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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by KaraS on November 3, 2004, at 22:44:55
Any reason not to combine these two medications?
Posted by King Vultan on November 3, 2004, at 23:08:58
In reply to Wellbutrin + Paxil?, posted by KaraS on November 3, 2004, at 22:44:55
> Any reason not to combine these two medications?
>
>
>
Yes, they're both strong CYP-450 2D6 inhibitors and also substrates of that enzyme (you will not see Wellbutrin listed on every enzyme interaction chart, perhaps because its metabolites are the real problem). Each drug will tend to increase the blood plasma level of the other substantially. While there would not be the lethality concerns in the same sense there would be if one of the drugs were a tricyclic, a person would run some risk of excessive side effects from one or both. Actually, if a tricyclic were involved, you could at least monitor blood plasma levels to see if they were in the therapeutic range, and adjust the dosage accordingly. With Wellbutrin and Paxil, I think a person would be very much in the dark as to what is really going on.Todd
Posted by KaraS on November 3, 2004, at 23:56:58
In reply to Re: Wellbutrin + Paxil?, posted by King Vultan on November 3, 2004, at 23:08:58
> > Any reason not to combine these two medications?
> >
> >
> >
>
>
> Yes, they're both strong CYP-450 2D6 inhibitors and also substrates of that enzyme (you will not see Wellbutrin listed on every enzyme interaction chart, perhaps because its metabolites are the real problem). Each drug will tend to increase the blood plasma level of the other substantially. While there would not be the lethality concerns in the same sense there would be if one of the drugs were a tricyclic, a person would run some risk of excessive side effects from one or both. Actually, if a tricyclic were involved, you could at least monitor blood plasma levels to see if they were in the therapeutic range, and adjust the dosage accordingly. With Wellbutrin and Paxil, I think a person would be very much in the dark as to what is really going on.
>
> Todd
>
>Todd,
I had a feeling I was going to get that response - but doesn't the same apply to Effexor and that is always used together with Wellbutrin?K
Posted by SLS on November 4, 2004, at 6:17:19
In reply to Re: Wellbutrin + Paxil? » King Vultan, posted by KaraS on November 3, 2004, at 23:56:58
Hi Kara.
Wellbutrin (bupropion) itself is increased by the inhibition of 2B6 by Paxil (not 2D6). Wellbutrin is a weak inhibitor of 2D6, but not a substrate. As Todd indicates, the major metabolite of Wellbutrin, 2-hydroxybupropion is affected by Paxil. It is increased due to the action of Paxil at both 2D6 and 2B6. It is pharmacology active, and thought by some as being more responsible than the parent compound for the therapeutic effect of Wellbutrin. Unfortunately, the seizure risk of Wellbutrin, although generally exaggerated, must still be taken into consideration. I was fine at a dosage of 900mg.
Effexor + Wellbutrin is without these interactions and will not result in increased levels of either drug.
Do you obtain a partial response to either Paxil or Effexor?
- Scott
Posted by Optimist on November 4, 2004, at 7:18:47
In reply to Re: Wellbutrin + Paxil? » KaraS, posted by SLS on November 4, 2004, at 6:17:19
Does the same thing occur with Wellbutrin and Prozac?
Posted by SLS on November 4, 2004, at 7:26:56
In reply to Re: Wellbutrin + Prozac King Vultan/? » SLS, posted by Optimist on November 4, 2004, at 7:18:47
> Does the same thing occur with Wellbutrin and Prozac?
Levels of Wellbutrin are increased moderately by Prozac. I doubt there would be a problem if you don't go over 300mg a day.
- Scott
Posted by SLS on November 4, 2004, at 7:28:03
In reply to Re: Wellbutrin + Paxil?, posted by King Vultan on November 3, 2004, at 23:08:58
Good catch, Todd.
