Shown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Anna Laura on June 19, 2002, at 7:42:17
I started Wellbutrin about four weeks ago (also taking Effexor, 150 mg.)
I began taking 150 mg. the first week, then i went on 300 mg. the second week.
I'm on 450 mg. since yesterday.
I didn't experience anxiety or inner tension at all, just felt a little spacey the first couple of days.
After a few days i began to feel something, namely my 12 years anhedonia began to vanish and i was experiencing a calm, mild pleasurable feeling; it felt like my childhood depression sort of, and that was a positive sign to me since i had recovered from that type of depression; unfortunately that positive feeling didn't last. Just after the vanishing of the positive effect, i began to experience a transient extrapyramidal symptom, namely an involuntarly twiching of the tongue. Could this symptom be related to dopamine depletion?
I'm aware Bupropion is generally thought to be a dopaminergic drug, nonetheless, i read somewhere that 's a partial agonist, meaning has both agonistic and antagonistic properties, thus blocking and enhancing dopamine at the same time; moreover, it was especially designed not to induce any "high" or pleasurable feeling. A few studies outlined the weak dopaminergic effect of the drug.
Can some of you guys relate to those findings at all? Or may be my dopamine receptors are to blame, possibly having been depleted by a long lasting anhedonia?
Posted by JohnX2 on June 21, 2002, at 0:36:04
In reply to Wellbutrin extrapyramidal effects?, posted by Anna Laura on June 19, 2002, at 7:42:17
>
> I started Wellbutrin about four weeks ago (also taking Effexor, 150 mg.)
> I began taking 150 mg. the first week, then i went on 300 mg. the second week.
> I'm on 450 mg. since yesterday.
> I didn't experience anxiety or inner tension at all, just felt a little spacey the first couple of days.
> After a few days i began to feel something, namely my 12 years anhedonia began to vanish and i was experiencing a calm, mild pleasurable feeling; it felt like my childhood depression sort of, and that was a positive sign to me since i had recovered from that type of depression; unfortunately that positive feeling didn't last. Just after the vanishing of the positive effect, i began to experience a transient extrapyramidal symptom, namely an involuntarly twiching of the tongue. Could this symptom be related to dopamine depletion?
> I'm aware Bupropion is generally thought to be a dopaminergic drug, nonetheless, i read somewhere that 's a partial agonist, meaning has both agonistic and antagonistic properties, thus blocking and enhancing dopamine at the same time; moreover, it was especially designed not to induce any "high" or pleasurable feeling. A few studies outlined the weak dopaminergic effect of the drug.
> Can some of you guys relate to those findings at all? Or may be my dopamine receptors are to blame, possibly having been depleted by a long lasting anhedonia?Wellbutrin has a very narrow therapeutic range.
It is actually a pro-drug (the parent compound
bupropion is not involved much in the response, it
is the metabolites, pricipally hydroxybupropion that
are believed to do the work). The metabolites have
a longer 1/2 life (like 20+ hrs for hydroxybupropion),
and so they take a while to build up in your body and
reach a steady state. Just a guess, but its possible you
"passed through" the therapeutic window, maybe lowering the
dosage would help.Some people believe that wellbutrin at really strong doses
(metabolites above the thereapeutic range), actually indirectly
increases the firing of serotonin neurons via an interaction
between the increased Noradrenaline and serotonin.This is another off the wall hypothesis....
One of the metabolites hydroxybupropion is believe to
primarily be metabolized through the liver enzyme CYP 2D6.
At very high levels I believe it may swamp that enzyme.
I read a paper once suggesting that medicines that inhibit
CYP 2D6 may cause EPS. I don't remember the working hypothesis
though and it wasn't really substantiated (more of a guess).
I should try to dig that one up.Just some wild guesses.
Good Luck,
John
Posted by JohnX2 on June 21, 2002, at 0:58:12
In reply to Re: Wellbutrin extrapyramidal effects? » Anna Laura, posted by JohnX2 on June 21, 2002, at 0:36:04
> >
> > I started Wellbutrin about four weeks ago (also taking Effexor, 150 mg.)
