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
poster:JohnX2
thread:110261
URL: http://www.dr-bob.org/babble/20020617/msgs/110382.html