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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by yeltom on November 16, 2004, at 2:15:46
I've been on prozac or celexa for depression, anxiety, and OCD for quite a while. Have tried various ways of augmenting it with something to help with apathy, anhedonia, fatigue, etc. I also recently had some issues with IBS, and when my gastro doctor recommended a tricyclic, I spoke with my shrink and settled on nortriptyline. I figured I'd kill two birds with one stone. First I was on 40 mg celexa and 10 mg nortrip. Tried to up to 20 mg but couldn't handle it. 10 mg seemed to be remarkably effective. Then I switched back to 40 mg prozac for financial reasons, and I started suffering from dry mouth and bad constipation. So I hypothesized that prozac was inhibiting that enzyme that metabolizes nortrip and I dropped to 5 mg nortrip. (Have to open the stupid capsules because 10 mg is smallest amount) I'm just wondering if it would seem absurd that 5 mg of nortrip could be causing significant norepinephrine boost. It's definitely helping with the IBS, but it seems to be helping with mood too, but I'm wondering if that must be a placebo effect at such a low dose. When I tried strattera with prozac, I couldn't even handle 18 mg without bad constipation. Does this suggest that I'm very sensitive to that liver-enzyme suppression thing? I've heard that prozac causes serum levels of TCAs to at least double. But it would seem to be doing a lot more than doubling it, considering that you usually need at least 50 mg of nortrip for antidepressant effect. Is enzyme-inhibiting effect of prozac dose-dependent? Any reason to try lowering prozac and increasing nortrip? Thanks.
Posted by Sad Panda on November 16, 2004, at 5:05:33
In reply to prozac + nortripyline pharmacology questions, posted by yeltom on November 16, 2004, at 2:15:46
> I've been on prozac or celexa for depression, anxiety, and OCD for quite a while. Have tried various ways of augmenting it with something to help with apathy, anhedonia, fatigue, etc. I also recently had some issues with IBS, and when my gastro doctor recommended a tricyclic, I spoke with my shrink and settled on nortriptyline. I figured I'd kill two birds with one stone. First I was on 40 mg celexa and 10 mg nortrip. Tried to up to 20 mg but couldn't handle it. 10 mg seemed to be remarkably effective. Then I switched back to 40 mg prozac for financial reasons, and I started suffering from dry mouth and bad constipation. So I hypothesized that prozac was inhibiting that enzyme that metabolizes nortrip and I dropped to 5 mg nortrip. (Have to open the stupid capsules because 10 mg is smallest amount) I'm just wondering if it would seem absurd that 5 mg of nortrip could be causing significant norepinephrine boost. It's definitely helping with the IBS, but it seems to be helping with mood too, but I'm wondering if that must be a placebo effect at such a low dose. When I tried strattera with prozac, I couldn't even handle 18 mg without bad constipation. Does this suggest that I'm very sensitive to that liver-enzyme suppression thing? I've heard that prozac causes serum levels of TCAs to at least double. But it would seem to be doing a lot more than doubling it, considering that you usually need at least 50 mg of nortrip for antidepressant effect. Is enzyme-inhibiting effect of prozac dose-dependent? Any reason to try lowering prozac and increasing nortrip? Thanks.
>
>
>Prozac & Paxil are potent inhibitors of CYP 2D6 & will increase the plasma level of Nortriptyline by alot.(up to 9x for some drugs) 2D6 is also subject to the most genetic variation & I would think that you are a poor metabolizer of drugs using 2D6, as are about 10% of the population because 10mg is a very small doseage. Blood testing is the best way to go with Nort because the most is known about it & it said that 50 to 150 ng/ml is the best level.
Cheers,
Paul.
