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Re: P450 Interactions? » jujube

Posted by zeugma on January 11, 2005, at 5:13:36

In reply to P450 Interactions?, posted by jujube on January 10, 2005, at 23:28:48

P450 is the enzyme system that breaks down most psychotropics, thus enabling them to be excreted in a timely way. Provigil is an inhibitor of cytochrome 2C19, which is the enzyme responsible for citalopram metabolism (the metabolites are inactive, I think). So adding Provigil will cause plasma levels of citalopram to rise, theoretically. This isn't such a big deal as citalopram doesn't have the cardiotoxicity issues of the TCA's, which are the major target of concern in these interactions (people have died as a result of SSRI-TCA interactions, and the system was unravelled in much the same way as serotonin syndrome was discovered: because people were dying for no good reason). I don't mean to alarm you. High citalopram levels aren't going to cause these problems. And Provigil itself is not cardiotoxic, as far as I know: it is nothing like Ritalin, which in high doses is causing problems, which have caused me to lower nortriptyline to 50 mg/day.

Remember, last summer I was on 100 mg nortriptyline plus up to 150 mg Provigil and 10 mg Ritalin, and was engaging in strenuous exercise every day (and I am someone who has not exercised for many years). The interaction I read about in Provigil's PI sheet, about a rise in clomipramine levels, is worrying (in fact, I think it's the reason he preferred me on Lexapro than Anafranil: less potential for cardiotoxicity) but even so with proper monitoring such a combination could be used. The effect of Provigil might be that you would have to lower your citalopram dosage because of increased SSRI side effects. Of course, Provigil likely counters some of those anyway.

-z


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