Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram

Citalopram is a selective serotonin reuptake inhibitor that is N-demethylat ed to N-desmethylcitalopram partially by CYP2C19 and partially by CYP3A4 an d N-desmethylcitalopram is further N-demethylated by CYP2D6 to the likewise inactive metabolite di-desmethyleitalopram. The two metabolites are not ac tive. The fact that citalopram is metabolised by more than one CYP means th at inhibition of its biotransformation by other drugs is less likely. Besid es citalopram has a wide margin of safety, so even if there was a considera ble change in serum concentration then this would most likely not be of cli nical importance. In vitro citalopram does not inhibit CYP or does so only very moderately. A number of studies in healthy subjects and patients have confirmed, that this also holds true in vivo. Thus no change in pharmacokin etics or only very small changes were observed when citalopram was given wi th CYP1A2 substrates (clozapine and therophylline), CYP2C9 (warfarin), CYP2 C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine and amitrip tyline) and CYP3A4 (carbamazepine and triazolam). At the pharmacodynamic le vel there have been a few documented cases of serotonin syndrome with cital opram and moclobemide and buspirone. It is concluded that citalopram is nei ther the source nor the cause of clinically important drug-drug interaction s, (C) 2001 Elsevier Science BY All rights reserved.