Differences in interactions of SSRIs
Brosen K
Department of Clinical Pharmacology,
Institute of Medical Biology,
Odense University, Denmark.
Int Clin Psychopharmacol 1998 Sep; 13 Suppl 5:S45-7


The SSRIs differ from each other with regard to their chemical structure, their pharmacokinetics and their potential for causing pharmacokinetic interactions through inhibition of species of the cytochrome P450 enzyme system. Cytochrome P450 (CYP) is a group of more than 30 different heme containing proteins in humans, some of which play a key role in the oxidation and hence the elimination of numerous drugs, including the SSRIs. Thus fluvoxamine, but not citalopram, fluoxetine, paroxetine and sertraline is a potent inhbitor of CYP1A2. Accordingly fluvoxamine has interactions with other drugs eliminated by CYP1A2 including caffeine, clozapine, olanzapine, theophylline, propranolol and tacrine. CYP2C19 is the source of the S-mephenytoin oxidation polymorphism. About 2% of whites are poor metabolizers in whom CYP2C19 is not expressed. Poor metabolizers have an impaired elimination of among other drugs citalopram. Although not metabolized by CYP2C19, fluvoxamine is still a potent inhibitor of the enzyme. The same applies to fluoxetine. CYP2D6 only makes up about 2-5% of the total P450 in the human liver, but anyway is the major enzyme catalyzing more than 30 clinically used drugs including all of the tricyclic antidepressants, several neuroleptics, opiates, betablockers, antiarrhythmics and among the SSRIs N-desmethylcitalopram, fluvoxamine, fluoxetine and paroxetine but not sertraline. All of the SSRIs inhibit CYP2D6 but fluoxetine, norfluoxetine and paroxetine are particularly potent inhibitors. CYP3A4 is the most abundant human cytochrome P450, but most of the SSRIs with the exception of norfluoxetine do not inhibit this enzyme, and interactions with SSRIs and CYP3A4 appear not to be a significant.

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