Posted by JohnX2 on March 5, 2002, at 18:28:30
In reply to Re: Switching to Celexa/maybe Wellbutrin? » maribeth, posted by JohnX2 on March 5, 2002, at 18:09:19
Prozac potently inhibits CYP450-2D6.
Sorry if my cut and paste stinks.Here was a medline abstract I saw discussing
this hydroxybupropion accumulation phenomina:Bupropion plasma levels and CYP2D6 phenotype.
Ther Drug Monit 1996 Oct;18(5):581-5 (ISSN: 0163-4356)
Pollock BG; Sweet RA; Kirshner M; Reynolds CF
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, USA.
All available antidepressants with the exception of fluvoxamine and nefazodone either are metabolized by
cytochrome P450 2D6 (CYP2D6) and/or inhibit this isozyme. To date, nothing in this regard has been
published concerning bupropion. We report that plasma level/dose ratios for bupropion, and its
metabolites erythrohydrobupropion and threohydrobupropion, were not associated with debrisoquine
metabolic status in 12 patients, three of whom were poor 2D6 metabolizers. The plasma level/dose
ratios for the metabolite hydroxybupropion were, however, significantly higher in poor 2D6 metabolizers.
In three patients, who received a second phenotyping test during treatment with bupropion, debrisoquine
metabolic ratios were not increased. It is thus inferred that bupropion is neither metabolized by nor
inhibits CYP2D6. The potential accumulation of hydroxybupropion after CYP2D6 inhibition may, however,
contribute to toxicity and impair bupropion's therapeutic effectiveness.
Major Subject Heading(s)
Minor Subject Heading(s)
CAS Registry / EC Numbers
Antidepressive Agents,
Second-Generation [blood]
Bupropion [blood]
Cytochrome P-450 CYP2D6
[genetics]
Depressive Disorder [blood]
[enzymology]
Aged
Bupropion [administration &
dosage] [adverse effects]
Depressive Disorder [drug
therapy]
Dose-Response
Relationship, Drug
Phenotype
Seizures [chemically induced]
0 (Antidepressive Agents,
Second-Generation)
34841-39-9 (Bupropion)
EC 1.14.99.- (Cytochrome
P-450 CYP2D6)Indexing Check Tags: Female; Human; Male; Support, U.S. Gov't, P.H.S.
Language: English
MEDLINE Indexing Date: 199703
Publication Type: Status: Completed
Publication Type: Clinical Trial; Journal Article
Grant ID: MH 01040; MH 01153; MH 43832; , etc.
PreMedline Identifier: 0008885123
Unique NLM Identifier: 97039571
Journal Code: IM>
> Hi,
>
> Wellbutrin has a very narrow therapeutic dosing
> window, and so your pdoc may be right that if you
> go slower with the anti-psychotic medicine in place
> then odds are you won't have the psychotic episode.
>
> Also dexedrine is a potent dopaminergic medicine
> which can induce a psychosis by itself over time.
> The combo could have just sent you over the tilt.
>
> Here is a possible prozac interaction that may
> have caused a problem. It has to do with inhibition
> of the liver enzyme cyp450-2d6. I
> have seen conflicting data on this but it could
> explain wellbutrin reaching toxic levels with
> Prozac. One of wellbutrin's more potent metabolites
> (hydroxybupropion) does a lot of work for the medicine.
> I.e. the main medicine bupropion gets broken up by your
> liver into a few metablites (little "sub-medicines"), and
> these metabolites are thought to be psychoactive. Its my
> understanding, and I see a lot of conflicting info for
> wellbutrin, but its generally the case that these
> hyrdroxy-blah-blah chemicals need to be deactivated in
> the liver using the cyp450-2d6 enzyme. But prozac
> is known to POTENTLY inhibit the production of that
> liver enzyme. So its possible, just a thought, that the
> prozac was causing the wellbutrin to reach toxic levels
> in your system. I don't think celexa goes down
> that liver route, and don't know about seroquel.
> Another issue is that 1 in 20 cuacasions is a poor
> metabolizer of cyp450-2d6 medicines in general.
>
> But what happened on the last pschotic trip?
> How did they treat it at the hospital? Did they
> put you onto an anti-psychotic medication at the
> time?
>
> Anyways, how would you describe "the quality of
> life" improving on wellbutrin. People who become
> manic and then psychotic got lots of dopamine running
> through their body and this can make them feel real
> good. Or were you feeling something else?
> Ever had diagnosis of manic/hypomania in the past?
> Any family history of bipolar?
>
> just a few thoughts. Hope it is not too
> technical.
>
> -John
>
>
> > Hi Y'all
> > It has been awhile since I have posted here, but things have been going well. I have been on Effexor XR which my pdoc has me coming off of while - I slowly work up to Celexa. (Current Eff is 150mgm-- current Celexa -- 15mgm.) He expects me to end up on 30 or 40mg of Celexa. I was on 325mgm Effexor at tops. He tells me that if the Celexa doesnt do the trick, we will either add or switch to Wellbutrin.
> > Now here is the screamer.----
> > Three and a half years ago I was put on Wellbutrin SR 150mgm bid (unsure of dose-red pill) to take the place of Ritalin. It worked wonderfully, for about 48hours, then I got very delusionally psycotic and spent four or five days in the seclusion room at the local Univ. Hosp Psych ward. I was also on Prozac 30mgm at the time, I had taken 10mgm of dexadrine (from a friend) the day before, the Wellb. took about a week to work -but WHILE it worked it qave me a quality of life unlike anything I have ever known. My pdoc knows about all of the above and says not to worry, we would go slowly and use smaller doses. Besides, he tells me, since I now take Seroquel 400mgm daily that would "protect"
> > me from the psycosis.
> > I would really like to hear from some of you. The thought that maybe I COULD benefit and have what I did have for that brief time IS SO TEMPTING. However, the fear of that horrible time that came right after (I do not remember only the very beginning)is still with me.
> > I was diagnosed ADD Many years ago, (1986) long before it was really noticed in adults. I was put on Ritalin. This was possible mostly because I worked in the same institution as my therapist and prescribing pdoc. It worked wonders, but my husband refuses to allow any "controlled substances")
> > I am 59 now and had almost forgotten what the "focused life" was like! Is it possible that after all of these years there is an answer? Will being on the Seroquel really "protect" me from the psychosis? Was the psychotic episode due to the Dexedrine? (my husband's theory) How much Celexa must I take to "equal" the 325mgm of EffexorXR? PLEASE SHARE YOUR WISDOM WITH ME!! maribeth
> > PS I am getting off the Effexor due to weight
> > gain -- 30lb in 2 years!
poster:JohnX2
thread:96340
URL: http://www.dr-bob.org/babble/20020301/msgs/96589.html