> > I began taking 150 mg. the first week, then i went on 300 mg. the second week.
> > I'm on 450 mg. since yesterday.
> > I didn't experience anxiety or inner tension at all, just felt a little spacey the first couple of days.
> > After a few days i began to feel something, namely my 12 years anhedonia began to vanish and i was experiencing a calm, mild pleasurable feeling; it felt like my childhood depression sort of, and that was a positive sign to me since i had recovered from that type of depression; unfortunately that positive feeling didn't last. Just after the vanishing of the positive effect, i began to experience a transient extrapyramidal symptom, namely an involuntarly twiching of the tongue. Could this symptom be related to dopamine depletion?
> > I'm aware Bupropion is generally thought to be a dopaminergic drug, nonetheless, i read somewhere that 's a partial agonist, meaning has both agonistic and antagonistic properties, thus blocking and enhancing dopamine at the same time; moreover, it was especially designed not to induce any "high" or pleasurable feeling. A few studies outlined the weak dopaminergic effect of the drug.
> > Can some of you guys relate to those findings at all? Or may be my dopamine receptors are to blame, possibly having been depleted by a long lasting anhedonia?
>
> Wellbutrin has a very narrow therapeutic range.
> It is actually a pro-drug (the parent compound
> bupropion is not involved much in the response, it
> is the metabolites, pricipally hydroxybupropion that
> are believed to do the work). The metabolites have
> a longer 1/2 life (like 20+ hrs for hydroxybupropion),
> and so they take a while to build up in your body and
> reach a steady state. Just a guess, but its possible you
> "passed through" the therapeutic window, maybe lowering the
> dosage would help.
>
> Some people believe that wellbutrin at really strong doses
> (metabolites above the thereapeutic range), actually indirectly
> increases the firing of serotonin neurons via an interaction
> between the increased Noradrenaline and serotonin.
>
> This is another off the wall hypothesis....
>
> One of the metabolites hydroxybupropion is believe to
> primarily be metabolized through the liver enzyme CYP 2D6.
> At very high levels I believe it may swamp that enzyme.
> I read a paper once suggesting that medicines that inhibit
> CYP 2D6 may cause EPS. I don't remember the working hypothesis
> though and it wasn't really substantiated (more of a guess).
> I should try to dig that one up.
>
> Just some wild guesses.
>
> Good Luck,
> John
This is from
"CYP 2d6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects"
Medical Hypothesis (1996) 47, 439-442
P. Vandel, B. Bonin, S. Vandel, D. Scheter, P. Bizouard
Quick and dirty summary:
- "The cyp 2d6 isoenzyme has been detected in the brain"
- "From animal data, there is evidence that cyp 26d is
involved in the metabolism of dopamine in the brain."
- "There is a genetically determined deficiency in cyp 2d6
and Parkinson's disease"
- examples of non psychiatric meds that inhibit 2d6 and
may induce dopamine related psychiatric illness. One med is
quinidine (a heart med).So there it is.
I would also like to note that about 1 in 20 caucasions
is a poor metabolizer of cyp 450 2d6. This means a drug
that needs it for a substrate can easily become toxic.
*Many* psychotropic meds use this enzyme of inhibit it.Curiously, few resistant patients are tested for poor
cyp 450 2d6 metabolism.John
Posted by Anna Laura on June 22, 2002, at 7:44:59
In reply to ok, here is the cyp2d6 dopamine hypothesis, posted by JohnX2 on June 21, 2002, at 0:58:12
> >
> > Wellbutrin has a very narrow therapeutic range.
> > It is actually a pro-drug (the parent compound
> > bupropion is not involved much in the response, it
> > is the metabolites, pricipally hydroxybupropion that
> > are believed to do the work). The metabolites have
> > a longer 1/2 life (like 20+ hrs for hydroxybupropion),
> > and so they take a while to build up in your body and
> > reach a steady state. Just a guess, but its possible you
> > "passed through" the therapeutic window, maybe lowering the
> > dosage would help.