- Scott
Posted by theo on November 4, 2004, at 7:30:17
In reply to Wellbutrin + Paxil?, posted by KaraS on November 3, 2004, at 22:44:55
From what I've researched, there is more concern takin Prozac/Wellbutrin than Paxil/Wellbutrin. I've taken both combos, Wellbutrin was mainly added when it was suppose to be a big help with SSRI sexual dsyfunction, which by the way did nothing for me in that department.
I had no dangerous side effects and dropped one or the other because I have high anxiety and taking a SSRI/Wellbutrin combo was a bit much for me on the anxiety issues.
Posted by King Vultan on November 4, 2004, at 11:05:05
In reply to Re: Wellbutrin + Paxil? » KaraS, posted by SLS on November 4, 2004, at 6:17:19
I perhaps do worry too much about these CYP-450 interactions, but I have read anecdotes in which people were taking, for instance, Prozac + desipramine, and were in near overdose states of the tricyclic without understanding what was going on. Obviously, there isn't nearly the concern when dealing with non-tricyclics, but since I've been on Wellbutrin combined with various drugs myself, I've done a lot of research on it.
The truth is that the best info on Wellbutrin's ability to inhibit other 2D6 metabolized drugs comes right with it in the prescribing info. "In a study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of the CYP2D6 enzyme, daily doses of bupropion given at 150 mg twice daily followed by a single 50 mg dose of desipramine increased the Cmax, AUC, and t 1/2 of desipramine by an average of two-, five-, and two-fold respectively." So it would appear that 300 mg/day of Wellbutrin can easily double (or more, also considering the AUC--area underneath the curve) the blood plasma level of drugs that are mainly metabolized by 2D6. How much does this matter if that drug is an SSRI? I don't know, probably not that much, but one would think that side effects would at least tend to increase somewhat, and it is something to be aware of.
Todd
Posted by KaraS on November 4, 2004, at 15:39:53
In reply to Re: Wellbutrin + Paxil? » KaraS, posted by SLS on November 4, 2004, at 6:17:19
> Hi Kara.
>
> Wellbutrin (bupropion) itself is increased by the inhibition of 2B6 by Paxil (not 2D6). Wellbutrin is a weak inhibitor of 2D6, but not a substrate. As Todd indicates, the major metabolite of Wellbutrin, 2-hydroxybupropion is affected by Paxil. It is increased due to the action of Paxil at both 2D6 and 2B6. It is pharmacology active, and thought by some as being more responsible than the parent compound for the therapeutic effect of Wellbutrin. Unfortunately, the seizure risk of Wellbutrin, although generally exaggerated, must still be taken into consideration. I was fine at a dosage of 900mg.
>
> Effexor + Wellbutrin is without these interactions and will not result in increased levels of either drug.
>
> Do you obtain a partial response to either Paxil or Effexor?
>
>
> - Scott
Thanks, Scott. This info was for a friend of mine on Wellbutrin. He is responding partially to it (perhaps as much as 50%). I'm trying to convince him to augment it rather than give up and try an SSRI - esp. since he has an anergic depression. He also has problems with GAD. My friend has not tried Effexor yet. He tried Paxil in the past but for many reasons thinks that he didn't give it an adequate trial. I hope he doesn't quit the Wellbutrin and try Paxil again.Kara
Posted by KaraS on November 4, 2004, at 15:45:47
In reply to Re: Wellbutrin + Paxil? » KaraS, posted by theo on November 4, 2004, at 7:30:17
> From what I've researched, there is more concern takin Prozac/Wellbutrin than Paxil/Wellbutrin. I've taken both combos, Wellbutrin was mainly added when it was suppose to be a big help with SSRI sexual dsyfunction, which by the way did nothing for me in that department.
>
> I had no dangerous side effects and dropped one or the other because I have high anxiety and taking a SSRI/Wellbutrin combo was a bit much for me on the anxiety issues.
Theo,Aren't SSRIs usually good for anxiety? Maybe the high anxiety you experienced was because of increased concentration of Wellbutrin due to the addition of Prozac or Paxil?
Kara
Posted by KaraS on November 4, 2004, at 16:01:26
In reply to Re: Wellbutrin + Paxil? » King Vultan, posted by SLS on November 4, 2004, at 7:28:03
> Good catch, Todd.
