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Re: Experiences w/ switching from SSRI to tricyclic? » Jane D

Posted by Cam W. on September 20, 2001, at 21:37:14

In reply to Re: Experiences w/ switching from SSRI to tricyclic? » Cam W., posted by Jane D on September 20, 2001, at 20:19:02

Jane - There should be no problem switching directly from an SSRI with a short half-life to a "serotonergic" TCA. That is, there should be no problem switching from Zoloft™ (sertraline) to Ethipramine™ (imipramine - Tofranil™).

There may have been some problem (mostly theoretical) in switching from Prozac™ (fluoxetine) to Ethipramine, as Prozac inhibits (stops the product of metabolizing enzymes) the cytochrome-P450-2D6 enzyme system AND has a very long half-life. Prozac would have slowed the CYP-2D6-enzyme from being produced, and since Ethipramine (Tofranil) is mainly metabolized by the 2D6-enzyme, Ethipramine would not be metabolized as readily as it would have, if the Prozac weren't present. The Prozac has a long elimination half-life (4 to 6 days at steady-state), so it lasts a long time in the body; thus may be able to artificially increase Ethipramine levels.

Having said that, even this interaction probably would not be significant, in the real world. The CYP-2D6-enzyme system is usually in a state of overabundance in the liver and, even after a short term inihibition by Prozac, there should be enough of the enzyme around to metabolize the Ethipramine.

Unless of course, you were a "poor metabolizer" (ie. had lower than normal levels of the CYP-2D6 enzyme; like 5% of the caucasian population).

Also, if you took Prozac and Ethipramine together, you would be at increased risk of serotonin syndrome, as well as increased risk of Ethipramine side effects (eg tachycardia, dry mouth, etc.). You may have to take a lower than normal dose of Ethipramine to avoid the TCA side effects.

Basically, this is another reason to be treated by a doctor. Instead of doing blood tests for Ethipramine, the doctor would watch for signs of TCA toxicity and serotonin syndrome (and hopefully also tell you what to watch for). Actually, most docs wouldn't put a patient on a TCA and Prozac, unless absolutely necessary, because it is a pain-in-the-ass to monitor.

To answer your first question: no it should be no problem switching from Zoloft to Ethipramine. Zoloft doesn't inhibit CYP-2D6 to any great extent and has a relatively short half-life (approx. 60h.).

Now, don't even ask me about going from an SSRI to a "noradrenergic" TCA (theoretically it is a problem with SSRIs; and may be with regular Effexor™ - venlafaxine).

Hopefully, I answered your second question, as well. The reason quick metabolizers would use Prozac to wean from Effexor (or Zoloft or Paxil or Luvox) is because of it's very long half-life. When you inhibit an enzyme system, there is less enzyme around to metabolize the drug. Quick metabolizers would have an overabundance of enzyme around.

I really hope that you can make something out of this mess. I really did try to be clear. - Cam


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poster:Cam W. thread:79138
URL: http://www.dr-bob.org/babble/20010917/msgs/79197.html