge, posted by Flame on May 30, 2007, at 11:55:52
Oh-my-goodness, I just responded to an earlier poster in this thread before I read your post. What you wrote could have almost been me !!! I can't believe it - there's something to this.
If you'd like, I'll pm w/you and compare notes if you're comfortable with that.
> "Unfortunatly, sometimes these drugs can sometimes reduce fear too much, to the point where people develop a "who cares" type of attitude to anxieties or failures."
>
> Link,
>
> What you say makes sense to me .. I think?
>
> After being on all of those (newer, at that time) meds for six months, my husband began drinking .. very heavily. That was three years ago and things have just gone down hill since then.
>
> I tried not to make it my problem .. and thought that maybe something major would happen and he would hit "bottom" on his own.
>
> After numerous conversations/arguments, with me "telling" husband that he must get back to work .. it finally "hit" me. I realized that he does not plan on ever going back to work on a regular basis.
>
> What a terrible waste! Unfortunately .. I am at the end of my rope. His drinking is obviously HIS problem .. but NOW, when we are in the financial difficulty we are in .. that becomes MY problem.
>
> I am in the process of writing a letter to husband's pdoc (his psychiatrist asked me to) to fill him in on all that is going on, 'cause my husband sure isn't telling his doc the truth at those three month med check appointments.
>
> Whew!! Okay .. I've vented. Thanks for letting me "get it out"!!
>
> I appreciate your response Link!
>
> Molly
>
>
>
>
>
>
Posted by Flame on May 31, 2007, at 8:00:29
In reply to Re: Effexor and dopamine » Flame, posted by Lonely on May 30, 2007, at 23:42:15
Hi Lonely,
I am VERY interested in communicating with you more.
I sent you a "babble" mail. Please check that.
Thanks!
Posted by Flame on May 31, 2007, at 8:05:57
In reply to Re: Effexor and dopamine - cornfedboy » Flame, posted by Lonely on May 30, 2007, at 23:38:25
This is confounding for me. How bizarre that these pdoc's are not correlating the extreme changes .. going "down hill" to the new meds that they are put on??
I went to one of husbands appts., years back (at the beginning) and mentioned the fact that I thought that husband seemed to do very well AT FIRST on his new meds. I relayed to husband AND his doc just that and also mentioned that it started going downhill at the 6 month mark .. coincidentally .. that is when he started drinking heavily.
So very infuriating and frustrating!
Posted by linkadge on May 31, 2007, at 11:01:49
In reply to Re: Effexor and dopamine - cornfedboy » Lonely, posted by Flame on May 31, 2007, at 8:05:57
My mother was put on meds for bipolar. As the doses increased her ability to do anything decreased. She had to quit her job, and eventually did less and less. Now she just lies around all day, medicating every little problem.
Every time she pops a pill to solve a problem, a little piece of her will & ambition to be somebody dies.
Sometimes these meds "work" by creating emotional indifference to ones problems. You can't be anxious about something you don't care about.
For many people who take these drugs, this new state of indifference is more comfortable than where they were. It is not "recovery" by any strech of the imagination, it is just a more comfortable place, so they go along with it.
Linkadge
Posted by Flame on May 31, 2007, at 12:05:01
In reply to Re: Effexor and dopamine - cornfedboy, posted by linkadge on May 31, 2007, at 11:01:49
Link,
This makes TOTAL sense to me!
What I am wondering is how does my husband have all of the energy/motivation that he DOES have, to do so many OTHER things? .. IF, in fact, his meds ARE causing him to be indifferent, etc?
This is probably not 100% accurate, but it appears to me that he has the "mmmph" to do many things that would be considered "hobbies". (and of course the "mmmph" to get up to the bar, drink and socialize with his "bar friends"!) Husbands hobbies can be/are quite taxing on energy levels also. Just makes me wonder .. ?
"For many people who take these drugs, this new state of indifference is more comfortable than where they were. It is not "recovery" by any strech of the imagination, it is just a more comfortable place, so they go along with it."
So .. maybe in my husband's situation, the hobbies (and such) were not/are not a source of anxiety .. so he is able to STILL do all of these things without a problem .. ? (Maybe I'm understanding this wrong. I'm just trying to make sense of my husbands situation.)
Posted by linkadge on May 31, 2007, at 19:11:07
In reply to Re: Effexor and dopamine » linkadge, posted by Flame on May 31, 2007, at 12:05:01
>So .. maybe in my husband's situation, the >hobbies (and such) were not/are not a source of >anxiety .. so he is able to STILL do all of >these things without a problem .. ? (Maybe I'm >understanding this wrong. I'm just trying to >make sense of my husbands situation.)
Well, there are always things in life that we don't want to do but have to do.
It may have less to do with energy/motivation, and more to do with a healthy level of anxiety.
A helthy level of anxiety can prepare us help us adapt to our environment. The right amount of anxiety can help us to refocus us on what is important.
Sometimes psychotropic drugs can work by altering our preceptions of what is important. Its just like how mothers who do a lot of methamphetamines will often do anything do get the drug, even at the expense of friends family etc.
I am not saying effexor is methamphetamine, I am just saying that sometimes these drugs can really alter our sense of what is important in our lives.
For example, sometimes certain drugs made me indifferent to peoples emotions. Sometimes they made me care less about school performance. Sometimes I stopped bathing, or caring about the way I looked.
I would have been content to just be a bumb on the street so long as I had money for food.
Now I can't speak for everbody, obviously, but thats just how some of these meds affected me.
Linakdge
Posted by Phillipa on May 31, 2007, at 21:22:40
In reply to Re: Effexor and dopamine, posted by linkadge on May 31, 2007, at 19:11:07
Link I think I better stop or lower the luvox instead of increasing it as I can't cry anymore so no emotional outlet which is why I think people become suicidal on ad's . No other way to express emotions. I think I will go back down to 50mg from l00mg. Love Phillipa
Posted by Lonely on June 1, 2007, at 0:48:57
In reply to Re: Effexor and dopamine » Lonely, posted by Flame on May 31, 2007, at 8:00:29
Thank you, Flame. Yes, I received your babble mail and have responded this evening.
It seems like this aspect of psychotropic drugs isn't talked about all that much - the disinterest or "shutting down" - or even the meanness that I experienced w/my hubby.
Frankly, these types of side effects really scare me!
I'm so glad the topic has been brought up in this forum and thanks to the many posters in this thread who have explained about the effect that psychotropic drugs can have in changing personalities and withdrawal from normal activities. Definitely, it should be brought out in the open more.
Thanks to all of you.
> Hi Lonely,
>
> I am VERY interested in communicating with you more.
>
> I sent you a "babble" mail. Please check that.
>
> Thanks!
Posted by Flame on June 1, 2007, at 7:41:36
In reply to Re: Effexor and dopamine » Flame, posted by Lonely on June 1, 2007, at 0:48:57
"It seems like this aspect of psychotropic drugs isn't talked about all that much - the disinterest or "shutting down" - or even the meanness that I experienced w/my hubby. "
I, too .. am very glad that I found this topic and chose to "vent" here. This thread has helped me (hugely!) in putting my finger on what is more than likely going on with my husband because of the meds he has been on for the past three years.
This thread, giving me another huge "light-bulb" moment will help me in communicating with husband's psychiatrist.
It's kind of scarey though, 'cause husband used to go into "rages" very easily. Those have been (more or less) minimized since he has been on the Effexor .. but the downside is the obvious .. NOT working and spending a lot of money on his drinking. (There IS more .. but that is the "jist" of it ..)
Lonely .. I DID get your email and am in the process of responding.
Best To All ..
Flame
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