>
>
> - Scott
Yes, Thanks Todd. You're always so helpful!Kara
Posted by jujube on November 6, 2004, at 13:54:27
In reply to Re: Wellbutrin + Paxil? » SLS, posted by King Vultan on November 4, 2004, at 11:05:05
Would the same concern apply to a combination of Anafranil and Celexa? My pdoc just prescribed Anafranil and has told me to reduce my dose of Celexa to 20 mg (from 40 mg) and continue to use it at the same time as the Anafranil. I have never taken 2 ADs at the same time, so I have been a bit worried about this.
Thanks.
Tamara
> I perhaps do worry too much about these CYP-450 interactions, but I have read anecdotes in which people were taking, for instance, Prozac + desipramine, and were in near overdose states of the tricyclic without understanding what was going on. Obviously, there isn't nearly the concern when dealing with non-tricyclics, but since I've been on Wellbutrin combined with various drugs myself, I've done a lot of research on it.
>
> The truth is that the best info on Wellbutrin's ability to inhibit other 2D6 metabolized drugs comes right with it in the prescribing info. "In a study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of the CYP2D6 enzyme, daily doses of bupropion given at 150 mg twice daily followed by a single 50 mg dose of desipramine increased the Cmax, AUC, and t 1/2 of desipramine by an average of two-, five-, and two-fold respectively." So it would appear that 300 mg/day of Wellbutrin can easily double (or more, also considering the AUC--area underneath the curve) the blood plasma level of drugs that are mainly metabolized by 2D6. How much does this matter if that drug is an SSRI? I don't know, probably not that much, but one would think that side effects would at least tend to increase somewhat, and it is something to be aware of.
>
> Todd
Posted by King Vultan on November 6, 2004, at 22:58:18
In reply to Re: Wellbutrin + Paxil? » King Vultan, posted by jujube on November 6, 2004, at 13:54:27
> Would the same concern apply to a combination of Anafranil and Celexa? My pdoc just prescribed Anafranil and has told me to reduce my dose of Celexa to 20 mg (from 40 mg) and continue to use it at the same time as the Anafranil. I have never taken 2 ADs at the same time, so I have been a bit worried about this.
>
> Thanks.
>
> Tamara
>
>
Not exactly, because the enzyme interactions between these two drugs are pretty limited. Celexa is only a weak 2D6 inhibitor and is not going to increase the blood plasma levels of the Anafranil appreciably. The only thing I would question is why your pdoc is having you take two SSRIs at once (Anafranil/clomipramine is a tricylic AD, but it is also an SSRI, as it is selective for blocking serotonin reuptake). Was any reasoning given for this?
Todd
Posted by jujube on November 7, 2004, at 7:20:46
In reply to Re: Wellbutrin + Paxil? » jujube, posted by King Vultan on November 6, 2004, at 22:58:18
> > Would the same concern apply to a combination of Anafranil and Celexa? My pdoc just prescribed Anafranil and has told me to reduce my dose of Celexa to 20 mg (from 40 mg) and continue to use it at the same time as the Anafranil. I have never taken 2 ADs at the same time, so I have been a bit worried about this.
> >
> > Thanks.
> >
> > Tamara
> >
> >
>
>
> Not exactly, because the enzyme interactions between these two drugs are pretty limited. Celexa is only a weak 2D6 inhibitor and is not going to increase the blood plasma levels of the Anafranil appreciably. The only thing I would question is why your pdoc is having you take two SSRIs at once (Anafranil/clomipramine is a tricylic AD, but it is also an SSRI, as it is selective for blocking serotonin reuptake). Was any reasoning given for this?
>
> ToddThanks. The pdoc did not say why he wants me to continue the Celexa. I would imagine that it will be a short-term thing, until I get up to a therapeutic dose of the Anafranil.