> >
> > Some people believe that wellbutrin at really strong doses
> > (metabolites above the thereapeutic range), actually indirectly
> > increases the firing of serotonin neurons via an interaction
> > between the increased Noradrenaline and serotonin.
> >
> > This is another off the wall hypothesis....
> >
> > One of the metabolites hydroxybupropion is believe to
> > primarily be metabolized through the liver enzyme CYP 2D6.
> > At very high levels I believe it may swamp that enzyme.
> > I read a paper once suggesting that medicines that inhibit
> > CYP 2D6 may cause EPS. I don't remember the working hypothesis
> > though and it wasn't really substantiated (more of a guess).
> > I should try to dig that one up.
> >
> > Just some wild guesses.
> >
> > Good Luck,
> > John
>
>
> This is from
> "CYP 2d6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects"
> Medical Hypothesis (1996) 47, 439-442
> P. Vandel, B. Bonin, S. Vandel, D. Scheter, P. Bizouard
>
>
> Quick and dirty summary:
> - "The cyp 2d6 isoenzyme has been detected in the brain"
> - "From animal data, there is evidence that cyp 26d is
> involved in the metabolism of dopamine in the brain."
> - "There is a genetically determined deficiency in cyp 2d6
> and Parkinson's disease"
> - examples of non psychiatric meds that inhibit 2d6 and
> may induce dopamine related psychiatric illness. One med is
> quinidine (a heart med).
>
> So there it is.
>
> I would also like to note that about 1 in 20 caucasions
> is a poor metabolizer of cyp 450 2d6. This means a drug
> that needs it for a substrate can easily become toxic.
> *Many* psychotropic meds use this enzyme of inhibit it.
>
> Curiously, few resistant patients are tested for poor
> cyp 450 2d6 metabolism.
>
> John
Thanks for answering John,
I think i'm going to get screened for cyp 450 2d6 metabolism.
I have to take a SPECT with a dopaminergic "tracking" sometime soon; i'm going to have 2d6 checked too, i have nothing to loose anyway.
As far as Wellbutrin dosing is concerned i wouldn't hazard messing up with that .
I guess i'm going to wait a little longer (i'm on the third day of 450 mg. dose). Strangely, i feel kind of "sleepy": i get a weird mellow feeling; is far from being a "feeling good" sensation, but it's not bad either. It's somehow neutral, much like a benzo.
I recently called the Neuroscience University Clinic i've been at a couple of months ago; I went down there in mid April; after a few days of screening and interviewing they came up with a bipolar II dx, and suggested me to take a mood-stabilizer. When i called them back a couple of days ago they wondered why i haven't been prescribed for a mood stabilizer as they have been suggested;When i flied back home two months ago (the center is down South) i went to a local pdoc to get a prescription for Neurontin, but he wouldn't prescribe me that, stating that even though i had been hyperthymic for many years (had a "hypomanic phase" lasting a few months before crashing down and sinking in to depression ) i didn't run any serious risk of getting manic ; moreover, -he argued- i was apathetic/anhedonic,unmotivated and kind of slowed down, so i didn't need a mood stabilizer that was possibly going to put me down even further and sedate me;
Who's right? I don't know that yet. What would you suggest?
Posted by JohnX2 on June 22, 2002, at 17:19:06
In reply to Re: ok, here is the cyp2d6 dopamine hypothesis, posted by Anna Laura on June 22, 2002, at 7:44:59
Anna Laura,I think the most likely explanation of the EPS is
a drug interaction between Wellbutrin and Effexor.Although the 2d6 dopamine hypthesis may contribute
to this, I don't know how 2d6 inhibition affects
dopamine in the brain (still curious and looking
into that).There are alpha-1 (noradrenaline) recptors on
serotonin neurons in a part of the brain
(the noradrenaline diffuses over from a neighboring site).
These alpha-1 receptors increase the firing rate of the serotonin
neurons. This is part of Effexor's mode of action.
