The potential for clinically significant drug-drug interactions involving the CYP 2D6 system: effects with fluoxetine and paroxetine versus sertraline.

Background: Patients taking antidepressants are more likely to also be taking multiple medications, increasing the risk of adverse drug-drug interactions (DDIs). Because of substantial inhibition of one or more cytochrome P450 (CYP) enzymes at therapeutic doses, the selective serotonin reuptake inhibitors fluoxetine, fluvoxamine, and paroxetine have a higher risk of CYP-mediated DDIs than citalopram, escitalopram, and sertraline, which do not substantially inhibit any CYP enzyme.

Methods: Prescribing patterns in 2,779 Veterans Affairs (VA) patients who had a prescription for an antidepressant in the preceding year and a current prescription for at least one systemically active drug were analyzed to determine 1) prevalence of drug combinations with potential to cause CYP-mediated DDIs, 2) frequency of combinations of fluoxetine, paroxetine, or sertraline with drugs whose metabolism is principally dependent on CYP 2D6, and 3) use of reduced doses of CYP 2D6 substrate/drugs with narrow therapeutic indices in patients on fluoxetine or paroxetine compared with sertraline.

Complexity of medication use in the Veterans Affairs healthcare system: Part II. Antidepressant use among younger and older outpatients.

Context: A previous study, described in Part I of this report, found that 71% of a sample of 5,003 general outpatients in the Veterans Affairs healthcare system were receiving a unique drug regimen (i.e., total specific drug entities regardless of dose, formulation, or administration schedule).

Complexity of medication use in the Veterans Affairs healthcare system: Part I: Outpatient use in relation to age and number of prescribers.

Context: Multiple medication use is associated with an increased incidence of adverse drug-drug interactions (DDIs), medication errors, noncompliance, hospitalization, and healthcare costs. Drugs acting systemically or gastrointestinally ("SG" drugs) are of particular concern because of their potential to interact. A better understanding is needed of the relationship between multiple medication use, particularly of SG drugs, and age, number of prescribers, and common drug regimens.