Tamara
Posted by ed_uk on November 7, 2004, at 7:21:45
In reply to Re: Wellbutrin + Paxil? » jujube, posted by King Vultan on November 6, 2004, at 22:58:18
> > Would the same concern apply to a combination of Anafranil and Celexa? My pdoc just prescribed Anafranil and has told me to reduce my dose of Celexa to 20 mg (from 40 mg) and continue to use it at the same time as the Anafranil. I have never taken 2 ADs at the same time, so I have been a bit worried about this.
> >
> > Thanks.
> >
> > Tamara
> >
> >
>
>
> Not exactly, because the enzyme interactions between these two drugs are pretty limited. Celexa is only a weak 2D6 inhibitor and is not going to increase the blood plasma levels of the Anafranil appreciably. The only thing I would question is why your pdoc is having you take two SSRIs at once (Anafranil/clomipramine is a tricylic AD, but it is also an SSRI, as it is selective for blocking serotonin reuptake). Was any reasoning given for this?
>
> Todd
Hello it's Ed! I was thinking exactly the same thing as Todd... I expect the reason for continuing the Celexa at 20mg/day is probably to help prevent withdrawal symptoms from the celexa while the Anafranil dose is still low. Since Anafranil also inhibits the reuptake of serotonin, you shouldn't get any major withdrawal symptoms from the Celexa. Once the Anafranil dose has been increased to a decent level it would make sense to stop the Celexa completely.
Although the clomipramine molecule itself is a potent (selective) serotonin reuptake inhibitor, its major active metabolite is a norepinephrine reuptake inhibitor. Clomipramine also blocks certain serotonin receptors, all these properties give the Anafranil a good chance of helping your depression when Celexa hasn't. If Anafranil doesn't suit you, nortriptyline or desipramine could be next on your list.
As Todd said, the pharmacokinetic interaction between citalopram and TCAs is much less significant than it is with Paxil.From Stockleys drug interactions...
.....'5 patients on amitriptyline, clomipramine or maprotiline showed no changes in their plasma tricyclic antidepressant levels when 20 to 60mg citalopram daily was added'.....
.......'In another general study, in which 18 patients were given citalopram and tricyclic antidepressants, serum levels of citalopram were doubled in those receiving the tricyclic clomipramine'.... A good reason to halve your Celexa dose, what do you think??!!All the best..
Ed.
Posted by jujube on November 7, 2004, at 7:28:00
In reply to Re: Wellbutrin + Paxil?, posted by ed_uk on November 7, 2004, at 7:21:45
> > > Would the same concern apply to a combination of Anafranil and Celexa? My pdoc just prescribed Anafranil and has told me to reduce my dose of Celexa to 20 mg (from 40 mg) and continue to use it at the same time as the Anafranil. I have never taken 2 ADs at the same time, so I have been a bit worried about this.
> > >
> > > Thanks.
> > >
> > > Tamara
> > >
> > >
> >
> >
> > Not exactly, because the enzyme interactions between these two drugs are pretty limited. Celexa is only a weak 2D6 inhibitor and is not going to increase the blood plasma levels of the Anafranil appreciably. The only thing I would question is why your pdoc is having you take two SSRIs at once (Anafranil/clomipramine is a tricylic AD, but it is also an SSRI, as it is selective for blocking serotonin reuptake). Was any reasoning given for this?
> >
> > Todd
>
>
> Hello it's Ed! I was thinking exactly the same thing as Todd... I expect the reason for continuing the Celexa at 20mg/day is probably to help prevent withdrawal symptoms from the celexa while the Anafranil dose is still low. Since Anafranil also inhibits the reuptake of serotonin, you shouldn't get any major withdrawal symptoms from the Celexa. Once the Anafranil dose has been increased to a decent level it would make sense to stop the Celexa completely.
> Although the clomipramine molecule itself is a potent (selective) serotonin reuptake inhibitor, its major active metabolite is a norepinephrine reuptake inhibitor. Clomipramine also blocks certain serotonin receptors, all these properties give the Anafranil a good chance of helping your depression when Celexa hasn't. If Anafranil doesn't suit you, nortriptyline or desipramine could be next on your list.