Posted by darkhorse on November 16, 2004, at 6:52:06
In reply to prozac + nortripyline pharmacology questions, posted by yeltom on November 16, 2004, at 2:15:46
> I've been on prozac or celexa for depression, anxiety, and OCD for quite a while. Have tried various ways of augmenting it with something to help with apathy, anhedonia, fatigue, etc. I also recently had some issues with IBS, and when my gastro doctor recommended a tricyclic, I spoke with my shrink and settled on nortriptyline. I figured I'd kill two birds with one stone. First I was on 40 mg celexa and 10 mg nortrip. Tried to up to 20 mg but couldn't handle it. 10 mg seemed to be remarkably effective. Then I switched back to 40 mg prozac for financial reasons, and I started suffering from dry mouth and bad constipation. So I hypothesized that prozac was inhibiting that enzyme that metabolizes nortrip and I dropped to 5 mg nortrip. (Have to open the stupid capsules because 10 mg is smallest amount) I'm just wondering if it would seem absurd that 5 mg of nortrip could be causing significant norepinephrine boost. It's definitely helping with the IBS, but it seems to be helping with mood too, but I'm wondering if that must be a placebo effect at such a low dose. When I tried strattera with prozac, I couldn't even handle 18 mg without bad constipation. Does this suggest that I'm very sensitive to that liver-enzyme suppression thing? I've heard that prozac causes serum levels of TCAs to at least double. But it would seem to be doing a lot more than doubling it, considering that you usually need at least 50 mg of nortrip for antidepressant effect. Is enzyme-inhibiting effect of prozac dose-dependent? Any reason to try lowering prozac and increasing nortrip? Thanks.
Hello,
I also tried prozac 20 + nort 25 and had very very bad reaction....but I also tried amitriptyline 25-50,and later imipramine 25mg with prozac which was OK....so I guess some people are poor metabolizer,and nort in particular along with desipramine are metabolized only by 2d6...so for poor metabolizer, one must be very cautious adding nort to either prozac or seroxat/paxil.Adam
Posted by King Vultan on November 16, 2004, at 9:08:47
In reply to prozac + nortripyline pharmacology questions, posted by yeltom on November 16, 2004, at 2:15:46
Prozac is one of the more notorious inhibitors of the 2D6 enzyme among the SSRIs, along with Paxil. As Panda indicates, the concentration of another 2D6 substrate, such as nortriptyline, can be increased many fold, and this is true even in a person with normal levels of the 2D6 enzyme (these people are referred to as extensive metabolizers, as compared to poor metabolizers, who are deficient in the enzyme). I would recommend getting your blood plasma level of the nortriptyline checked to see if it is in the therapeutic range. I suffered from constipation and dry mouth myself on as little as 50 mg of nortriptyline taken my itself, and I am an extensive metabolizer of the 2D6 enzyme.
The type of interaction you are seeing is the reason for the cautionary statements in such references as the PDR (Physician's Desk Reference) about mixing SSRIs and tricylics. People have unwittingly gone into overdose or near overdose states on a tricyclic when combining one with an SSRI and not taking this enzyme interaction into account. My opinion is that people should always have their blood plasma level of the tricyclic monitored when they are on one, regardless of whether they take one by itself or with something else.
Todd
Posted by Sad Panda on November 16, 2004, at 9:49:14
In reply to Re: prozac + nortripyline pharmacology questions, posted by King Vultan on November 16, 2004, at 9:08:47
This PubMed extract demonstrates how bad Prozac is.
"Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe.
Amchin J, Ereshefsky L, Zarycranski W, Taylor K, Albano D, Klockowski PM.
Wyeth-Ayerst Laboratories, 240 North Radnor-Chester Road, St. Davids, PA 19087, USA.
Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e., DM:DT) excreted in urine after DM coadministration. Twenty-eight healthy extensive metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7 days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26 completed the study. Plasma concentrations of both drugs and their active metabolites were determined. DM:DTs were evaluated at baseline (Day 0), on Days 7 and 28 of dosing, and 2 weeks after drug discontinuation (Day 42). Steady-state drug and metabolite levels were achieved in both groups by Day 28. Mean DM:DTs for venlafaxine and fluoxetine differed statistically significantly (p < 0.001) on Days 7, 28, and 42. Comparisons of DM:DT as a percentage of baseline values showed that DM:DT increased 1.2-fold for venlafaxine and 9.1-fold for fluoxetine on Day 7 (p < 0.001) and increased 2.1-fold for venlafaxine and 17.1-fold for fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2 weeks after discontinuation of fluoxetine, unlike the case with venlafaxine. These in vivo results confirm in vitro data demonstrating significantly weaker inhibition of CYP2D6 with venlafaxine than with fluoxetine. This suggests that clinically significant interactions involving CYP2D6 inhibition could occur between fluoxetine and drugs metabolized by CYP2D6 but may be less likely to occur with venlafaxine."
There are a couple of posters here who use Prozac to boost Effexor levels, this is a very dangerous comination for the majority of people, but is fine for ultra fast 2D6 metabolizers. I consider myself to be an average metabolizer of drugs that use 2D6 & have combined 150 mg of Effexor with 125+mg of Nortriptyline. It's worth noting that I find codiene relatively useless these days as it uses 2D6 too.Cheers,
Paul.
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