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SSRI + TCA Interaction (isozyme P450 2D6)

Posted by rod on December 27, 2001, at 7:01:51

In reply to Re: Low Dose (~20 mg) Anafranil ??, posted by edward602 on December 25, 2001, at 15:19:12

Now I know, why I felt bad on Prozac + Elavil (both full dose) and why my current med combo Celexa + Anafranil is not good.So I might be right taking Anafranil at a very low dosage. My Doctor is a JERK!

http://www.rxlist.com/cgi/generic/clomipr_ad.htm

excerpt:

Drugs Metabolized by P450 2D6: The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7%-10% of Caucasians are so-called ?poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhabit the activity of this isozyme and make normal metabolizers resemble p.o. metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine: cimetidine) and many that are substrates for P450 2D6 (many other antidepressants phenothiazines and the Type 1C antiarrythmics propafenone and flecainide) while all the selective serotonin reuptake inhibitors (SSRIs), e.g fluoxetine, sertraline, and paroxetine, inhabit P450 2D6. They may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of T.A. with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.


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poster:rod thread:87847
URL: http://www.dr-bob.org/babble/20011222/msgs/87933.html