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
poster:JohnX2
thread:110261
URL: http://www.dr-bob.org/babble/20020617/msgs/110381.html