Wellbutrin also increases noradrenaline and it
could also contribute to the increased serotonin
action.Anyways usually serotonin hyperactivity has been
associated also with TD/EPS. Blockade of the
serotonin 5ht-2a receptor is usually an antidote.There also may be a problem with Wellbutrin inhibiting
the excretion of a Effexor chemical, but I don't know
too much about this. Its noted in the article I
posted below.I'll get back to you on the other questions....
John
Posted by LostBoyinNC1 on June 26, 2002, at 1:06:01
In reply to Wellbutrin extrapyramidal effects?, posted by Anna Laura on June 19, 2002, at 7:42:17
I never got any EPS symptoms from Wellbutrin SR when I took it years ago. However, I did get EPS type symptoms from Ritalin when I took that. Ritalin and Wellbutrin are kind of similar, with Ritalin being more potent of course. But I could see some people getting EPS type symptoms from Wellbutrin. With drugs...ANYTHING is possible.
On Ritalin, my muscles got tight and stiff feeling much the same as I get when I take atypical anti-psychotics. I dont know why.
Anything is possible on drugs, so if youve been on Wellbutrin for a while and are having stiff muscles and stuff like that, twitching and stuff, it would be time to tell your doctor about it.
Posted by Anna Laura on June 26, 2002, at 8:58:52
In reply to Re: Wellbutrin extrapyramidal effects?, posted by LostBoyinNC1 on June 26, 2002, at 1:06:01
> I never got any EPS symptoms from Wellbutrin SR when I took it years ago. However, I did get EPS type symptoms from Ritalin when I took that. Ritalin and Wellbutrin are kind of similar, with Ritalin being more potent of course. But I could see some people getting EPS type symptoms from Wellbutrin. With drugs...ANYTHING is possible.
>
> On Ritalin, my muscles got tight and stiff feeling much the same as I get when I take atypical anti-psychotics. I dont know why.
>
> Anything is possible on drugs, so if youve been on Wellbutrin for a while and are having stiff muscles and stuff like that, twitching and stuff, it would be time to tell your doctor about it.I don't have any stiff muscles and stuff like that
fortunately; my tongue keeps on twitching once in a while though.
I had a similar problem with Tofranil(imipramine); i usually get this twitching thing when the good effects of the drug are about to fade away : when the twitching goes away, the good effects also desappear .
P.S.I called my pdoc but he didn't return my calls.
Posted by JohnX2 on June 26, 2002, at 18:37:53
In reply to Re: Wellbutrin extrapyramidal effects? LostBoy, posted by Anna Laura on June 26, 2002, at 8:58:52
> > I never got any EPS symptoms from Wellbutrin SR when I took it years ago. However, I did get EPS type symptoms from Ritalin when I took that. Ritalin and Wellbutrin are kind of similar, with Ritalin being more potent of course. But I could see some people getting EPS type symptoms from Wellbutrin. With drugs...ANYTHING is possible.
> >
> > On Ritalin, my muscles got tight and stiff feeling much the same as I get when I take atypical anti-psychotics. I dont know why.
> >
> > Anything is possible on drugs, so if youve been on Wellbutrin for a while and are having stiff muscles and stuff like that, twitching and stuff, it would be time to tell your doctor about it.
>
>
>
> I don't have any stiff muscles and stuff like that
> fortunately; my tongue keeps on twitching once in a while though.
> I had a similar problem with Tofranil(imipramine); i usually get this twitching thing when the good effects of the drug are about to fade away : when the twitching goes away, the good effects also desappear .
>
>
> P.S.
>
> I called my pdoc but he didn't return my calls.That paper on 2d6 phenotype hypothesis of ad extrapyramidal effects
lists a few references:1. A case of oral dyskinesia associated with
imipramine treatment. Am J Psy. 1977; 134 (11) 1297-12982. Desipramine induced oral-pharyngeal disturbances:
stutterting and jaw mycoclonus. J Clin Psychopharm
1992; 12(6): 44-45A bunch more on tricyclics... (2d6 meds).
John
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