title: Economic consequences of selective serotonin reuptake inhibitor use with drugs also metabolized by the cytochrome P-450 system.
abstract: Administration of selective serotonin reuptake inhibitors (SSRIs) may increase plasma concentrations of concomitant medications that are also metabolized by the cytochrome P-450 system (CYP-450), in particular by the 2D6 and 3A4 isoenzymes. This may lead to side effects or other clinical events that might be expected to incur higher health-care expenditures. The purpose of this study was to assess whether there was a difference in expenditures during the first 90 days of SSRI therapy with paroxetine or sertraline versus fluoxetine in patients who were also receiving a stable dosage of a nonpsychiatric drug also metabolized by the CYP-450 2D6 or 3A4 isoenzyme systems. A sample of 2445 patients who initiated therapy with an SSRI while receiving a stable dosage of a nonpsychiatric drug was obtained from a private insurance claims database. Multivariate regression techniques were used to estimate total health-care expenditures in the first 90 days after receiving a prescription for an SSRI. After adjusting for nonrandom SSRI prescription patterns and controlling for observable and unobservable characteristics that might correlate with SSRI selection, total health-care expenditures were 95% higher for patients initiating SSRI therapy with sertraline or paroxetine compared with fluoxetine. Results suggest that there are cost differences between SSRIs during concomitant therapy with drugs also metabolized by the CYP-450 system. To determine whether there are additional differences in expenditures across SSRIs, future research should focus on (1) simultaneous initiation of SSRI therapy and a nonpsychiatric drug also metabolized by the CYP-450 enzyme system, and (2) addition of nonpsychiatric drug therapy to stable SSRI therapy. Relationships between additional expenditures, drug interactions, and clinical outcomes should also be assessed directly using medical records and patient interview data that are not available in claims-based files.
authors.affiliation: The MEDSTAT Group, Inc., Ann Arbor, Michigan, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ozminkowski
authors.forename: T R
authors.initials: TR
authors.lastname: Hylan
authors.forename: C A
authors.initials: CA
authors.lastname: Melfi
authors.forename: L M
authors.initials: LM
authors.lastname: Meneades
authors.forename: W H
authors.initials: WH
authors.lastname: Crown
authors.forename: T W
authors.initials: TW
authors.lastname: Croghan
authors.forename: R L
authors.initials: RL
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004358:Drug Therapy / Q000191:economics; D005260:Female; D005473:Fluoxetine / Q000378:metabolism / Q000627:therapeutic use; D005102:Health Expenditures; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D015999:Multivariate Analysis; D017374:Paroxetine / Q000378:metabolism / Q000627:therapeutic use; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000191:economics / Q000378:metabolism* / Q000627:therapeutic use*; D020280:Sertraline / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D005473:Fluoxetine; D006899:Mixed Function Oxygenases; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C104464:CYP3A protein, human