> As Todd said, the pharmacokinetic interaction between citalopram and TCAs is much less significant than it is with Paxil.
>
> From Stockleys drug interactions...
> .....'5 patients on amitriptyline, clomipramine or maprotiline showed no changes in their plasma tricyclic antidepressant levels when 20 to 60mg citalopram daily was added'.....
> .......'In another general study, in which 18 patients were given citalopram and tricyclic antidepressants, serum levels of citalopram were doubled in those receiving the tricyclic clomipramine'.... A good reason to halve your Celexa dose, what do you think??!!
>
> All the best..
> Ed.Ed,
Yup, makes sense to me. Thanks for the info. I appreciate it.
Take care.
Tamara
Posted by theo on November 7, 2004, at 7:53:51
In reply to Re: Wellbutrin + Paxil? » theo, posted by KaraS on November 4, 2004, at 15:45:47
> > From what I've researched, there is more concern takin Prozac/Wellbutrin than Paxil/Wellbutrin. I've taken both combos, Wellbutrin was mainly added when it was suppose to be a big help with SSRI sexual dsyfunction, which by the way did nothing for me in that department.
> >
> > I had no dangerous side effects and dropped one or the other because I have high anxiety and taking a SSRI/Wellbutrin combo was a bit much for me on the anxiety issues.
>
>
> Theo,
>
> Aren't SSRIs usually good for anxiety? Maybe the high anxiety you experienced was because of increased concentration of Wellbutrin due to the addition of Prozac or Paxil?
>
> Kara
>
Kara,Paxil is the only SSRI I've taken that really works for anxiety. I could tolerate the Wellbutrin with Paxil but it didn't improve anything, just added the classic Wellbutrin side effects, headache and ears ringing.
Prozac is activating and in my opinion does nothing for anxiety. It may make you more aggressive which may seem more pro active, but that can backfire. Prozac/Wellbutrin combo needless to say was a disaster for me, anxiety central.
Posted by Emily Elizabeth on November 7, 2004, at 8:53:39
In reply to Re: Wellbutrin + Paxil?, posted by ed_uk on November 7, 2004, at 7:21:45
Do you have access to Stockley's Drug Interactions? I'm on Lexapro and Desipramine. My pdoc says it seems like my blood plasma levels of the desipramine don't seem to be effected by the Lex. I'm wondering if this is consistent with other findings? Seen anything on it?
Thanks,
EE>
> From Stockleys drug interactions...
> .....'5 patients on amitriptyline, clomipramine or maprotiline showed no changes in their plasma tricyclic antidepressant levels when 20 to 60mg citalopram daily was added'.....
> .......'In another general study, in which 18 patients were given citalopram and tricyclic antidepressants, serum levels of citalopram were doubled in those receiving the tricyclic clomipramine'.... A good reason to halve your Celexa dose, what do you think??!!
>
> All the best..
> Ed.
Posted by ed_uk on November 7, 2004, at 10:12:18
In reply to Question for Ed, posted by Emily Elizabeth on November 7, 2004, at 8:53:39
Yes, I've got Stockleys...
Escitalopram isn't in the textbook yet because it's too new. The interactions of escitalopram are believed to be the same as the interactions of citalopram. Here is what it says about citalopram and desipramine:Citalopram caused an approximately 50% increase in the AUC of desipramine (the primary metabolite of imipramine) after a single 100mg oral dose of imipramine, and a reduction in the levels of the subsequently formed metabolite of desipramine.
Here is what the Medicines Compendium says...
Effect of escitalopram(Lexapro/Cipralex) on the pharmacokinetics of other medicinal products
Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when escitalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as ***desipramine***, clomipramine and nortryptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.
Overall, I think plasma level monitoring could be a good idea, especially if you're taking a high dose of desipramine. Alternatively, you could ask for an electrocardiogram- to examine the effect of desipramine on the electrical activity of your heart.
All the best...
Ed
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