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Re: Combining Prozac and Imipramine?

Posted by Jim on April 11, 1999, at 16:53:21

In reply to Combining Prozac and Imipramine? , posted by Dave D. on April 9, 1999, at 8:46:32

Prozac *can* be combined with tricylics like
imipramine, often effectively, but be careful--
Prozac (like most SSRIs) can inhibit your body's
processing of tricyclics, causing more to build
up in your blood. Some studies have even found
Prozac to increase imip. levels by more than three
times, so I'd be very conservative with the
imipramine dose. (Even a low 25mg dose might end
up being more like 100mg with the Prozac!). It's
a good idea (and very simple) to get your blood
level checked to make sure that the imipramine
stays in normal range--perhaps both at the end of
the first week and a couple weeks later since the
build up can be gradual. See the article abstract
I pulled up for you below from Medline...
Good luck--with caution, the slight extra hassle
might be worth it.

Clin Pharmacol Ther 1992 Mar;51(3):239-48

Quantification and mechanism of the fluoxetine and tricyclic
antidepressant interaction.

Bergstrom RF, Peyton AL, Lemberger L

Lilly Laboratory for Clinical Research, Eli Lilly and Company, Indianapolis, IN 46285.

Clinical reports of concurrent use of fluoxetine and tricyclic antidepressant agents suggest that tricyclic concentrations increase
upon coadministration with fluoxetine. This study was conducted to confirm the clinical reports, to quantify the degree of
change in tricyclic kinetics, and to establish the mechanism of interaction. Twelve male subjects were given 50 mg desipramine
(six subjects) or 50 mg imipramine (six subjects) on three occasions: alone, after a 60 mg dose of fluoxetine, and after eight
daily 60 mg doses of fluoxetine. Fluoxetine significantly reduced oral clearance of both imipramine and desipramine as much as
tenfold and prolonged half-life as much as fourfold. Desipramine oral clearance values were 289, 112, and 27 L/hr alone, after
a single fluoxetine dose, and after multiple fluoxetine doses, respectively. Correspondingly, imipramine oral clearance values
were 181, 87, and 51 L/hr. These kinetic changes resulted in significantly higher plasma tricyclic concentrations after fluoxetine
administration. The amount of parent drug excreted unchanged in urine increased and imipramine or desipramine clearance to
their respective 2-hydroxy metabolites decreased. Metabolic conversion of imipramine to desipramine appeared to be
unaffected. The findings indicate that fluoxetine causes an inhibition of tricyclic 2-hydroxylation and may decrease first-pass
and systemic metabolism. When imipramine or desipramine are to be coadministered with fluoxetine, a lower dosage may be
needed to maintain steady-state concentrations and to avoid undesirable side effects caused by excessive tricyclic




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