Interactions of Serotonin Reuptake Inhibitors With Tricyclic Antidepressants

Clinically significant antagonistic interactions of the serotonin reuptake inhibitor (SRI) fluoxetine with the metabolic clearance of other drugs are well Known.1-4They include increases in circulating concentrations of tricyclic antidepressants (TCAs) by 100% to 500%.1,5Whether such interactions also occur clinically to a similar degree with other SRIs is less clear. Crewe and colleagues6found that several SRIs can interfere with the activity of a major drug-metabolizing pathway, the human hepatic microsomal cytochrome P-450-2D6 isozyme, in vitro. Paroxetine was most potent against the oxidation of a test agent, sparteine; fluoxetine and sertraline were slightly less active, whereas the experimental agents citalopram and fluvoxamine were weaker (inhibition constants of 0.15, 0.6, 0.7, 5.1, and 8.2 μl/L, respectively). Although these laboratory data are suggestive, clinical studies of the effects of SRIs other than fluoxetine on TCA metabolism are very limited. Despite an in vitro action of sertraline against the